Immunoassay developers stay current with new releases year round
By Steve Halasey
Every year, in vitro diagnostics (IVD) manufacturers launch scores of new and updated products designed especially for use in clinical laboratories. Naturally enough, many such products see their first market day at the annual meeting of the American Association for Clinical Chemistry (AACC), which this year will take place in Atlanta, July 26–30.
But neither IVD companies nor their customers go dormant in between AACC’s annual events, and many useful products often find their way to customers without first having a launch party on the show floor. By way of getting ready for this year’s AACC launches, in the sections that follow CLP looks back at some of the developments that have occurred in the field of immunoassays and related areas over the course of the past year.
In a time when many labs are considering whether to undertake the transition to an individualized quality control (QC) plan, it’s natural that the utility of calibrators and controls is much on their mind. In November 2014, global diagnostics firm Randox, Crumlin, UK, responded to market interest by launching its Acusera Liquid Immunoassay Premium Plus Control, a third-party, multianalyte control eagerly anticipated by clinical laboratories.
Combining over 50 analytes within one control, Acusera Liquid Immunoassay Premium Plus is designed to simplify QC by reducing the number of individual controls required by the laboratory. The control includes clinically relevant levels of tumor markers, cardiac markers, therapeutic drugs, hormones, and vitamins—including vitamin D.
Liquid Immunoassay Premium Plus is a fully commutable control, which is essential for immunoassay testing. Using commutable controls with a matrix similar to patient samples reduces antibody cross-reactivity and decreases the risk of control values shifting when a reagent batch is changed. The control offers a number of useful features:
- Liquid for ease of use.
- Includes routinely run tumor markers as well as N-terminal pro-B-type natriuretic peptide, parathyroid hormone, troponin I, troponin T, and vitamin D.
- Stable to expiry date at –20 to –70°C.
- Open vial stability of up to 7 days at +2 to +8°C.
- Available in control levels 1, 2, and 3 in 5 ml vials.
“We are delighted to bring to market a product which will help laboratories significantly streamline QC in immunoassay testing, while ensuring accurate patient testing,” said David Hunter, global business manager for Randox Quality Control. “As laboratory budgets are increasingly under pressure, consolidated QC products offer major savings in both preparation time and money.”
In December 2014, Ortho-Clinical Diagnostics Inc, Raritan, NJ, announced the nationwide availability to hospitals of the Nephrocheck test system, a first-of-its-kind test designed to help healthcare providers identify patients at risk of developing moderate or severe acute kidney injury (AKI) within 12 hours of assessment.
AKI is a common, costly, and potentially fatal complication among hospitalized patients. In comparing patients with AKI to patients without AKI, hospital and intensive care unit (ICU) lengths of stay double, as do costs of care and readmission rates. Moreover, death rates at 1 year are higher among patients with AKI alone, compared to those patients with heart attack alone. Identifying risk of AKI is paramount because AKI usually lacks signs and symptoms and can potentially result in irreversible kidney damage if recognition is delayed. The guidelines published by the foundation, Kidney Disease Improving Global Outcomes, recommend that patients be assessed for risk of AKI to protect their kidney function.1
“The availability of a test to identify patients at risk of developing moderate to severe acute kidney injury can allow for the recognition and closer management of these patients,” said Kianoush Kashani, MD, a nephrologist at the Mayo Clinic, Rochester, Minn.
The Nephrocheck test result, called the AKIRisk score, has significant ability to distinguish patients with AKI from those without AKI. To calculate the score, the test system measures the concentrations of two urinary biomarkers using the Astute 140 meter. Discovered and validated through large multicenter clinical studies, the two novel biomarkers—tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor binding protein 7 (IGFBP7)—are thought to be involved in G1 cell cycle arrest in the earliest phases of injury.
In July 2014, Ortho-Clinical Diagnostics entered into a strategic collaboration with Astute Medical Inc, San Diego, the developer of the Nephrocheck test system, to become the exclusive sales agent for Astute Medical’s Nephrocheck test and the Astute 140 meter in the United States and in certain countries of the European Union.
Not to be outdone, in January 2015 bioMérieux, Marcy l’Etoile, France, signed a global, semi-exclusive agreement with Astute Medical, and obtained a license to develop, produce, and market the Nephrocheck test for use on its own line of immunoassay analyzers, the Vidas, mini Vidas, and Vidas 3.
“This agreement aligns with our business strategy of bringing novel biomarkers with high clinical value to market through a variety of testing platforms,” commented Chris Hibberd, Astute Medical CEO. “This is great news for customers, as it will increase global market availability and offer a range of platform capabilities to suit laboratory needs.”
At the beginning of January 2015, FDA granted premarket notification (510(k)) clearance to Beckman Coulter Diagnostics for the company’s Access 25(OH) Vitamin D Total assay. Designed for use on the company’s Access 2 and UniCel DxI series of immunoassay systems, the new assay is an important addition to the company’s bone metabolism assay menu.
“FDA clearance of our 25(OH) Vitamin D Total assay allows us to provide laboratories with the tools needed to confidently diagnose and manage vitamin D deficiency-related diseases,” said Arnd Kaldowski, president, Beckman Coulter Diagnostics. “The new assay delivers increased accuracy in patient results through traceability to the gold standard 25(OH) vitamin D reference measurement procedure (RMP) from Ghent University, and equimolar detection of 25(OH) vitamin D2 and 25(OH) vitamin D3.”
The Ghent RMP is the reference procedure utilized by the Vitamin D Standardization Program, an international collaboration established by the Office of Dietary Supplements at the National Institutes of Health, with the goal of promoting standardized laboratory measurements of 25(OH) vitamin D around the world.
The new assay also provides excellent stability, greater ease of use, and convenient storage through innovative new packaging designed to prevent light-induced reagent degradation. Laboratories will also benefit from the speed and flexibility provided by the company’s numerous instrumentation options, including the UniCel DxI 800, the industry’s highest throughput immunoassay analyzer.
Since the development of the earliest kits, clinicians have relied on urine-based tests to determine whether a woman is pregnant. But collecting a sample from a woman in an emergency setting can be difficult, especially if she is dehydrated, in pain, or even unconscious. In April, Abbott, Abbott Park Ill, addressed this challenge with a first-of-its-kind blood test for detecting human chorionic gonadotropin (hCG), the hormone that is usually used to determine whether a woman is pregnant.
“During a medical emergency, every minute matters,” said Scott Pennington, RN, BSN, director of critical care services at Gulf Coast Regional Medical Center, Panama City, Fla. “A fast blood test to help determine if a woman is pregnant can help doctors and nurses quickly decide appropriate care, which could potentially save lives.”
Performed on Abbott’s i-Stat system, a handheld, portable blood analyzer, the i-Stat Total ?-hCG test requires just two to three drops of blood, and provides high-quality results within 10 minutes. Granted premarket notification (510(k)) clearance by FDA, the test can detect if a woman is in the early stages of pregnancy by measuring very low levels of hCG in blood or plasma.
“In today’s health care environment, clinicians are faced with a growing number of people who are seeking care,” said Sharon Bracken, Abbott vice president for point-of-care diagnostics. “Abbott’s ?-hCG blood test serves as a new tool to help physicians determine pregnancy status quickly and accurately, right at the bedside, to help provide quality treatment.”
In April, Beckman Coulter’s Access AccuTnI+3 troponin I blood test got a boost when the test was used in a study to identify the precise magnitude of change in cardiac troponin required for early diagnosis of a heart attack. The Access AccuTnI+3 troponin I blood test is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma using the company’s Access 2 immunoassay system or UniCel DxI Access immunoassay system.
Clinical guidelines for diagnosis of myocardial infarction require demonstration of a rise and/or fall in the values of troponin (a protein released from damaged heart cells and detected in the blood) between samples collected in sequence following presentation to the emergency department. However, the guidelines do not quantify what constitutes a clinically significant rise and/or fall.
Published as two companion articles in a special cardiac biomarkers issue of Clinical Biochemistry, the results of the study recommended movement away from the frequently used percentage-change reading in favor of using an absolute difference by ng/mL change.2,3 The study demonstrated that absolute changes (0.01 or 0.02 ng/mL) performed significantly better than relative (percentage) changes at all time intervals after emergency department admission.
“Study results suggest that the majority of patients with myocardial infarction can be identified at earlier observation times, and support consensus recommendations for an optimal blood sampling protocol with troponin measurement on admission and three hours later,” said principal investigator and lead author Alan B. Storrow, MD, vice chairman for research and academic affairs in the department of emergency medicine at Vanderbilt University. “Another key finding of the study is that rule-out (correct identification of patients without a heart attack) was nearly 100% when baseline troponin was less than the diagnostic threshold of 0.03 ng/mL and absolute delta troponin was less than 0.01 ng/mL.”
“As troponin values rose, the probability of myocardial infarction increased,” said Paula Southwick, PhD, coauthor and principal clinical research scientist at Beckman Coulter Diagnostics. “Baseline troponin values greater than 0.20 ng/mL were associated with nearly 90% probability of myocardial infarction. Earlier rule-in and rule-out may potentially save patient lives.”
In May, Thermo Fisher Scientific, Carlsbad, Calif, announced that it had developed a new, automated system for processing western blots. Based on the company’s proprietary sequential lateral-flow (SLF) technology, the new iBind Flex Western system is designed to enable a more versatile walkaway solution for the immunodetection step in a western blotting workflow.
Compatible with downstream chemiluminescent, colorimetric, or fluorescent detection protocols, and optimized for higher sensitivity and reproducibility, there is potential for a significant reduction in primary antibody required when compared to manual blot processing.
“We are thrilled to introduce the next-generation iBind Flex device and consumables to address a latent need that affects a large segment of life science researchers worldwide who frequently perform western blotting,” said Kevin Lowitz, senior product manager of protein biology for Thermo Fisher Scientific. “It’s a unique opportunity to develop a product that offers improved convenience and performance with the added benefit of being a cost-effective alternative to both fully automated platforms and traditional manual methods.”
Experimental results can be achieved without the need for power, pumps, or vacuums through the use of SLF technology, which is designed to automate the blocking, primary and secondary antibody binding, and washing steps for immunodetection of proteins transferred to a nitrocellulose or polyvinylidene fluoride membrane. The sequential and uniform flow of solutions across a glass fiber matrix ensures a consistent antigen-antibody interaction to deliver robust protein detection.
“While genomics has garnered much of the attention from the scientific community, researchers will continue to rely on proteomics tools to better understand the biological impact proteins have on disease,” said Mark Stevenson, executive vice president for Thermo Fisher Scientific. “Western blotting is a proven, yet time-consuming and error-prone method for protein analysis. Through our continued commitment to innovating in this space, the iBind Flex Western system’s intuitive design automates immunodetection and enables researchers to achieve more reproducible results.”
Diagnostics companies have become increasingly engaged in activities directly at addressing the global challenge of antibiotic resistance. Accelerate Diagnostics Inc, Tucson, is an in vitro diagnostics company whose approach to the challenge utilizes a proprietary process with both genomic and phenotypic detection technologies that significantly decrease the time to result while achieving high sensitivity and specificity.
In June, Accelerate announced that it had been granted a CE mark for in vitro diagnostic use of its lead product, the Accelerate ID/AST system, a diagnostic platform that provides rapid identification and antimicrobial susceptibility testing of serious infections. The company also announced that it had initiated enrollment at eight clinical trial sites for its preclinical study, which will be followed by an FDA registration trial. The company expects to launch an FDA-cleared version of the product in the United States during the first half of 2016.
At the end of June, bioMérieux, Durham, NC, launched two new FDA-cleared tests that promise to detect Lyme disease in just 27 minutes. An infection caused by the bacterium Borrelia burgdorferi, which is transmitted through the bite of an infected tick, Lyme disease initially causes a distinctive rash, flu-like symptoms, fever, fatigue, and joint pain. Later symptoms can include fatigue, arthritis, and chronic neurological problems.
Performed on bioMérieux’s Vidas and mini Vidas automated immunoassay platforms, the new Vidas Lyme IgG II and Vidas Lyme IgM II assays provide rapid and differential detection of Borrelia burgdorferi infection and allow classification of the infection in early or late stages of the disease. The tests make use of innovative recombinant proteins that produce the sensitivity and specificity needed to detect all of the main disease-causing Borrelia strains, and to reduce cross-reactivity to other infectious diseases. Because they detect IgM and IgG antibodies separately, the new assays reduce the number of confirmatory tests needed, potentially reducing cost.
According to Lena Prisco, PhD, medical operations director at Vineyard Medical Care, Vineyard Haven, Mass, using the assays to measure IgG and IgM antibodies separately, as a screening test, provides the ability to quickly distinguish early from late infection. “Having this information earlier decreases unnecessary or inappropriate treatment for previous infections, and provides earlier information aiding differential diagnosis in endemic areas of tick borne disease,” she says.
“BioMérieux is committed to helping healthcare professionals diagnose infectious diseases, including Lyme disease,” says Samuel Bozzette, MD, PhD, vice president of medical affairs for bioMérieux Americas. “The new tests, in conjunction with clinical information, will help clinicians prescribe the appropriate treatment adapted to the patient’s infection status.”
NEXT STOP, ATLANTA
While manufacturers of finished diagnostics typically dominate the exhibit hall at AACC’s annual meeting, suppliers of test-ready biological raw materials also make up a significant proportion of the exhibitors. This year, BBI Solutions, Cardiff, UK, will be exhibiting at its 25th consecutive AACC meeting, presenting the company’s complete range of high-quality biological raw materials, assay development expertise, and innovations in assay manufacturing services. The company will also be showcasing a number of products new to its lineup:
- High purity intrinsic factor—a critical reagent in vitamin B12 assays—a high performing product with stable supply that meets a specific need in the market.
- Next-generation FAD-GDH with reduced xylose interference, a new enzyme to meet the growing demands of accuracy in blood glucose monitoring. This new enzyme joins BBI’s market-leading glucose oxidase and first-generation FAD-GDH.
- For the early diagnosis of acute kidney injury, a new recombinant neutrophil gelatinase-associated lipocalin protein that has low dimer content and >96% purity, with a faster response time compared to other standard biomarkers.
“Using high-quality raw materials really does make a difference when trying to optimize the performance of your assay,” explains Simon Packer, technical manager at BBI. “In an industry with tightening regulatory requirements, the need for accurate results is essential.”
Steve Halasey is chief editor of CLP. He can be reached via [email protected].
- Kidney Disease Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013; 3(1):1–150; doi: 10.1038/kisup.2012.74.
- Storrow AB, Christenson RH, Nowak RM, et al. Diagnostic performance of cardiac troponin I for early rule-in and rule-out of acute myocardial infarction: results of a prospective multicenter trial. Clin Biochem. 2015;48(4–5):254–259; doi: 10.1016/j.clinbiochem.2014.08.018. Epub September 4, 2014.
- Storrow AB, Nowak RM, Diercks DB, et al. Absolute and relative changes (delta) in troponin I for early diagnosis of myocardial infarction: results of a prospective multicenter trial. Clin Biochem. 2015; 48(4–5):260–267; doi: 10.1016/j.clinbiochem.2014.09.012. Epub September 28, 2014.