Feature Articles

Published: October 24, 2012
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The Year in IVDs

Industry giants and smaller players launched IVD products and technologies this past year aimed at improving automation, decreasing operator involvement, offering point-of-care analysis, decreasing time to test result, and more.

By: Maureen Kingsley

Anyone keeping an eye on the IVD industry during the past 12 months or so could likely rattle off a series of significant developments: Roche’s failed attempt to acquire Illumina might top one’s list of notable IVD news, or possibly Hologic’s recent acquisition of Gen-Probe. New partnerships between IVD and pharmaceutical companies forged in pursuit of drug-diagnostic test combinations-Dako and Genentech, Abbott and Merck, and Ventana Medical Systems reaching out to several different pharma firms-increased in number this past year. FDA, encouragingly, appears to remain interested in optimizing the regulatory process for companion diagnostics.
The past year also ushered in numerous IVD regulatory approvals, both here and in Europe, for products aimed at increasing automation, decreasing complexity of use, empowering patients to take charge of their healthcare, harnessing the power of molecular diagnostics, and personalizing medicine for the benefit of all stakeholders. A selection of those, and other noteworthy IVD-related products, arranged by category, is presented here.

Instrumentation

Siemens Healthcare Diagnostics introduced its new clinical laboratory automation platform during an early morning press conference at the AACC 2012 Clinical Lab Expo on July 18. The platform, dubbed Aptio Automation, is described by the company as a “transformational technology” that combines smooth workflow with peak performance, adaptability, and intelligent technology.
By 2014, it’s estimated that the United States alone will need 81,000 additional medical technologists and technicians to replace retiring staff, plus 68,000 more to fill newly created positions, according to a business study from g2reports.com. All of this makes a compelling case for increased clinical lab automation and, Siemens hopes, interest in the Aptio system.
Dave Hickey, CEO of Siemens’ Chemistry, Immunoassay, Automation and IT Diagnostics business unit, cited a number of the Aptio’s attributes including its adaptability to testing needs and floor space, modularity, and formidably intelligent IT. The latter is a “key underpinning because it optimizes flow, sets priorities, and autoverifies results,” Hickey added. Centralized IT provides comprehensive analytics, and the system maintains the flexibility to provide pre- and postanalytical capabilities.
This past spring another IVD leader, Abbott, announced it had obtained CE mark approval to market its rapid, high-throughput PLEX-ID instrument along with three assays for use on the system: PLEX-ID Viral IC Spectrum, PLEX-ID BAC Spectrum BC, and PLEX-ID Flu. (The PLEX-ID Viral IC Spectrum assay is designed to detect and identify 11 viral families with more than 250 species of important systemic viral pathogens, including herpes simplex virus, cytomegalovirus, Epstein-Barr virus, and others. The PLEX-ID BAC Spectrum BC assay can detect and identify nearly 400 species of bacteria, as well as the presence of genetic markers that determine bacterial resistance to certain antibiotics. The PLEX-ID Flu assay detects and identifies known influenza A viruses, newly emerging influenza A strains, and influenza B.)
PLEX-ID, which is based on molecular diagnostic technologies, offers rapid detection and identification of the infection-causing microbes for which it tests. It provides results in less than eight hours-an improvement over the days or weeks required for traditional culture methods.

Molecular Diagnostics

The Centers for Disease Control and Prevention developed a new diagnostic test to detect the presence of dengue virus in people with symptoms of dengue fever or dengue hemorrhagic fever. The CDC DENV-1-4 Real Time RT PCR assay has been authorized by FDA for use in the United States and can be performed using equipment and supplies many public health laboratories already use to diagnose influenza.
The new test will help diagnose dengue within the first seven days after symptoms of the illness appear. It can identify all four dengue virus types. This is the first FDA-approved molecular test for dengue that detects evidence of the virus itself. The other available FDA-approved test detects a certain type of antibody (immunoglobin M class antibodies) to dengue virus.  
“The need for the new dengue diagnostic test was high,” said Jorge L. Munoz-Jordan, PhD, chief of Molecular Diagnostics and Research at the CDC Dengue Branch.
The new test is available to clinical and public health laboratories within the United States and internationally. Kits became available for distribution beginning this July.
Also in molecular diagnostics, FDA approved the PROGENSA PCA3 (prostate cancer gene 3) assay by Hologic Gen-Probe. This assay bears the distinction of being the first urine-based molecular test to help determine the need for repeat prostate biopsies in men who have had a previous negative biopsy.
“Overexpression of the PCA3 gene is highly specific to cancerous prostate tissue,” said John Wei, MD, MS, Professor of Urology at the University of Michigan Health System. “When evaluated with other risk factors, the PROGENSA PCA3 assay fills an important unmet clinical need by helping physicians identify which men suspected of having prostate cancer should undergo a repeat prostate biopsy.”
The assay is indicated for use in conjunction with other patient information to aid in the decision for repeat biopsy in men 50 years of age or older who have had one or more previous negative prostate biopsies and for whom a repeat biopsy would be recommended by a urologist based on the current standard of care, before consideration of PROGENSA PCA3 assay results. A negative PROGENSA PCA3 assay result is associated with a decreased likelihood of a positive biopsy. A prostate biopsy is required to diagnose cancer.
The test has received regulatory approval from and is available for sale in the United States, Canada, and the European Union.

Assays

Idaho Technology Inc., a privately held clinical diagnostics company that provides instruments for pathogen identification and DNA analysis, announced FDA clearance of five additional pathogens for its FilmArray Respiratory Panel (FilmArray RP), a multiplex pathogen-detection system. This brings the total to 20 viral and bacterial respiratory pathogens for which FilmArray RP is now cleared. The additional five pathogens are Bordetella pertussis, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Coronavirus 229E, and Coronavirus OC43.   
With the addition of these pathogens, the respiratory panel now includes the first FDA-cleared assays for eight of the 20 organisms on the panel. Furthermore, the FilmArray RP is the only FDA-cleared panel capable of distinguishing between certain bacterial and viral respiratory infections. This represents a significant advance in the field of infectious disease detection.   
Another standout company in the realm of assay development this past year is Fujirebio Diagnostics, which specializes in oncology biomarker assays. Fujirebio announced FDA clearance to market its HE4 test in an algorithm called ROMA (HE4 EIA + ARCHITECT CA 125 IITM) to aid in assessing whether a pre- or postmenopausal woman with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery.   
The risk of ovarian malignancy algorithm (ROMA) test uses the results from simple blood tests, CA125 and HE4, to identify patients presenting with adnexal mass as high or low likelihood for finding malignancy on surgery. HE4 has been shown to be elevated in epithelial ovarian cancers, the most common type of ovarian cancer.  ROMA is a qualitative serum test that combines the results of HE4 EIA, ARCHITECT CA 125 II, and menopausal status into a numerical score.
 “Using ROMA with HE4 and CA125 significantly improves our ability to identify women who are at high or low likelihood of having ovarian cancer when they present with an ovarian cyst or mass,” said Richard G. Moore, MD, Associate Professor of Obstetrics and Gynecology at the Alpert School of Medicine at Brown University and Director of the Center for Biomarkers and Emerging Technologies in the Program for Women’s Oncology at Women and Infants’ Hospital in Providence, RI. “Patients who have ovarian cancer have better outcomes when their surgery is performed by a gynecologic oncologist at centers experienced in the management of this disease. This combination test will allow physicians to identify those patients who should be treated by a gynecologic oncologist, and, equally important, allow women with benign disease to stay in their communities with the physician who knows them best. It will change the way doctors diagnose and treat ovarian cancer,” added Moore, who is the lead researcher for the team that developed ROMA and author of two multicenter studies investigating the use of HE4 and CA125 and ROMA.  
Ortho Clinical Diagnostics Inc. (OCD) made news with its announcement of the availability of the Avioq HTLV-I/II Microelisa

The Avioq HTLV-I/II Microelisa System assay
The Avioq HTLV-I/II Microelisa System assay

System assay, a new test developed in partnership with Avioq Inc. to screen blood and organ donations for antibodies to human T-lymphotropic virus (HTLV) type I and II. HTLV is a retrovirus that falls within the same biological category as HIV. Screening for antibodies to HTLV-I/II is required by FDA for the nearly 16 million blood donations collected in the United States each year. HTLV, if left undiagnosed, may cause such conditions as a rare form of leukemia and neurological diseases.
The AVIOQ HTLV-I/II Microelisa System assay is fully compatible with the ORTHO Summit System platform. “By providing a fast, cost-effective, and reliable screening method for antibodies to HTLV type I and II, OCD is enhancing the donor screening community’s ability to adhere to FDA’s testing guidelines, while at the same time protecting patients who receive blood and plasma donations,” said Paul Contestable, Principal Scientist, OCD.
Responding to the introduction of a relatively new entrant to the illegal-drug market, British forensic and clinical toxicology company Randox Technology developed two ELISA kits this year for the forensic detection of so-called “bath salts,” illegal recreational drugs quickly penetrating the international market. Ivory Wave, Ocean Snow, and Cloud Nine are commercial names for Mephe-drone, MDPV, and other drugs belonging to the synthetic cathinones family. Randox’s Mephedrone ELISA offers a highly sensitive screen targeting Mephedrone HCl, R(+)-Methcathinone HCl, Flephedrone HCl, Methcathinone, 3-Fluoromethcathinone (3-FMC), and additional metabolites. The Randox Toxicology MDPV ELISA targets MDPV, MDPBP, and Naphyrone HCL. The kits can accurately screen both urine and blood.
Historically, the only detection method for bath salts has been expensive and complicated chromatographic screens.
Focusing on an entirely different IVD market than Randox, German company ORGENTEC Diagnostika has developed four new laboratory tests for the diagnosis of autoimmune liver diseases. These tests, which are based on ELISA technology and were specifically developed for fully automated analysis with Alegria, are commercially available in the European Union, and available as RUO products in the United States.
The new test systems, called Anti-Sp100, Anti-gp210, Anti-LKM-1, and Anti-SLA, reliably detect specific autoantibodies that are characteristic of various autoimmune liver diseases. For the first time, these newly introduced laboratory tests allow for the individualized, rapid, and fully automated detection of the corresponding auto-antibodies.
Abbott’s genetic test for acute myeloid leukemia prognosis was also cleared by FDA this past year. The new test, based on FISH technology, detects chromosomal abnormality to help predict the prognosis of patients with acute myeloid leukemia (AML), one of the most common types of leukemia in older adults.
The Vysis EGR1 FISH Probe Kit, which happens to be the third Abbott FISH assay approved or cleared by FDA for oncology applications in a narrow timeframe, detects a chromosomal deletion in bone marrow that is usually associated with an unfavorable prognosis for AML patients.
“Abbott’s Vysis EGR1 FISH Probe Kit can identify which AML patients have the chromosomal abnormality upon diagnosis and provides physicians with another clinically validated tool to assess a patient’s overall prognosis,” said Stafford O’Kelly, head of Abbott’s molecular diagnostics business.
Featured at this year’s Clinical Lab Expo, Thermo Fisher Scientific’s QMS Tacrolimus assay updates the technology used to monitor tacrolimus, the most commonly prescribed immunosuppressant drug. The test is not yet available in the United States but earned the CE mark during the past year.
The liquid, ready-to-use immunoassay provides bar-coded system reagents to run on the Thermo Scientific Indiko benchtop analyzer. Applications are also available for mainframe, high-throughput systems such as the Beckman Coulter AU Series, Roche’s cobas, and OCD’s Vitros systems. This assay completes an update of the company’s full menu of immunosuppressant immunoassays, which includes cyclosporine, everolimus, and mycophenolic acid.
Based on the Thermo Scientific Quantitative Microsphere Systems (QMS), a homogeneous particle-enhanced turbidimetric technology, the immunoassay provides improved low-end sensitivity to aid physicians in monitoring patients on multiple drug therapies.

Companion Diagnostics

FDA approved Zelboraf (vemurafenib) for the treatment of BRAF V600E mutation-positive inoperable or metastatic melanoma, as determined by its FDA-approved companion diagnostic test, the cobas 4800 BRAF V600 Mutation Test. Roche’s test identifies patients eligible for treatment with Zelboraf. (Zelboraf is the first and only FDA-approved personalized

Cobas 4800 BRAF V600 Mutation Test
Cobas 4800 BRAF V600 Mutation Test

medicine shown to improve survival in people with BRAF V600E mutation-positive metastatic melanoma. It is designed to target and inhibit some mutated forms of the BRAF protein found in about half of all cases of melanoma, the deadliest and most aggressive form of skin cancer.)
“FDA approval  of the Cobas 4800 BRAF V600 Mutation Test was an important milestone in the delivery of companion diagnostics to the marketplace,” said Steven Binder, director, Technology Development at Bio-Rad Laboratories. He continued: “FDA released a draft guidance document in July 2011 to facilitate the development and review of these products, but an approval is far more influential than a guidance document. It shows diagnostic manufacturers and reference labs that what seemed difficult or impossible yesterday can become routine tomorrow.”

Point of Care

Roche made strides in point of care in addition to companion diagnostics, as evidenced by FDA’s approval of the cobas b 123 POC system this year. This mobile blood gas analyzer was designed for hospital point-of-care settings. Using this instrument, healthcare professionals can perform on-the-spot assessment of a patient’s oxygenation levels and electrolyte balance, among others. With seamless connectivity to the IT environment, wirelessly or via a network port, the cobas b 123 POC system uses Roche’s POC data-management systems-cobas bge link software and the cobas IT 1000 application.
Featuring a patented thick-film sensor technology and a broad assay menu that includes lactate testing, the cobas b 123 POC system offers quick results for 15 critical-care blood gas and electrolyte tests, with a turnaround time of two minutes. Its mobile cart installation facilitates flexible use in various areas, including the laboratory and the intensive care unit.
The cobas b 123 POC system won a Gold Medical Design Excellence Award and the Red Dot Design Award for excellent product design in medical care in 2011.
Sphere Medical Holding plc, a developer of monitoring and diagnostic products for the critical-care setting, announced CE-marking of its Pelorus 1500 IVD device.

The Pelorus 1500
The Pelorus 1500

The Pelorus 1500 bills itself as the world’s first point-of-care IVD medical device for the rapid measurement of the concentration of the intravenous anaesthetic propofol in blood samples and has been developed specifically for anesthetists in the critical-care setting. The device allows anesthetists to know the actual rather than predicted concentration of propofol, allowing the personalization of dosing to the patient.
Propofol is one of the most widely used intravenous anesthetics. Monitoring of inhaled anesthetic gases is already a standard of care, but there is no equivalent measurement used for intravenous anaesthetics such as propofol. Sphere Medical expects the Pelorus 1500 to be used in conjunction with existing dosing pumps.

Home Health

In July of this year, the first and only rapid OTC HIV test was approved for marketing in the United States. The test, manufactured by OraSure Technologies Inc., can detect antibodies to both HIV-1 and HIV-2 with an oral swab, providing confidential in-home testing with results in about 20 minutes. It is an over-the-counter version of the company’s OraQuick ADVANCE HIV 1/2 Antibody Test. OraSure Technologies made considerable history with this product: it is the first rapid diagnostic test for any infectious disease that has been approved by FDA for sale over the counter.
 

The OraQuick In-Home HIV Test
The OraQuick In-Home HIV Test

“Approval of the OraQuick In-Home HIV Test represents a major breakthrough in HIV testing,” said Douglas A. Michels, President and CEO of OraSure Technologies. “For the first time ever, individuals will have access to an in-home oral test that will empower them to learn their HIV status in the comfort of their homes and obtain referral to care if needed. This new in-home rapid test-the same test doctors have been using-will help individuals at risk for HIV who otherwise may not test in a professional or clinical setting.”
Heather Thompson, editor of MD+DI magazine and website (a sister brand of IVD Technology), points to the “marvelous” packaging of the at-home test as a leading reason for its success and FDA approval. “Inside an unassuming box is a thermoformed clamshell package,” she wrote of OraQuick’s packaging in a blog post. “It contains a flipbook that guides the reader through the testing package, several pamphlets, and two foil-wrapped pieces containing the diagnostic. The patient never leaves the package behind during test taking. Thermoformed shelves on the inner lid of the main package hold the diagnostic oral swab upright while the assay runs.”
The flipbook provides step-by-step instructions, Thompson adds, including a flap that the user places over the test while it is running.
 At press time, the OraQuick In-Home HIV Test was expected to be available for purchase this October at more than 30,000 retail outlets throughout the country and online.
In the spirit of improving, digitizing, and personalizing blood-glucose monitoring, Abbott announced FDA clearance of the FreeStyle InsuLinx Blood Glucose Monitoring System, the first from Abbott to include a touch screen interface, an automated logbook, and several personalization features designed to improve diabetes management for patients. The device is also

The FreeStyle  InsuLinx blood glucose monitoring system
The FreeStyle InsuLinx blood
glucose monitoring system

equipped with built-in FreeStyle Auto-Assist software that enables patients to track progress, analyze trends, and easily display data for their healthcare providers.

Looking Ahead

These products represent just a sampling of introductions to the IVD market this past year. The next 12 months are likely to see additional expansions of existing multiplex tests, more companion diagnostics earning regulatory approval, and continued focus on both point-of-care and home-health devices. One could reasonably assume that molecular diagnostics will continue to play a greater role in IVD testing as well.
As IVD manufacturers continue to deliver on the promise of creating ever-better diagnostics, IVD Technology will be here to take note of their progress.

 


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