Originally Published in IVD Technology October 2005
This Year in IVDs
IVD manufacturers continued to develop and launch an assortment of sophisticated new products and technologies in 2005.
For the IVD industry, the past year was fraught with both encouragement and frustration.
In one promising development, FDA released a final guidance on pharmacogenomic data submissions and a preliminary concept paper on drug-diagnostic codevelopment. By publishing these documents, the agency has given the impression that it is setting the stage for anticipated advances in personalized medicine. Such a move lays the groundwork for further developments in molecular diagnostics and greater collaborations between IVD manufacturers and pharmaceutical companies.
A report released by AdvaMed (Washington, DC), however, noted the grave deficiencies in reimbursement levels for IVDs. It is hoped that policymakers will take notice of this issue and make the appropriate adjustments and changes in reimbursement that reflect the value that IVDs contribute to healthcare. If such changes are made, IVD manufacturers could expect greater returns, which could lead to the development of even better diagnostic tests.
Such policy shifts may take a few years to fully affect the IVD industry. For now, IVD manufacturers have continued to take advantage of a recovering market by releasing faster, more-accurate, and more-effective diagnostic devices. This article examines some of the key segments of the IVD industry, highlighting new product launches and trends in each area.
Instrumentation and Automation
An ongoing clash has emerged between IVD manufacturers and the Centers for Medicare and Medicaid Services (CMS) over the appropriateness of alternative internal control processes in automated laboratory instruments. Although FDA has cleared such processes, CMS has determined that they do not meet the quality control (QC) requirements under the Clinical Laboratory Improvement Amendments (CLIA). Some affected manufacturers whose instruments had already undergone an intensive premarket review with FDA became entangled in technical noncompliance issues related to CLIA QC requirements.
Consequently, CMS began an initiative to modify the CLIA QC requirements and allow labs to use equivalent QC, which is significant for IVD manufacturers of automated instruments that have self-monitoring features and built-in controls. The new regulations would allow labs to reduce the amount of QC if an instrument monitors all or part of the testing processes, and provided that users can demonstrate the reduced QC is adequate. With manufacturers trying to figure out how to capitalize on this exemption, future automated instruments and systems will likely be designed and marketed to take the QC burden off the lab’s shoulders.
Abbott Laboratories (Abbott Park, IL) received 510(k) clearance from FDA for its Cell-Dyn Sapphire, an automated high-volume hematology instrument that incorporates monoclonal antibody tests for additional cellular analysis. This instrument’s blue diode laser offers fluorescence and multiangle polarized scatter separation technology to provide analysis of red blood cells, white blood cells, and platelets. With its monoclonal antibody tests, the Cell-Dyn Sapphire also provides common flow cytometry capabilities, allowing some tests to be performed in the hematology laboratory versus being sent out to a specialized lab for processing.
Bayer Diagnostics (Tarrytown, NY) introduced its Rapidlab 1200 analyzer, a critical-care blood gas instrument. This automated high-throughput device offers a comprehensive test menu, including pH, blood gas, electrolytes, metabolites, and CO oximetry. Additional features of the Rapidlab 1200 system include onboard automatic quality control materials that are independent from internal instrument calibrators. This quality control feature improves country-specific regulatory compliance initiatives and simplifies quality control processes.
Beckman Coulter Inc. (Fullerton, CA) launched its UniCel DxC 800 Synchron clinical system, the third in the company’s series of new UniCel-brand laboratory instruments. This instrument reflects the company’s ongoing strategy to deliver standardized product lines with large onboard test menus for greater workstation consolidation. The DxC 800 can be configured with Beckman’s closed-tube sampling technology and can perform automated serum indices. This device also features automatic stat notification, rerun of samples with abnormal results, review-by-exception, and work-pending log. In addition, the DxC 800 can be configured with a near-infrared particle immunoassay detection system that operates at a 940-nm wavelength.
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| bioMérieux: The Vitek 2 Compact is an automated bacterial identification and antibiotic susceptibility testing system that detects changes in organism growth under various media and antibiotic concentrations. |
bioMérieux Inc. (Durham, NC) released its Vitek 2 Compact, an automated bacterial identification and antibiotic susceptibility testing system that is designed for small to mid-sized microbiology laboratories. Using multispectrum colorimetric and transmittance optic systems, this instrument detects changes in organism growth under various media and antibiotic concentrations. The device’s analysis algorithm then interprets such readings to provide translation into microorganism identification and susceptibility results. The Vitek 2 Compact also features an advanced expert system that provides fingerprint recognition of bacterial resistance mechanisms and phenotypes. This feature interprets the antibiotic resistance patterns, validates the results, and reports the resistance phenotype.
Bio-Rad Laboratories Inc. (Hercules, CA) obtained FDA marketing clearance for its BioPlex 2200 system, an immunoassay platform that employs multiplexing technology to analyze for multiple disease states from a single patient sample. This instrument is the first clinical diagnostics platform to offer multiplexing technology on a fully automated, fully integrated random-access platform. The BioPlex 2200 system will initially include a panel of assays targeting autoimmune diagnostics. Future assays in development are in the areas of serology, infectious diseases, cardiology, and toxicology.
Dade Behring (Deerfield, IL) received 510(k) clearance for its Dimension Vista 1500 integrated system, the company’s first integrated chemistry/immunochemistry system that is geared for high-volume clinical laboratories. This instrument will combine photometry, turbidimetry, nephelometry, and integrated multisensor technologies. The device’s design integrates analysis of electrolytes and plasma proteins, general and special chemistries, testing for drugs of abuse, therapeutic drugs, and immunosuppressive drugs, cardiac marker tests, and high-sensitivity immunoassays into one analyzer. The Dimension Vista system is being targeted for commercialization during the second half of 2006.
Hitachi Chemical Diagnostics Inc. (Mountain View, CA) introduced its AP 1800 automated in vitro allergy diagnostic system, which tests for circulating allergen-specific IgE antibodies in human serum. The benchtop system automates many tasks, allowing samples to be processed with minimum operator intervention. The device’s multitasking software enables clinical laboratory staff to review results, input further test requests, and evaluate quality control data while the instrument continues to function. The AP 1800 is also designed to minimize the time spent in the pre- and postanalytical phases of testing.
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| Nova Biomedical: The Stat Profile pHOx respiratory analyzer incorporates a seven-test menu including pH, PO2, PCO2, SO2, hemoglobin, nematocrit, and lactate to provide a comprehensive diagnostic picture of oxygen transport. |
Nova Biomedical (Waltham, MA) launched its Stat Profile pHOx respiratory analyzer, which incorporates a seven-test menu including pH, PO2, PCO2, SO2, hemoglobin, hematocrit, and lactate to provide a comprehensive diagnostic picture of oxygen transport. This analyzer uses a liquid-only calibration system that eliminates compressed tanks, gas regulators, gas tubing lines, and humidifiers. In addition, a fully automated quality control system is contained within a single onboard autocartridge quality control pack.
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| Ortho-Clinical Diagnostics: The Vitros 350 chemistry system features a flat-panel, touch-sensitive monitor with an adjustable support arm, and other new capabilities such as higher throughput and faster time to first result. |
Ortho-Clinical Diagnostics (Raritan, NJ) released its Vitros 350 chemistry system, which features a touch-sensitive, flat-panel monitor with an adjustable support arm. This instrument’s other new capabilities include higher throughput and faster time to first result.
Roche Diagnostics (Indianapolis) introduced its Urisys 1800 analyzer, a compact urinalysis instrument for midsized laboratories. Featuring automatic strip detection to decrease operator error and a standard bar code reader for complete patient identification, this device allows operators to customize interface options, operations, and reports.
Stanbio Laboratory (Boerne, TX) received 510(k) clearance for its Sirrus system, a fully automated benchtop chemistry analyzer. This instrument incorporates three features to eliminate the risk of cross-contamination. First, its mixing system uses only air pressure to mix the reagent and sample mixture, thereby avoiding contamination issues that arise from using mechanical stirring devices. Second, its washing system uses a 10-step process to clean the semipermanent cuvettes between test samples. Third, the Sirrus system uses a dual-reagent probe and a separate sample probe to provide carryover-free results.
Data and Information Management
IVD manufacturers have continued to allocate more resources into developing their information management products as a vital part of their business. Interest in information management among companies demonstrates their recognition of the importance of this area to large customers, whose challenges in collecting, analyzing, storing, and transferring data have continually become more sophisticated and complicated. A number of companies have introduced new systems this past year that are designed to streamline information management for their hospital and laboratory customers.
Abbott Laboratories introduced two new laboratory software solutions: Accelerator Decision Manager and an enhanced version of AbbottLink. Accelerator Decision Manager connects a laboratory’s existing information systems to diagnostic instruments, optimizing sample processing and assessment. This program enables the laboratory to automate processes such as result verification, sample location, and quality control analysis. Advanced decision rules can be programmed to route samples and evaluate results based on factors such as patient age, past test results, prescribing physician, hospital ward, and other parameters. Accelerator also works across multiple instruments and diagnostic equipment, offering a scalable program for small to large laboratories.
AbbottLink monitors critical instrument operations and produces management reports that can be used to reduce costs and maximize instrument performance. This software reviews and captures instrument data in real time. AbbottLink allows Abbott service representatives to remotely view instrument operational data, providing quicker resolution of technical issues. With full access to instrument data, logs, files, maintenance records, calibrations, and other performance metrics, laboratories can also monitor their operations, analyzing inventory and other laboratory costs.
Beckman Coulter released DL2000 version 6.4, an update to its data management software that improves laboratory work flow and patient test result management. This program operates in conjunction with a laboratory information system, enabling clinical labs to consolidate test information from various instrument systems and manage the data in real time. With DL2000, operators can control multiple lab processes, from sample-tube identification to test result validation.
To improve patient safety and lab efficiency, DL2000 reduces manual review of test results by performing autovalidation based on user-defined criteria. The system alerts the operator when abnormal, critical, or unexpected results are generated. Reflex testing and delta checking can be performed automatically, based on single or multiple test results. DL2000 can perform automatic sample rerun, and its automatic stat notification eliminates processing delays and speeds delivery of critical sample results to clinicians.
Ortho-Clinical Diagnostics launched the expansion of the testing capabilities of its Vitros 5,1 FS chemistry system through the addition of its user-defined assay software. This program allows laboratories to expand their test menu by developing their own test-method applications to complement the assays currently available on the Vitros 5,1. This software feature enhances the onboard testing capabilities and provides better work flow and workstation consolidation.
The user-defined assay software allows laboratories to program assay protocols using preformatted templates and to define their own protocols. The software supports enzymatic, colorimetric, and turbidimetric assay methodologies on serum, plasma, urine, cerebrospinal fluid, and whole blood hemolysate samples.
Point-of-Care Devices
As one of the fastest-growing market segments in the IVD industry, point-of-care testing continues to mature with new technological advances and wider usage. Broader platforms that integrate protein markers with infectious-disease testing, immunoassays, clinical chemistry, and hematology testing are being pursued as IVD manufacturers continue to observe a movement of testing from centralized laboratories to the patient’s bedside. Manufacturers are recognizing the importance of point-of-care testing in the overall process of patient care, as well as its ability to strengthen a company’s portfolio of testing systems and revenue streams. The increase of activity in the point-of-care testing market has also prompted many IVD manufacturers to rethink their distribution strategies. In many cases, manufacturers have formed dedicated sales teams to supplement or replace contracted sales agreements.
Abaxis Inc. (Union City, CA) introduced its Piccolo Lipid Panel Plus, which diagnoses patients for heart disease and metabolic syndrome, and performs liver enzyme monitoring—combined in one point-of-care test. With the addition of alanine aminotransferase, aspartate aminotransferase, and glucose, this lipid panel can provide the first simultaneous screening and monitoring tool for the management of patients’ cardiac health and treatment outcomes. The lipid panel meets the performance criteria set by the Centers for Disease Control and Prevention’s Cholesterol Reference Method Laboratory Network.
Abbott Diabetes Care (Alameda, CA) received 510(k) clearance to market its FreeStyle Connect blood glucose– monitoring system in the point-of-care setting. The technology employed by this glucose monitor ensures reliable results under real-world conditions, with accuracy independent of blood oxygen levels. Results are not affected by common substances such as aspirin, acetaminophen, gentisic acid, uric acid, vitamins, and many over-the-counter drugs. FreeStyle Connect is also designed to interface seamlessly with any open point-of-care data management system.
FreeStyle Connect uses a technology based on coulometric measurement that is exclusive to all FreeStyle meters. This electrochemical technology measures virtually all of the available glucose in a blood sample, making it ideal for measuring a small sample size.
American Bio Medica Corp. (Kinderhook, NY) obtained 510(k) clearance for its Rapid TEC4 point-of-collection drug screen. This clearance is the third one that the company has received related to its Rapid TEC product line. The Rapid TEC products each contain one individual drug-testing strip that includes the chemistry to detect more than one class of drug. These three clearances allow American Bio Medica to provide various configurations of 2–14 classes of drugs of abuse.
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| Biosite: The Triage MeterPlus runs the Triage D-Dimer test, a point-of-care test that aids in the assessment and evaluation of patients suspected of having thromboembolic events, including pulmonary embolism and deep vein thrombosis. |
Biosite Inc. (San Diego) launched its Triage D-Dimer test, which aids in the assessment and evaluation of patients suspected of having thromboembolic events, including pulmonary embolism and deep vein thrombosis. This point-of-care diagnostic test provides D-dimer results in approximately 15 minutes and can be used in the emergency department or at a patient’s bedside. The test uses highly sensitive immunoassay technology and the highly specific dB6 D-dimer antibody. The Triage D-Dimer test is run on the Triage MeterPlus and correlates with other enzyme-linked immunosorbent assay–based D-dimer tests.
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| HemoCue: The Urine Albumin system, a point-of-care device for the qualitative determination of microalbuminuria, consists of a portable analyzer and disposable cuvettes that contain freeze-dried reagents with anti-human-albumin antibodies. |
HemoCue (Lake Forest, CA) released its Urine Albumin system, a point-of-care device for the qualitative determination of microalbuminuria. The system consists of a portable analyzer and disposable cuvettes that contain freeze-dried reagents with anti-human-albumin antibodies. The sample is drawn into the cuvette by capillary action, placed in the analyzer, and mixed through vibration. The measuring range is 10–150 mg/L, and the analyzer requires 15 microliters of a spot or timed urine collection.
Roche Diagnostics received FDA clearance for a new test on its Omni blood gas analyzer, which measures pH in pleural fluid samples. The Omni blood gas analyzers provide point-of-care settings with additional time-saving features including a fully automated quality control system, zero-maintenance electrodes, and liquid calibration, which eliminates the need for gas tanks.
Immunoassays
According to a report by Kalorama Information (New York City), worldwide sales of immunoassays totaled $4.9 billion in 2003, and are projected to grow by 9% annually to reach $7.5 billion by 2008. Immunoassay developers are on a continuous hunt to discover technologies that can detect nano- and picoconcentrations of proteins and pathogens in clinical samples. Such ultrasensitive test methodologies allow researchers to discover specific markers for diseases such as diabetes, cancer, osteoporosis, arthritic conditions, and cardiac disease.
With such ongoing research efforts, immunoassays will exhibit higher performance levels in the future. Several assays that were released this past year demonstrated increased sensitivities and specificities, with future assays promising measurements to pico levels of an analyte. High-performance immunoassays provide increased diagnostic capabilities, thereby opening the door for lifelong management of various pathologies. For example, in the cardiac vascular area, the term high sensitivity has evolved and found its way into product labeling. Risk stratification for cardiac patients has become a reality rather than a paradox through immunoassay improvement.
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| Abbott Laboratories: The Architect Stat myoglobin test completes the acute cardiac menu for the Architect systems, which also includes tests for troponin-I and creatine kinase-MB. |
Abbott Laboratories introduced four prostate cancer tests for its Architect family of analyzers and its AxSym automated immunoassay instrument system. Those tests are the Architect Free PSA, the Architect Total PSA, the AxSym Free PSA, and the AxSym Total PSA. The Total PSA tests are equimolar immunoassays that assess the overall amount of prostate specific antigen (PSA) in the blood and equally measure concentrations of free PSA and complexed PSA. The Free PSA tests identify a form of PSA that is not bound to other proteins and are used in conjunction with the Total PSA assays to calculate the percentage of free PSA in the blood.
Earlier this year, Abbott Laboratories received 510(k) clearance for a myoglobin test for use on its Architect i2000SR immunoassay system and Architect ci8200 immunochemistry system. The Architect Stat myoglobin test completes the acute cardiac menu for the Architect system, which also includes tests for troponin-I and creatine kinase-MB.
Abbott Laboratories also announced that its manufacturing partner, Axis-Shield (Dundee, Scotland), received 510(k) clearance from FDA for an automated sirolimus test for monitoring the therapeutic levels of antirejection drug Rapamune by Wyeth Pharmaceuticals (Madison, NJ) in whole blood. The IMx Sirolimus assay utilizes Abbott’s IMx system and uses microparticle enzyme immunoassay technology to measure and qualify the amount of sirolimus in a patient’s blood sample.
American Diagnostica Inc. (Stamford, CT) launched its Acticlot dPT, a dilute prothrombin time test kit that includes a formulated, high-phospholipid reagent for confirming a positive dPT lupus anticoagulant screening test. This test identifies lupus anticoagulants that affect coagulation initiated by tissue factor–mediated activation of the extrinsic pathway. The test can be run simultaneously on most automated analyzers along with other lupus anticoagulant tests.
Bayer Diagnostics released its sixth FDA-approved, automated assay for hepatitis on its Advia Centaur immunoassay system. FDA approved Bayer’s Hepatitis A (HAV) Total assay for the qualitative determination of total antibodies to the hepatitis A virus in human serum or plasma. Laboratories can use this assay to aid in diagnosing previous or ongoing hepatitis A viral infection, or identifying HAV-susceptible individuals for vaccination. With this approval, Bayer offers a comprehensive test panel for hepatitis testing, including two assays for the hepatitis A virus (HAV IgM and Total), three assays for the hepatitis B virus (HBc IgM, anti-HBs, and HBc Total), and an assay for the hepatitis C virus (anti-HCV).
By offering the HAV Total assay on the Advia Centaur system, Bayer Diagnostics has made the hepatitis panel ideal for medium- and large-volume laboratories. The addition of this assay to the platform allows laboratorians to enhance their level of automation in performing these assays with such features as software that provides automatic algorithm processing, cascade reflex testing, user-defined panels, automatic repeats of critical samples, and sample and reagent integrity checks.
Bayer Diagnostics also introduced a menu expansion for its Advia 1650 and 2400 analyzers. Nine new tests for drugs of abuse (e.g., cannabinoid, opiate, benzodiazepine, methadone, phencyclidine, propoxyphene, cocaine, amphetamine, and barbiturate) are available on these analyzers, offering laboratory professionals the ability to perform initial patient screening for the use of illegal drugs.
Beckman Coulter received 510(k) clearance for a benzodiazepine assay. Available on the company’s Synchron-series chemistry analyzers, the test provides a rapid screening procedure for determining the concentration of benzodiazepine in human urine at a cutoff value of 200 ng/ml oxazepam. This assay features increased sensitivity to benzodiazepine-glucuronide metabolites in urine with the addition of ß-glucuronidase enzyme. This enzyme helps to remove glucuronides that commonly interfere with the detection of antidepressant drugs. The prefilled, bar coded cartridges simplify handling and allow laboratory technologists to track usage, stability calibration frequency, and lot numbers. Meanwhile, the qualitative, interpretive report delivers a positive or negative result, which eliminates the need for manual manipulation.
In an effort to bolster the anemia menu on its Access immunoassay system family, Beckman Coulter launched a reformulated test for folate to aid in the diagnosis of conditions that are related to folate-deficiency anemia. As part of the reformulation, the kit provides a single calibration for both serum or plasma folate and red blood cell folate applications. The test can be performed on whole blood, serum, or heparinized plasma, and features automated pretreatment of serum or hemolysate samples.
Beckman Coulter also released a reformulated phosphorus assay with minimal response to paraprotein interferences. This assay enables commercial laboratories and hospitals to determine quantitatively the concentration of phosphorus in serum, plasma, or urine. Available on the company’s UniCel DxC and Synchron family of chemistry systems, the phosphorus test includes automatic on-line urine sample dilution at a 1:10 ratio, which eliminates the need for off-line sample-preparation steps.
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| Bio-Rad Laboratories: The Multispot HIV-1/HIV-2 rapid test, which aids in diagnosing HIV-1 and HIV-2, is a single-use qualitative enzyme immunoassay that can be used on both fresh and frozen serum and plasma samples. |
Bio-Rad Laboratories received FDA approval for its Multispot HIV-1/HIV-2 rapid test, which aids in diagnosing HIV-1 and HIV-2. This single-use qualitative enzyme immunoassay can be used on both fresh and frozen serum and plasma samples. Clinical studies on a large number of HIV-1 and HIV-2 antibody positive and negative samples have shown that the test provides a high level of sensitivity and specificity. The assay is also suitable for use in multitest algorithms that are designed for statistical validation of rapid HIV test results. The test is moderately complex and approved for use in CLIA-certified laboratories.
Biosite released its Triage Stroke panel in Europe, which is a rapid immunoassay intended to be used for assessing and diagnosing cerebral ischemia, or stroke. This test uses a small sample of blood to measure simultaneously four biomarkers: brain natriuretic peptide (BNP), D-dimer, MMP-9, and S100ß. The assay is the first commercialized Biosite test to incorporate the company’s MultiMarker Index feature, which analyzes information from multiple biomarkers and presents a single composite index result. While the test is currently not approved for sale in the United States, FDA accepted the Triage Stroke panel’s premarket approval application for further review.
Biosite has also been developing a second-generation Triage Cardio Profiler panel that will include myeloperoxidase (MPO). The company believes that the addition of MPO can advance the diagnostic utility of the product, which is used for emergency assessment of chest-pain patients. The panel currently measures the levels of troponin I, CK-MD, BNP, and myoglobin in blood. It is also used as an aid in the diagnosis of myocardial infarction, diagnosis and assessment of the severity of congestive heart failure, and risk stratification of patients with acute coronary syndromes. Biosite has targeted commencing clinical trials for the Triage Cardio Profiler panel with MPO during the third quarter of 2005. Pending the completion of clinical trials for the product, the company anticipates filing a 510(k) premarket notification with FDA by the fourth quarter of 2005.
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| Dade Behring: The Emit II Plus Ecstasy assay is a rapid screening method for detecting the presence of Ecstasy in urine and has approved applications for use on various systems. |
Dade Behring received 510(k) clearance from FDA for its Emit II Plus Ecstasy assay, a rapid screening method for detecting the presence of Ecstasy in urine. This assay complies with proposed Substance Abuse and Mental Health Services Administration (SAMHSA) regulations, and has approved applications for use on various systems by Olympus Diagnostics (Melville, NY) and Dade’s Syva 30R analyzer. The assay also meets laboratory demand for an Ecstasy-specific test that includes a 500-ng/ml cutoff level to satisfy the proposed SAMHSA drug-testing guidelines. It is intended to be used as a stand-alone test or in conjunction with the Emit II Plus amphetamines assay, which detects Ecstasy at higher levels.
Dade Behring also obtained FDA clearance for its NT-proBNP test for use on its Stratus CS Acute Care diagnostics system. This assay has been cleared to aid in diagnosing heart failure, including the assessment of heart failure severity in patients diagnosed with congestive heart failure, and risk stratification of patients with acute coronary syndrome and heart failure. Last December, the company received FDA clearance for the use of the NT-proBNP test on its Dimension instruments with heterogeneous immunoassay modules.
In addition, Dade Behring received FDA clearance for the use of its Advanced D-Dimer assay as an aid in diagnosing venous thromboembolism. The clearance included performance data with a defined cutoff value for the Dade Behring BCS system and Sysmex CA-1500 system. The assay is also used on Dade Behring’s BCT system, and Sysmex CA-7000 and CA-560 systems.
Diagnostic Chemicals Ltd. (Oxford, CT) announced that its enzymatic, liquid-stable Acetaminophen-SL assay received 510(k) clearance for the quantitative determination of the drug in human plasma. Optimized for use on a variety of different instrument platforms, this assay is suited for use with fully automated testing procedures, with an extensive listing of available applications.
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| Fujirebio Diagnostics: The Mesomark assay, the first blood test for mesothelioma is a manual enzyme-linked immunosorbent assay (ELISA) that identifies serum tumor markers called soluble mesothelin-related peptides. |
Fujirebio Diagnostics Inc. (Malvern, PA) submitted a 510(k) application in April for its Mesomark assay, the first blood test for mesothelioma. This manual enzyme-linked immunosorbent assay (ELISA) works by identifying serum tumor markers called soluble mesothelin-related peptides. The company’s mesothelioma assay is a two-step immunoassay that quantitates these peptides in human blood using a standard ELISA microplate sandwich assay format. While the Mesomark test has not yet received FDA clearance and is still undergoing review, it is being marketed in Europe and Australia.
Olympus Diagnostics received FDA clearance for its C-reactive protein (CRP) latex assay as an independent cardiac risk marker. This assay offers three applications covering a variety of measuring ranges to quantify CRP in human serum. The assay is designed for use on the full line of Olympus chemistry-immuno analyzers.
Ortho-Clinical Diagnostics received 510(k) clearance for its direct High Density Lipoprotein (dHDL) slide. This assay will be available on most automated Vitros chemistry systems and will be used to quantitatively measure high-density lipoprotein cholesterol concentration in serum and plasma. The dHDL slide offers the advantages of a rapid, automated, random-access test, and does not require sample pretreatment. The test is performed in a single step versus traditional dHDL assays that require multiple steps. Interferents such as triglycerides, LDL, hemoglobin, total protein, and a number of commonly prescribed medications do not affect the test’s performance.
Ortho-Clinical Diagnostics also introduced 20 MicroTip assays on its Vitros 5,1 FS chemistry system. With this expanded menu, therapeutic drug monitoring assays and serum proteins can be performed together with general chemistry tests on a single system, eliminating the need to batch or split samples. These assays use a technology that allows them to be processed using disposable tips and cuvettes. This technology eliminates the maintenance and cost associated with water, wash reagents, plumbing, drains, fixed probes, and mixing assemblies. The technology also eliminates sample and reagent carryover that may occur with sample probes, uncapped reagents, and reusable cuvettes. Among the new MicroTip assays, the Vitros caffeine assay has FDA clearance for assessing neonatal apnea. In addition, the high-sensitivity C-reactive protein assay is cleared for assessing the risk of developing coronary heart disease. It runs on a random-access chemistry system.
Roche Diagnostics received FDA clearance for its Elecsys PreciControl tumor marker control solution. This tumor marker provides laboratory professionals with the same control for six different tumor marker tests. The company also received clearance for its Elecsys CA 19-9 assay. In addition, Roche has other tumor markers that are currently in development.
Molecular Diagnostics
Promising better sensitivity and specificity, molecular diagnostic technologies have been developing rapidly with assay menus that have grown significantly. Nucleic acid testing is being applied to practically all areas of biological sample testing, including genotyping, infectious-disease diagnostics, cancer and cardiac marker testing, and industrial and environmental tests. This trend has resulted in assay menus that, unlike immunoassays, consist of large numbers of low- to medium-volume tests, in addition to the usual high-volume tests.
However, despite the potential of molecular diagnostics, the technology has proven difficult to integrate into laboratories and hospitals. Due to the sensitivity of amplification and the risk of cross-contamination, nucleic acid testing is currently limited to being performed by highly trained technologists in highly controlled facilities.
The problem of labor, combined with the market demand, has highlighted the need for automated systems that are appropriately designed for low-volume testing but still have a large assay menu. IVD manufacturers have introduced such products that are aimed at answering the market need at hospitals and near-patient sites, while developing high-throughput automated systems for centralized labs.
Affymetrix Inc. (Santa Clara, CA) received FDA clearance for its GeneChip System 3000Dx, an instrumentation system for analyzing IVD microarrays. This system is the first microarray instrument to be cleared by FDA for IVD use, providing a standardized platform for nucleic acid diagnostics. FDA’s clearance of the 3000Dx system represents a major step toward the use of microarrays for clinical applications.
Applied Imaging Corp. (San Jose, CA) received 510(k) clearance to market its Ariol Her-2/neu fluorescence in situ hybridization (FISH) application, which is designed to detect Her-2/neu gene amplification in breast cancer biopsy samples via FISH. The application complements and completes the breast cancer panel on the company’s Ariol system. The Ariol Her-2/neu FISH application assists in analyzing a complex test that is an important factor in evaluating and selecting certain breast cancer patients for the drug Herceptin from Genentech Inc. (South San Francisco, CA).
Beckman Coulter introduced its Vidiera NsP nucleic sample preparation platform for automated extraction and downstream reaction setup. Based on the company’s primary tube handling and Biomek automation technologies, this platform can replace several instruments and enable labs to centralize preanalytical functions. Through an agreement with Qiagen (Venlo, The Netherlands), Beckman will offer custom extraction reagents for purifying viral nucleic acids from serum and plasma samples, and genomic DNA from blood samples. Beckman has validated these chemistries, along with specific labware, for use on the Vidiera NsP. The platform and reagents are ideal for virology and pathology applications and can be integrated with Beckman Coulter’s Vidiera NsD nucleic sample detection system.
bioMérieux launched its NucliSens easyMAG system, an automated sample-preparation platform for extracting nucleic acids in molecular diagnostic assays. This platform is based on the nucleic acid–binding property of silica. By using magnetic silica particles for enhanced automation and by further optimizing the extraction reagents, a high quality of extracts can be obtained from a wide variety of sample types. This system offers high-throughput automated nucleic acid extraction with minimum hands-on time.
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| Gen-Probe: The Aptima GC assay, an amplified nucleic acid test, detects on a stand-alone basis the bacterium that causes gonorrhea and was cleared to detect gonorrhea from a wide variety of sample types. |
Gen-Probe Inc. (San Diego) received FDA marketing clearance for its Aptima GC assay, an amplified nucleic acid test that detects on a stand-alone basis the bacterium that causes gonorrhea. This assay was cleared to detect gonorrhea from a wide variety of sample types, including clinician-collected endocervical, vaginal, and urethral swab specimens, patient-collected vaginal swab specimens, and female and male urine specimens. The assay can be run on Gen-Probe’s semiautomated DTS instruments. Last December, the company received clearance to market its stand-alone Aptima CT assay for detecting chlamydia.
IQuum Inc. (Allston, MA) released its Liat FlowCycler, a multisample nucleic acid test system. This device uses flow cycling to avoid thermal block ramping that is used in traditional polymerase chain reaction (PCR) thermal cyclers, to allow the system to achieve rapid reactions without sacrificing efficiency or reaction volume. The FlowCycler has two separate bays that can concurrently perform two separate reactions, allowing the system to be used as two independent PCR thermal cyclers. The instrument also provides integrated four-channel fluorescence detection for each tube, allowing quantitative and qualitative analysis of multiple targets in real time.
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| Nanogen: The NanoChip 400 is an automated multipurpose system that facilitates the detection of known genetic sequences and utilizes a 400-site electronic microarray upon which molecular tests can be developed and conducted. |
Nanogen Inc. (San Diego) introduced its NanoChip 400, an automated multipurpose system that facilitates the detection of known genetic sequences, such as single nucleotide polymorphisms (SNPs). This system utilizes a 400-site electronic microarray upon which molecular tests can be developed and conducted. Based on technology that combines microelectronics and biology, electrical potential is controlled at each of the 400 test sites to move and concentrate DNA or RNA. The chip’s open-architecture design permits users to define, select, and build their own test panels, or select from Nanogen’s predefined analyte specific reagents (ASRs).
Roche Diagnostics announced that FDA cleared its AmpliChip CYP450 test for diagnostic use. This test analyzes a patient’s cytochrome P450 2D6 and 2C19 genotypes from genomic DNA that is extracted from blood samples. Test results allow physicians to consider unique genetic information from patients in selecting medications and doses of medications for a wide variety of common conditions such as cardiac diseases, pain, and cancer. The test combines the strengths of Roche’s PCR amplification technology and Affymetrix’s high-density microarray technology.
Third Wave Technologies Inc. (Madison, WI) announced that FDA approved its Invader UGT1A1 molecular assay for IVD use. This assay is the first pharmacogenetic test to be approved by FDA for use as a companion diagnostic to a specific drug therapy. The Invader test is intended to identify patients who may be at increased risk of adverse reactions to the chemotherapy drug Camptosar. The assay detects specific mutations in the UGT1A1 gene that have been associated with such risk.
Tm Bioscience Corp. (Toronto) announced that FDA cleared its Tag-It Cystic Fibrosis kit, the first multiplexed genotyping test for detecting cystic fibrosis. This test identifies a group of variations in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR) that causes cystic fibrosis. FDA approved the test based on the company’s study of hundreds of DNA samples, which showed that the test identifies the CFTR gene variations with a high degree of certainty.
Conclusion
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| Hitachi Chemical Diagnostics: The AP 1800 automated in vitro allergy diagnostic system tests for circulating allergen-specific IgE antibodies in human serum and automates many tasks allowing samples to be processed with minimum operator intervention. |
With new molecular products on the market, an increased demand for instruments with greater automation and connectivity, and ever increasing opportunities for bringing point-of-care tests for a variety of samples to market, it has been a prosperous year for IVD manufacturers. Partnerships with pharmaceutical companies have planted the seeds for the future of personalized medicine.
In addition to smaller, less expensive, faster, and more-accurate traditional IVDs, IVD manufacturers have been developing new tests that are tied intimately to pharmaceuticals. More and more of these personalized-medicine IVDs will likely be introduced into the marketplace in upcoming years.
Moreover, future advances in IVDs will bring diagnostic testing even closer to the patient, and provide more-accurate, faster, and simpler testing to the marketplace. As IVD manufacturers deliver on the promise of ever better diagnostics, IVD Technology will be here to take note of their progress.
Richard Park is editor of IVD Technology.
Copyright ©2005 IVD Technology
