Who is the manufacturer of Dimension Vista High-Sensitivity Troponin I (TNIH) Assay?

Siemens Healthcare Diagnostics, Inc. filed the 510(k) submission for Dimension Vista High-Sensitivity Troponin I (TNIH) Assay (K182225).

What is the FDA product code for Dimension Vista High-Sensitivity Troponin I (TNIH) Assay?

MMI. It is classified under 21 CFR 862.1215 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for Dimension Vista High-Sensitivity Troponin I (TNIH) Assay?

510(k) clearance (submission type: Traditional).

Who can help prepare an FDA 510(k) submission like Dimension Vista High-Sensitivity Troponin I (TNIH) Assay?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

Dimension Vista High-Sensitivity Troponin I (TNIH) Assay

Q: What are the predicate devices for Dimension Vista High-Sensitivity Troponin I (TNIH) Assay?

Elecsys Troponin T Gen 5 STAT (K162895).

K182225 · Siemens Healthcare Diagnostics, Inc. · MMI · Mar 4, 2019 · Clinical Chemistry

Device Facts

Record ID	K182225
Device Name	Dimension Vista High-Sensitivity Troponin I (TNIH) Assay
Applicant	Siemens Healthcare Diagnostics, Inc.
Product Code	MMI · Clinical Chemistry
Decision Date	Mar 4, 2019
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.1215
Device Class	Class 2

Intended Use

The Dimension Vista High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human plasma using the Dimension Vista® system. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).

Device Story

The Dimension Vista TNIH assay is a homogeneous, sandwich chemiluminescent immunoassay using LOCI technology. It processes lithium heparin plasma samples on the Dimension Vista system. The assay utilizes two synthetic bead reagents (Sensibeads coated with streptavidin/photosensitizer dye; Chemibeads coated with anti-cardiac troponin I monoclonal antibody/chemiluminescent dye) and biotinylated anti-cardiac troponin I monoclonal antibody fragments. Sample incubation forms bead-cardiac troponin I-biotinylated antibody sandwiches; addition of Sensibeads creates bead-pair immunocomplexes. Illumination at 680 nm triggers singlet oxygen diffusion from Sensibeads to Chemibeads, inducing chemiluminescence measured at 612 nm. The signal intensity is directly proportional to cardiac troponin I concentration. Used in clinical laboratories, the assay provides quantitative results to clinicians to assist in diagnosing AMI. The device benefits patients by enabling rapid, sensitive detection of cardiac troponin I, facilitating timely clinical decision-making for suspected myocardial infarction.

Clinical Evidence

Prospective study of ~2500 subjects presenting with ACS symptoms at 29 U.S. emergency departments. Diagnoses adjudicated by cardiologists/emergency physicians per Third Universal Definition of Myocardial Infarction. AMI prevalence was 13.0%. Clinical performance (sensitivity, specificity, PPV, NPV) was evaluated across serial time intervals from presentation. Pooled sensitivity ranged from 79.0% (0-<1.5h) to 94.2% (4.5-<6h), with NPVs consistently >96%.

Technological Characteristics

Homogeneous sandwich chemiluminescent immunoassay using LOCI technology. Reagents: two synthetic bead reagents (Sensibeads, Chemibeads) and biotinylated anti-cardiac troponin I monoclonal antibody fragments. Energy source: 680 nm illumination. Measuring interval: 3.0 – 25,000.0 pg/mL. Sample type: lithium heparin plasma. Connectivity: integrated with Dimension Vista system. Calibration stability: 30 days. Open well stability: 7 days.

Indications for Use

Indicated for use in patients presenting with symptoms consistent with acute coronary syndrome (ACS) to aid in the diagnosis of acute myocardial infarction (AMI).

Regulatory Classification

Identification

A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Predicate Devices

Elecsys Troponin T Gen 5 STAT (K162895)

Related Devices

K190675 — Dimension EXL High-Sensitivity Troponin I (TNIH) Assay · Siemens Healthcare Diagnostics, Inc. · May 17, 2019
K053577 — DIMENSION VISTA CTNI FLEX FLEX REAGENT CARTRIDGE, CALIBRATOR AND SDIL SAMPLE DILUENT · Dade Behring, Inc. · Apr 14, 2006
K063756 — DIMENSION VISTA CTNI FLEX REAGENT CARTRIDGE · Dade Behring, Inc. · Mar 19, 2007
K081643 — DIMENSION TNI FLEX REAGENT CARTRIDGE, AND CTNI SAMPLE DILUENT WITH MODELS, RF621, KD692 · Siemens Healthcare Diagnostics · Jul 3, 2008
K202525 — Alinity i STAT High Sensitivity Troponin-I · Abbott Laboratories Diagnostics Division · May 19, 2022

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue. March 4, 2019 Siemens Healthcare Diagnostics, Inc. Laura Duggan Sr. Mgr. Regulatory Affairs 500 GBC Drive. M/S 514 Newark, DE 19714 Re: K182225 Trade/Device Name: Dimension Vista High-Sensitivity Troponin I (TNIH) Assay Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: January 24, 2019 Received: January 25, 2019 Dear Laura Duggan: We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part {1}------------------------------------------------ 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm. For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely, # Kellie B. Kelm -S for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ ## Indications for Use 510(k) Number (if known) k182225 Device Name Dimension Vista High-Sensitivity Troponin I (TNIH) assay Indications for Use (Describe) The Dimension Vista® High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human plasma using the Dimension Vista system. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI). | Type of Use (Select one or both, as applicable) | |-------------------------------------------------| |-------------------------------------------------| | X Prescription Use (Part 21 CFR 801 Subpart D) | |--------------------------------------------------------------------------------------------------------| | Over-The-Counter Use (21 CFR 801 Subpart C) | #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ # SECTION 7: 510(K) SUMMARY This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92. ## ASSIGNED 510(K) NUMBER The assigned 510(k) number is k182225. ## APPLICANT AND DATE Laura J. Duggan, Ph. D., RAC Siemens Healthcare Diagnostics Inc. 500 GBC Drive, M/S 514 Newark, DE 19714-6101 Email: laura.j.duggan@siemens-healthineers.com Phone: 302-631-7654 Fax: 302-631-0493 January 24, 2018 ## MANUFACTURER Siemens Healthcare Diagnostics Inc. 500 GBC Drive Newark, DE 19714-6101 Registration Number: 2517506 #### REGULATORY INFORMATION Regulatory Submission for the Dimension Vista High-Sensitivity Troponin I (TNIH) Assay | Device: | Immunoassay method, troponin subunit | |-------------------------|------------------------------------------------------------------| | Regulation Description: | Creatine phosphokinase/creatine kinase or isoenzymes test system | | Proprietary Name: | Dimension Vista High-Sensitivity Troponin I (TNIH) Assay | | Regulation Number: | 21CFR862.1215 | | Classification: | Class II | {4}------------------------------------------------ | Product Code: | MMI | |-------------------|--------------------------------------------| | Panel: | Clinical Chemistry | | Predicate Device: | Elecsys Troponin T Gen 5 STAT (K162895) | ## DEVICE DESCRIPTION ## DIMENSION VISTA HIGH-SENSITIVITY TROPONIN I (TNIH) ASSAY The Dimension Vista® TNIH assay is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI® technology. The LOCI reagents include two synthetic bead reagents and two biotinylated anti-cardiac troponin I monoclonal antibody fragments. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with a third anticardiac troponin I monoclonal antibody and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibodies to form bead-cardiac troponin Ibiotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the cardiac troponin I concentration in the sample Lithium heparin plasma specimens may be used. The reagent is stored unopened at 2 – 8 °C, is stable sealed on system for 30 days and opened on the system for 7 days. Calibration is performed every 30 days for a reagent lot. ## INTENDED USE/INDICATIONS FOR USE #### DIMENSION VISTA HIGH-SENSITIVITY TROPONIN I (TNIH) ASSAY The Dimension Vista High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human plasma using the Dimension Vista® system. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI). ## SUBSTANTIAL EQUIVALENCE COMPARISON Below is a substantial equivalence comparison for the Dimension Vista High-Sensitivity Troponin I (TNIH) Assay vs. the Elecsys Troponin T Gen 5 STAT (K162895) device. {5}------------------------------------------------ | Feature | Predicate Device: Elecsys Troponin T Gen 5 STAT (K162895) | New Device: DIMENSION VISTA HIGH- SENSITIVITY TROPONIN I (TNIH) ASSAY | |-----------------------------------|--------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use : | Immunoassay for the in vitro quantitative determination of cardiac troponin T (cTnT) in lithium heparin plasma. | The High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human plasma using the Dimension Vista® system. | | Indications for Use: | The immunoassay is intended to aid in the diagnosis of myocardial infarction. | The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI). | | Device Technology: | Electrochemiluminescence immunoassay | Homogeneous immunoassay | | Sample Type: | Lithium Heparin Plasma | Lithium Heparin plasma | | Expected Values: | 99th percentile were determined to be: • 19 ng/L for both • 14 ng/L for females • 22 ng/L for males | 99th percentile determined for plasma 58.9 pg/mL overall female 53.7 pg/mL plasma male 78.5 pg/mL plasma | | Calibration Frequency: | after 12 weeks when using the same reagent lot | 30 days for any one lot | | Analytical Measuring Interval: | 6-10,000 ng/L | 3.0 – 25,000.0 pg/mL [ng/L] | | Interferences: | No interference in plasma at: Hemoglobin - 100 mg/dL Bilirubin 25 mg/dL Lipemia (Intralipid®) — 1500 mg/dL | No interferences in plasma at approximately 40 pg/mL and approximately 1350 pg/mL of cardiac troponin I from: Hemoglobin - 400 mg/dL Bilirubin (Unconjugated) – 40 mg/dL | | | | Bilirubin (Conjugated) – 30 md/dL Lipemia (Intralipid®) - 3000 mg/dL | | Calibrators: | Elecsys Troponin T Gen 5 STAT calibrators (CalSet Troponin T Gen 5 STAT) | High-Sensitivity Troponin I Calibrator (TNIH Cal), Cat. No. KC627 | {6}------------------------------------------------ ## SUMMARY OF PERFORMANCE TESTING Assay performance results for the Dimension Vista High-Sensitivity Troponin I (TNIH) assay was determined by processing the appropriate body fluids. Summary statistics for each are provided. The following data represent typical assay performance. All data were collected on the Dimension Vista 1500 Analyzer. #### DETECTION LIMIT The Limit of Blank (LoB) and Limit of Detection (LoD) were evaluated in accordance with CLSI EP17-A2 Protocols for Determination of Limits of Detection and Limits of Quantitation: Approved Guideline. Assessment of LoB was the 95th percentile of all values (sorted from lowest to highest), using non-parametric approach. LoB Rank Position = 0.5 +0.95*B, where B=total reps=60; Rank = 57.5 The nonparametric approach described in EP17-A2 was followed to determine the Limit of Detection. LoD was tested separately for lithium heparin specimens. | Dimension Vista High-Sensitivity Troponin I (TNIH) - Limit of Detection Results | | | |---------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------|--------------------| | Limit | Protocol | Result | | LoB | 5 samples with no analyte (calibrator Level 1) were tested (N=4) for 3 days, one run per day, 3 reagent lots | 1.0 pg/mL | | LoD | At least 5 low analyte samples were tested (N=4) for 3 days for native lithium heparin plasma, one run per day, 3 reagent lots | 0.7 - 1.9 pg/mL | Results are consistent with a LoB of 1.0 pg/mL and a LoD of 2.0 pg/mL {7}------------------------------------------------ The Limit of Quantitation (LoQ) for plasma was determined as the analyte level with a within-lab CV of less than or equal to 20.0%. Testing was completed two times a day (n=2) for at least 20 days for a total of 80 replicates with at least 6 native lithium heparin plasma pools on one instrument. LoQ Lot Summary | Reagent Lot | Lot-1 | Lot-2 | Lot-3 | |---------------------------------------|-------|-------|-------| | Lithium Heparin Plasma 20% CV (pg/mL) | 1.2 | 2.4 | 2.2 | The LoQ for Dimension Vista TNIH was determined to be 3.0 pg/mL. For lithium heparin plasma the analyte level with a within-lab CV of less than or equal to 10.0% was determined using CLSI EP5-A3, Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline - Third Edition. Testing was completed two times a day (n=2) for at least 20 days for a total of 80 replicates with at least 6 native lithium heparin plasma pools on one instrument. #### 10% CV Lot Summary | Reagent Lot | Lot-1 | Lot-2 | Lot-3 | |---------------------------------------|-------|-------|-------| | Lithium Heparin Plasma 10% CV (pg/mL) | 2.7 | 5.7 | 5.4 | The 10% CV limit for Dimension Vista TNIH of 10.0 pg/mL is consistent with the data. #### PRECISION STUDIES Precision testing was performed in accordance with CLSI EP05-A3 Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline -Third Edition. Precision was tested n = 2 replicates, two times a day for at least 20 days for a total of 80 replicates with controls and plasma pools on one instrument. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP05-A3. The data are summarized in the following table. All precision goals were met. | | | Repeatability | | Within-Lab | | |----------|------------|---------------|------|------------|-----| | Material | Mean pg/mL | SDa pg/mL | %CVb | SD pg/mL | %CV | | Plasma 1 | 48.9 | 1.12 | 2.3 | 3.05 | 6.2 | | Plasma 2 | 157.7 | 1.55 | 1.0 | 2.60 | 1.6 | | QC | 8088.5 | 99.54 | 1.2 | 200.36 | 2.5 | aSD = standard deviation {8}------------------------------------------------ b CV = coefficient of variation ## LINEARITY STUDY Linearity was evaluated with 16 lithium heparin plasma samples which spanned the assay measuring interval. Each was prepared by mixing high and low concentration samples across the measurement interval as described in CLSI Evaluation of the Linearity of Quantitative Measurement Procedure (EP06-A). The high samples and the low samples for lithium heparin plasma were native. At least five replicates were measured for each sample. The mean of these replicates was used for the calculations. The assay was considered linear across the measuring interval if the p values of nonlinear terms in the quadratic and cubic fit equations are nonsignificant (p ≤ 0.05). If the p-value is > 0.05, then the allowable bias is ≤ 10% or 3 pg/mL, whichever is greater. The testing confirmed linearity from 3.0 - 25,000.0 pg/mL. ## INTERFERENCES CLSI EP7-A2 was followed for the interference testing. The interference study was conducted using a "paired difference scenario" approach where these compounds were spiked into fresh sample pools containing either low or high levels of troponin in lithium heparin troponin I pools. All exogeneous compounds were spiked into the troponin control pools at two levels. Endogeneous compounds were only tested at elevated levels as they are natively found in specimen samples. Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference. Dilution studies were conducted to determine the level at which the spiked substance no longer displayed significant interference. Dilution studies were conducted at two analyte concentrations, if both sample pools show significant interference. | Substance Tested | Substance concentration | Bias (%) | |---------------------------------|----------------------------|----------| | Hemoglobin hemolysate (monomer) | 400 mg/dL [0.25 mmol/L] | <10 | | Bilirubin (conjugated) | 30 mg/dL [356 $\mu$ mol/L] | <10 | | Bilirubin (unconjugated) | 40 mg/dL [684 $\mu$ mol/L] | <10 | | Lipemia (Intralipid®) | 3000 mg/dL [33.9 mmol/L] | <10 | No interference was detected at the following analyte concentrations. | | Low or Therapeutic Concentration | | High or Toxic Concentration | | |---------------------------------------|----------------------------------|--------------|-----------------------------|---------------| | Potential Interferent | Conventional Units | SI Units | Conventional Units | SI Units | | Abciximab | 0.4 mg/dL | NA | 4.0 mg/dL | NA | | Acetaminophen | 2.0 mg/dL | 133 µmol/L | 20.0 mg/dL | 1324 µmol/L | | Acetylsalicylic acid | 26.1 mg/dL | 1.45 mmol/L | 65.2 mg/dL | 3.62 mmol/L | | Allopurinol | 1.3 mg/dL | 91.9 µmol/L | 4.0 mg/dL | 294 µmol/L | | Amiodarone | 0.2 mg/dL | 2.6 µmol/L | 0.6 mg/dL | 8.92 µmol/L | | Ampicillin | 1.1 mg/dL | 29.1 µmol/L | 5.6 mg/dL | 152 µmol/L | | Ascorbic acid | 1.2 mg/dL | 68.5 µmol/L | 6.0 mg/dL | 342 µmol/L | | Atenolol | 0.1 mg/dL | 4.1 µmol/L | 1.0 mg/dL | 37.6 µmol/L | | Biotin | 10 ng/mL | 0.04 µmol/L | 300 ng/mL | 1.2 µmol/L | | Caffeine | 1.3 mg/dL | 64.4 µmol/L | 6.0 mg/dL | 308 µmol/L | | Captopril | 0.1 mg/dL | 4.6 µmol/L | 0.5 mg/dL | 23 µmol/L | | Cefoxitin | 12.63 mg/dL | 281 µmol/L | 69.5 mg/dL | 1546 µmol/L | | Cholesterol | NA** | NA | 300 mg/dL | 7.8 mmol/L | | Cinnarizine | 0.0285 mg/dL | 0.8 µmol/L | 2.5 mg/dL | 67.8 µmol/L | | Clopidogrel | 0.32 mg/dL | 9.9 µmol/L | 7.5 mg/dL | 233 µmol/L | | Cocaine | 0.05 mg/dL | 1.6 µmol/L | 1.0 mg/dL | 33 µmol/L | | Dextran 40 | 15 g/L | 375 µmol/L | 45 g/L | 1125 µmol/L | | Digitoxin | 17 ng/mL | 22.2 nmol/L | 60 ng/mL | 78.4 nmol/L | | Digoxin | 1.4 ng/mL | 1.8 nmol/L | 6.1 ng/mL | 7.8 nmol/L | | Diltiazem | 0.025 mg/dL | 0.55 µmol/L | 0.68 mg/dL | 15 µmol/L | | Disopyramide | 0.45 mg/dL | 10.4 µmol/L | 1.3 mg/dL | 29.5 µmol/L | | Dopamine | 0.04 mg/dL | 1.96 µmol/L | 0.11 mg/dL | 5.87 µmol/L | | Doxycycline | 1.1 mg/dL | 22.5 µmol/L | 3.2 mg/dL | 67.5 µmol/L | | Erythromycin | 1.1 mg/dL | 15 µmol/L | 6.0 mg/dL | 81.6 µmol/L | | Furosemide | 2.0 mg/dL | 60.4 µmol/L | 6.0 mg/dL | 181 µmol/L | | Ibuprofen | 4.0 mg/dL | 194.3 µmol/L | 50 mg/dL | 2425 µmol/L | | Isosorbide dinitrate | 50.1 ng/mL | 212 nmol/L | 150.2 ng/mL | 636 nmol/L | | Lisinopril | 0.01 mg/dL | 0.25 µmol/L | 0.33 mg/dL | 0.74 µmol/L | | Low MW Heparin | 0.85 U/mL | NA | 2.0 U/mL | NA | | Lovastatin | 17.2 ng/mL | 42.4 nmol/L | 80 ng/mL | 197.8 nmol/L | | Methotrexate | 50 mg/dL | 1.1 mmol/L | 91 mg/dL | 2 mmol/L | | Methyldopa | 0.48 mg/dL | 20.1 µmol/L | 1.69 mg/dL | 70.9 µmol/L | | Methylprednisolone | 1.65 mg/dL | 44 µmol/L | 4.0 mg/dL | 106.8 µmol/L | | Mexiletine | 0.15 mg/dL | 7 µmol/L | 0.48 mg/dL | 22.3 µmol/L | | Nicotine | 0.004 mg/dL | 0.2 µmol/L | 0.10 mg/dL | 6.2 µmol/L | | Nifedipine | 0.013 mg/dL | 361.3 nmol/L | 0.04 mg/dL | 1156.1 nmol/L | | Nitrofurantoin | 0.20 mg/dL | 8.4 µmol/L | 0.40 mg/dL | 16.8 µmol/L | | Nitroglycerine | 7.5 ng/mL | 33 nmol/L | 16 ng/mL | 704.5 nmol/L | | Phenobarbital | 2.5 mg/dL | 107.8 µmol/L | 10.0 mg/dL | 431.5 µmol/L | | Phenytoin | 1.36 mg/dL | 49.6 µmol/L | 5.43 mg/dL | 198 µmol/L | | Primidone | 1.1 mg/dL | 48.2 µmol/L | 4.0 mg/dL | 183.5 µmol/L | | Propranolol | 0.06 mg/dL | 1.93 µmol/L | 0.23 mg/dL | 7.71 µmol/L | | Protein, Albumin | NA** | NA | 6 g/dL | 60 g/L | | Protein, Gamma Globulin | 2.5 g/dL | NA | NA | NA | | Protein, Total | NA** | NA | 12 g/dL | NA | | Quinidine | 0.38 mg/dL | 11.7 µmol/L | 1.2 mg/dL | 37 µmol/L | | Simvastatin | 0.004 ug/mL | 0.01 µmol/L | 32 ug/mL | 76.5 µmol/L | | Theophylline | 1.25 mg/dL | 69.4 µmol/L | 4.0 mg/dL | 222.2 µmol/L | | Tissue plasminogen activator (TPA) | 0.52 µg/mL | NA | 2.3 µg/mL | NA | | Thyroxine | 0.23 mg/dL | 0.3 µmol/L | 0.6 mg/dL | 0.8 µmol/L | | Triglyceride | 500 mg/dL | NA | 1000 mg/dL | NA | | Trimethoprim | 1.25 mg/dL | 43.1 µmol/L | 4.0 mg/dL | 138.3 µmol/L | | Verapamil | 0.035 mg/dL | 0.8 µmol/L | 0.22 mg/dL | 4.4 µmol/L | | Warfarin | 0.20 mg/dL | 6.6 µmol/L | 1.0 mg/dL | 32.5 µmol/L | {9}------------------------------------------------ {10}------------------------------------------------ **Testing at low concentrations was not appropriate for these endogenous substances. ## ANALYTICAL SPECIFICITY Cross-reactivity was determined following the governing standard CLSI document EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition.Cross-reactivity was tested at cTnl concentration of range of 20-60 pg/mL in native lithium heparin pools as well as in the absence of cTnl. The cross-reactants were tested at a single concentration near the upper limit of its physiological concentration. TNIH assay results from the spiked samples were compared with those of unspiked control samples. Percent cross-reactivity is calculated as: % Cross-reactivity = [measured analyte] - [control analyte] x 100 [cross-reactant] | Cross-reactant | Amount ng/mL [µg/L] | Cross-reactivity ( %) | |---------------------|---------------------|-----------------------| | Cardiac Troponin T | 1000 | 0.003 | | Skeletal Troponin I | 1000 | 0.001 | | Tropomyosin | 1000 | ND | | Actin | 1000 | ND | | Troponin C | 1000 | ND | | Myosin Light Chain | 1000 | ND | | Myoglobin | 1000 | ND | | CK-MB | 1000 | ND | *ND= Not detectable #### HIGH DOSE HOOK EFFECT The high dose hook effect of the TNIH assay was assessed. Normal human lithium heparin plasma were spiked with calibrator antigen. A dilution series was created and tested. No hook effect was found at 1,000,000 pg/mL troponin on the Dimension Vista TNIH assay. {11}------------------------------------------------ ## DILUTION RECOVERY Dilution recovery was evaluated for plasma at 1:2 and 1:5 dilutions using CTNI SDIL as diluent. Native human plasma samples were pooled to obtain at least three unique patient samples with TNIH levels ≥75% of the measuring interval and at least two samples above the measuring interval. For samples above the assay measuring interval the expected or neat value was determined using a 1:2 dilution in normal human plasma. Testing supported use of the diluent for over-range samples. ## CALIBRATION STABILITY The calibration stability for the TNIH assay on the Dimension Vista was determined by reading the recovery of the calibrators, commercial QC, a low patient pool and a high pool over time. The p-value of the regression slope was determined. Passing results were a p-value greater than or equal to 0.05 or drift less than or equal to the LoQ or less than or equal to10% for values up to 20,000 pg/mL and less than or equal to 13% for values greater than 20,000 pg/mL. Calibration interval was measured to be 30 days. ## OPEN WELL STABILITY The open well stability for the TNIH assay on the Dimension Vista was determined by reading the recovery of the calibrators and a low patient pool. On the first day of the study reagent packs were opened on the system and analyte was measured over the desired time interval. The p-value of the regression slope was determined. Passing results were a p-value greater than or equal to 0.05 or drift less than or equal to the LoQ or less than or equal to10% for values up to 20,000 pg/mL and less than or equal to 13% for values greater than 20,000 pg/mL. The stability of the reagents opened onboard the instrument was 7 days per well set. ## SAMPLE STABILITY Separated samples are stable for 8 hours at room temperature and for 24 hours when stored at 2-8 °C. Samples can be frozen at or below -20 °C for up to 40 days in a nonfrost free freezer and at or below -70 ℃ for up to 1 year. A linear regression analysis of the observed Troponin % Bias value (Y-axis) versus time (X-axis) was completed for each matrix. The acceptance criteria were the lower bound of the one-sided 95% confidence interval of the regression line is ≤-10% and all individual data points had a bias of ≤ -20% when compared to time zero. {12}------------------------------------------------ Llithium heparin plasma specimens were collected from apparently healthy individuals from the United States who ranged in age from 22-91 years of age. Each specimen was frozen, thawed and assayed once. The 99th percentile values were determined using the non-parametric statistical method described in CLSI Guidance EP28-A3c. Sample type, gender, and age had no statistically significant effect on the 99th percentile. The combined gender and the more commonly used sample type of lithium heparin plasma were used to determine the overall observed 99th percentile of 58.9 pg/mL [ng/L]. Two female subjects had troponin values of approximately 400 pg/mL and 4700 pg/mL, and were considered to be outliers. These results were not included in the 99th percentile-determination. The 99th percentile values determined for lithium heparin plasma (female, male, and combined), are shown in the following table. The 90% confidence intervals demonstrate that there is no statistical basis for using separate 99th percentile values based on gender or sample type. | Sample Type | Gender | n | 99th Percentile pg/mL [ng/L] | 90% CIb pg/mL [ng/L] | |------------------------|----------|------|---------------------------------|-------------------------| | Lithium Heparin Plasma | Female | 1017 | 53.7 | 37.7 - 115.7 | | Lithium Heparin Plasma | Male | 1004 | 78.5 | 41.4 - 114.5 | | Lithium Heparin Plasma | Combined | 2021 | 58.9 | 42.2 - 82.3 | b confidence interval ## CLINICAL PERFORMANCE A prospective study was performed to assess diagnostic accuracy for approximately 2500 subjects in lithium heparin plasma sample types to evaluate clinical performance. Specimens were collected at 29 emergency departments across the United States, from subjects presenting with symptoms consistent with acute coronary syndrome (ACS). All subject diagnoses were adjudicated by panels of certified cardiologists and emergency physicians according to the Third Universal Definition Of Myocardial Infarction - consensus guideline endorsed by the European Society of Cardiology (ESC), the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), and the World Heart Federation (WHF). The observed AMI prevalence in this study was 13.0 %. The clinical concordance study evaluated clinical sensitivity, clinical specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Dimension Vista TNIH assay in terms of its correlation to the the diagnosis of AMI. The results were analyzed using the serial sampling time points collected during the emergency department visit. A positive is defined as a sample exceeding the 99th percentile cutoff at the particular time point. The results are presented using serial timed intervals {13}------------------------------------------------ analyzed according to the time of presentation to the emergency department. The pooled gender results based on time of presentation to the emergency department, calculated using the overall 99th percentile of 58.9 pg/mL, are summarized in Table 1. | | Sensitivity | | | Specificity | | | Positive Predictive Value | | | Negative Predictive Value | | | |---------------------------------------|-------------|-------|------------|-------------|-------|------------|------------------------------|-------|------------|------------------------------|-------|------------| | Time since presentation (hours) | n | % | 95% Cl | n | % | 95% Cl | n | % | 95% Cl | n | % | 95% Cl | | 0 - <1.5 | 138 | 79.0% | 71.4- 85.0 | 969 | 92.5% | 90.6- 94.0 | 182 | 59.9% | 52.6- 66.7 | 925 | 96.9% | 95.5- 97.8 | | ≥ 1.5 - < 2.5 | 238 | 89.9% | 85.4- 93.1 | 1646 | 91.2% | 89.7- 92.5 | 359 | 59.6% | 54.5- 64.6 | 1525 | 98.4% | 97.7- 98.9 | | ≥ 2.5 - < 3.5 | 199 | 90.5% | 85.6- 93.8 | 1377 | 90.6% | 89.0- 92.1 | 309 | 58.3% | 52.7- 63.6 | 1267 | 98.5% | 97.7- 99.0 | | ≥ 3.5 - < 4.5 | 146 | 93.2% | 87.9- 96.2 | 1097 | 90.9% | 89.0- 92.4 | 236 | 57.6% | 51.2- 63.8 | 1007 | 99.0% | 98.2- 99.5 | | ≥ 4.5 - < 6 | 69 | 94.2% | 86.0- 97.7 | 467 | 88.9% | 85.7- 91.4 | 117 | 55.6% | 46.5- 64.2 | 419 | 99.0% | 97.6- 99.6 | | ≥6 - < 9 | 191 | 92.7% | 88.1- 95.6 | 913 | 87.4% | 85.1- 89.4 | 292 | 60.6% | 54.9- 66.0 | 812 | 98.3% | 97.1- 99.0 | | ≥ 9 - 24 | 216 | 93.1% | 88.9- 95.7 | 837 | 85.5% | 83.0- 87.8 | 322 | 62.4% | 57.0- 67.5 | 731 | 97.9% | 96.6- 98.8 | | ≥ 24 | 64 | 93.8% | 85.0- 97.5 | 254 | 85.8% | 81.0- 89.6 | 96 | 62.5% | 52.5- 71.5 | 222 | 98.2% | 95.5- 99.3 | Table1: Pooled gender results based on time from presentation to the emergency department Results for females based on time of presentation to the emergency department, calculated using the female-specific 99th percentile of 53.7 pg/mL for plasma are summarized in Table 2. | Sensitivity | | | | | Specificity | | | Positive Predictive Value | | | Negative Predictive Value | | | |---------------------------------------|----|-------|------------|-----|-------------|------------|-----|------------------------------|------------|-----|------------------------------|------------|--| | Time since presentation (hours) | n | % | 95% Cl | n | % | 95% Cl | n | % | 95% Cl | n | % | 95% Cl | | | 0 - <1.5 | 42 | 83.3% | 69.4- 91.7 | 409 | 94.4% | 91.7- 96.2 | 58 | 60.3% | 47.5- 71.9 | 393 | 98.2% | 96.4- 99.1 | | | ≥ 1.5 - < 2.5 | 77 | 89.6% | 80.8- 94.6 | 727 | 92.3% | 90.1- 94.0 | 125 | 55.2% | 46.5- 63.6 | 679 | 98.8% | 97.7- 99.4 | | | ≥ 2.5 - < 3.5 | 71 | 94.4% | 86.4- 97.8 | 624 | 92.6% | 90.3- 94.4 | 113 | 59.3% | 50.1- 67.9 | 582 | 99.3% | 98.2- 99.7 | | | ≥ 3.5 - < 4.5 | 50 | 94.0% | 83.8- 97.9 | 489 | 91.4% | 88.6- 93.6 | 89 | 52.8% | 42.5- 62.8 | 450 | 99.3% | 98.1- 99.8 | | | ≥ 4.5 - < 6 | 27 | 96.3% | 81.7- 99.3 | 243 | 86.0% | 81.1- 89.8 | 60 | 43.3% | 31.6- 55.9 | 210 | 99.5% | 97.4- 99.9 | | | ≥6-<9 | 67 | 94.0% | 85.6- 97.7 | 379 | 88.1% | 84.5- 91.0 | 108 | 58.3% | 48.9- 67.2 | 338 | 98.8% | 97.0- 99.5 | | | ≥ 9 - 24 | 72 | 93.1% | 84.8- 97.0 | 345 | 89.0% | 85.2- 91.9 | 105 | 63.8% | 54.3- 72.4 | 312 | 98.4% | 96.3- 99.3 | | | > 24 | 28 | 96.4% | 82.3- 99.4 | 111 | 83.8% | 75.8- 89.5 | 45 | 60.0% | 45.5- 73.0 | 94 | 98.9% | 94.2- 99.8 | | Table 2: Results for females based on time from presentation to the emergency department Results for males based on time of presentation to the emergency department, calculated using the male-specific 99th percentile of 78.5 pg/mL for plasma are summarized in Table 3. {14}------------------------------------------------ | | Sensitivity | | | Specificity | | | Positive Predictive Value | | | Negative Predictive Value | | | |---------------------------------------|-------------|-------|------------|-------------|-------|------------|------------------------------|-------|------------|------------------------------|-------|------------| | Time since presentation (hours) | n | % | 95% Cl | n | % | 95% Cl | n | % | 95% Cl | n | % | 95% Cl | | 0 - <1.5 | 96 | 74.0% | 64.4- 81.7 | 560 | 92.5% | 90.0- 94.4 | 113 | 62.8% | 53.6- 71.2 | 543 | 95.4% | 93.3- 96.9 | | ≥ 1.5 - < 2.5 | 161 | 84.5% | 78.1- 89.3 | 919 | 91.8% | 89.9- 93.4 | 211 | 64.5% | 57.8- 70.6 | 869 | 97.1% | 95.8- 98.0 | | ≥ 2.5 - < 3.5 | 128 | 85.2% | 78.0- 90.3 | 753 | 90.4% | 88.1- 92.3 | 181 | 60.2% | 52.9- 67.1 | 700 | 97.3% | 95.8- 98.3 | | ≥ 3.5 - < 4.5 | 96 | 86.5% | 78.2- 91.9 | 608 | 92.4% | 90.1- 94.3 | 129 | 64.3% | 55.8- 72.1 | 575 | 97.7% | 96.2- 98.7 | | ≥ 4.5 - < 6 | 42 | 88.1% | 75.0- 94.8 | 224 | 92.0% | 87.7- 94.9 | 55 | 67.3% | 54.1- 78.2 | 211 | 97.6% | 94.6- 99.0 | | ≥6 - < 9 | 124 | 87.9% | 81.0- 92.5 | 534 | 90.6% | 87.9- 92.8 | 159 | 68.6% | 61.0- 75.3 | 499 | 97.0% | 95.1- 98.2 | | ≥ 9 - 24 | 144 | 90.3% | 84.3- 94.1 | 492 | 87.2% | 84.0- 89.9 | 193 | 67.4% | 60.5- 73.6 | 443 | 96.8% | 94.8- 98.1 | | ≥ 24 | 36 | 88.9% | 74.7- 95.6 | 143 | 91.6% | 85.9- 95.1 | 44 | 72.7% | 58.2- 83.7 | 135 | 97.0% | 92.6- 98.8 | Table 3: Results for males based on time from presentation to the emergency department ## CONCLUSION The Dimension Vista High-Sensitivity Troponin I (TNIH) Assay is substantially equivalent to the Elecsys Troponin T Gen 5 STAT (K162895) in principle and performance based on the similarity of device designs and function demonstrated through performance attributes presented.