(415 days)
Not Found
No
The summary describes a standard immunoassay for measuring cardiac troponin I. There is no mention of AI or ML in the device description, intended use, or performance studies. The performance studies focus on traditional analytical and clinical validation methods for an immunoassay.
No.
This device is an in vitro diagnostic (IVD) assay designed to quantitatively measure cardiac troponin I levels, which is used to aid in the diagnosis of acute myocardial infarction. It is not directly used for treatment or therapy.
Yes
The device measures cardiac troponin I to aid in the diagnosis of acute myocardial infarction, which is a diagnostic purpose.
No
The device description clearly outlines physical components including reagents and calibrators, which are not software. The performance studies also focus on the analytical performance of these physical components.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the assay is for the "quantitative measurement of cardiac troponin I in human serum or plasma... using the Atellica IM Analyzer." It also states that the assay is used "to aid in the diagnosis of acute myocardial infarction (AMI)." This clearly indicates that the device is intended to be used in vitro (outside the body) to examine specimens from the human body for the purpose of providing information for diagnosis.
- Device Description: The description details the components of the assay, which are reagents and calibrators used to perform a chemical test on a biological sample (serum or plasma). This is characteristic of an IVD.
- Methodology: The methodology is Chemiluminescence and Sandwich immunoassay, which are common techniques used in IVD assays to detect and quantify specific substances in biological samples.
- Performance Studies: The document describes extensive performance studies, including precision, linearity, detection limit, interference, and clinical studies evaluating diagnostic accuracy. These types of studies are required for IVD devices to demonstrate their analytical and clinical performance.
- Predicate Device: The mention of a predicate device (K162895; Elecsys Troponin T Gen 5 STAT Immunoassay) is a strong indicator that this device is being submitted for regulatory review as an IVD, as predicate devices are used for comparison in the regulatory process for new IVDs.
All of these factors align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Atellica IM High-Sensitivity Troponin I (TnIH) assay is for in the quantitative measurement of cardiac troponin I in human serum or plasma (lithium heparin) using the Atellica IM Analyzer. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
Product codes
MMI
Device Description
The Atellica IM TnlH assay components include: Atellica IM TnIH Primary Reagent ReadyPack (with Lite Reagent and Solid Phase Reagent), and Atellica IM TnIH Calibrator (with High Calibrator (Cal H) and Low Calibrator (Cal L)).
The Lite Reagent contains Bovine serum albumin (BSA) conjugated to a recombinant monoclonal (sheep) Fab anti-human cTnl (~0.2-0.4 µg/mL) labeled with acridinium ester in HEPES buffer; stabilizers; preservatives.
The Solid Phase Reagent contains Streptavidin-coated magnetic latex particles (0.45 mg/mL) with 2 biotinylated (mouse and sheep) monoclonal anti-troponin I antibodies in buffer; stabilizers; preservatives.
The High Calibrator (Cal H) contains Human serum; human cTnl; preservatives.
The Low Calibrator (Cal L) contains HEPES buffer; bovine serum albumin (BSA); surfactants; preservatives.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision Study: A 20-day precision study was performed according to CLSI EP5-A3. Samples included eight (8) samples (4 serum; 4 lithium heparin plasma) from AMI patients, diluted with native serum or lithium heparin plasma from healthy subjects. Samples were assayed twice a day in replicates of 2, for 20 days (n = 80 replicates per sample). Testing was performed on 2 instruments. Representative results showed low %CV for both serum and lithium heparin plasma samples across varying concentrations (e.g., for Serum 1, Mean = 12.72 pg/mL, Repeatability %CV = 4.3, Within-Lab %CV = 4.7; for Lithium Heparin Plasma 4, Mean = 12862.97 pg/mL, Repeatability %CV = 1.7, Within-Lab %CV = 2.3).
Linearity Studies: Two linearity studies were performed according to CLSI EP06-A, each using 9 samples prepared by mixing a high-spiked cTnl sample with a low cTnl sample. The first study spanned the assay range, and the second ranged to ~150 pg/mL. Each study was tested with lithium heparin plasma and serum. The mean was taken from each sample tested in duplicate. Deviations from linear fit were generally small (e.g., for Lithium Heparin Full Range, deviation from -4.58% to 3.26%; for Serum Full Range, deviation from -6.46% to 7.47%).
Dilution Recovery: Eight (8) native AMI samples (>25000 pg/mL) were diluted 1:2 and 1:5. Recoveries for individual samples were all within 20%. Mean recovery for 1:2 dilutions was 99.6%, and for 1:5 dilutions was 91.6%.
Hook Effect: No hook effect was observed up to 500,000 pg/mL.
Detection Limit: LoB = 0.50 pg/mL; LoD = 1.60 pg/mL; LoQ = 2.50 pg/mL.
Endogenous Interference: Studies performed according to CLSI EP07-A2. Sample pools (~60 pg/mL cTnl) were spiked with potential interferents. For substances causing >10% interference, serial measurements were taken. All listed endogenous substances (Bilirubin, Biotin, Cholesterol, Hemoglobin, Protein, Triglycerides) showed
§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.
(a)
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.(b)
Classification. Class II.
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and 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.
July 19, 2018
Siemens Healthcare Diagnostics Inc. Matthew Gee Senior Manager, Regulatory Affairs 511 Benedict Avenue Tarrytown, NY 10591
Re: K171566
Trade/Device Name: Atellica IM High-Sensitivity Troponin I (TnIH) Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: June 26, 2018 Received: June 27, 2018
Dear Matthew Gee:
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. 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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
1
Part 820); 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 mediation-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) K171566
Device Name
Atellica IM High-Sensitivity Troponin I (TnIH)
Indications for Use (Describe)
The Atellica IM High-Sensitivity Troponin I (TnIH) assay is for in the quantitative measurement of cardiac troponin I in human serum or plasma (lithium heparin) using the Atellica IM Analyzer. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | ☑ |
|---|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) | ☐ |
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3
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990.
The assigned 510(k) Number is: K171566
Date Prepared 1.
July 13, 2018
Applicant Information 2.
| Contact: | Matthew Gee, M.Sc.
Senior Manager, Regulatory Affairs |
|----------|---------------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics Inc
511 Benedict Avenue
Tarrytown, NY 10591-5097 |
| Phone: | 914-255-8782 |
| Fax: | 914-524-3579 |
Email: matthew.gee@siemens.com
3. Regulatory Information
Table 1. Regulatory Information for Atellica IM High-Sensitivity Troponin I (TnIH)
| Trade Name | Atellica® IM High-Sensitivity Troponin I (TnIH) |
|---|---|
| Model Numbers | 10997840 (1-pack); 10997841 (5-pack) |
| Common Name | Immunoassay Method, Troponin Subunit |
| Regulation Number | 862.1215 |
| Regulation Description | Creatine phosphokinase /creatine kinase or isoenzymes test system |
| Product Code | MMI |
| FDA Classification | Class II |
| Review Panel | Clinical Chemistry (75) |
Predicate Device Information 4.
Predicate Device Name: Elecsys Troponin T Gen 5 STAT Immunoassay
510(k) Number: K162895
Intended Use / Indications for Use 5.
The Atellica® IM High-Sensitivity Troponin I (TnIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human serum or plasma (lithium heparin) using the Atellica® IM Analyzer. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
Device Description 6.
Table 2. Summary of Ingredients of the Atellica IM TnlH Assay Components
4
510(k) Summary of Safety and Effectiveness
| Component | Volume | Ingredients |
|---|---|---|
| Atellica IM TnIH Primary Reagent ReadyPack (included in assay kit) | ||
| Atellica IM TnIH | ||
| Lite Reagent | 8.0 mL/pack | Bovine serum albumin (BSA) conjugated to a |
| recombinant monoclonal (sheep) Fab anti-human cTnl | ||
| (~0.2-0.4 µg/mL) labeled with acridinium ester in | ||
| HEPES buffer; stabilizers; preservatives | ||
| Atellica IM TnIH | ||
| Solid Phase Reagent | 13.0 mL/pack | Streptavidin-coated magnetic latex particles (0.45 |
| mg/mL) with 2 biotinylated (mouse and sheep) | ||
| monoclonal anti-troponin I antibodies in buffer; | ||
| stabilizers; preservatives | ||
| Atellica IM TnIH Calibrator (included in assay kit) | ||
| Atellica IM TnIH | ||
| High Calibrator (Cal H) | 1.0 mL/vial | |
| (lyophilized) | Human serum; human cTnl; preservatives | |
| Atellica IM TnIH | ||
| Low Calibrator (Cal L) | 1.0 mL/vial | HEPES buffer; bovine serum albumin (BSA); |
| surfactants; preservatives |
Purpose of the Submission 7.
The purpose of this premarket notification is to submit a new device (Atellica IM TnIH) to FDA for consideration for clearance.
8. Comparison of Predicate Device and Modified Device
| Item | Atellica IM TnIH
(Candidate Device) | Elecsys Troponin T Gen 5 STAT
Immunoassay
(Predicate Device) |
|-----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The Atellica® IM High-Sensitivity
Troponin I (TnIH) assay is for in vitro
diagnostic use in the quantitative
measurement of cardiac troponin I
in human serum or plasma using the
Atellica® IM Analyzer. The assay can
be used to aid in the diagnosis of
acute myocardial infarction (AMI). | Immunoassay for the in vitro
quantitative determination of
cardiac troponin T (cTnT) in
lithium heparin plasma. The
immunoassay is intended to aid in
the diagnosis of myocardial
infarction. The
electrochemiluminescence
immunoassay "ECLIA" is intended
for use on the cobas system
analyzers. |
| Indications
for Use | The assay can be used to aid in the
diagnosis of acute myocardial infarction
(AMI). | The immunoassay is intended to
aid in the diagnosis of myocardial
infarction. |
| Methodology | Chemiluminescence | Electrochemiluminescence |
| Assay Protocol | Sandwich immunoassay | Same |
| Analyte | Cardiac troponin I | Cardiac troponin T |
| Specimen Type | Lithium heparin plasma and serum | Lithium heparin plasma |
| Lower Limit of
Measuring Range | LoQ | Same |
Table 3. Comparison of Atellica IM TnIH Assay to Predicate
5
| Item | Atellica IM TnIH
(Candidate Device) | Elecsys Troponin T Gen 5 STAT
Immunoassay
(Predicate Device) |
|---------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------|
| Measuring Range | 2.50-25,000 pg/mL (ng/L) | 6.0-10,000 pg/mL (ng/L) |
| Upper 99th
Percentile Cutoff | Female-Lithium Heparin: 34.11 pg/mL
Male-Lithium Heparin: 53.48 pg/mL
Combined-Lithium Heparin: 45.20 pg/mL
Female-Serum: 38.64 pg/mL
Male-Serum: 53.53 pg/mL
Combined-Serum: 45.43 pg/mL
Overall: 45.20 pg/mL | Female: 14 pg/mL (ng/L)
Male: 22 pg/mL (ng/L)
Combined: 19 pg/mL (ng/L) |
| Calibration | 2-point calibration | Same |
Table 3. Comparison of Atellica IM TnIH Assay to Predicate
9. Standard/Guidance Document References
The following recognized standards from Clinical Laboratory Standards Institute (CLSI) were used as a basis of the study procedures described in this submission:
- Evaluation of Precision Performance of Quantitative Measurement Methods; ■ Approved Guideline – Third Edition (CLSI EP05-A3, 2014; Recognition No. 7-251)
- I Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline (CLSI EP06-A, 2003; Recognition No. 7-193)
- l Interference Testing in Clinical Chemistry; Approved Guideline - Second Edition (CLSI EP07-A2, 2005; Recognition No. 7-127)
- I Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition (CLSI EP17-A2, 2012; Recognition No. 7-233)
- I Defining. Establishing and Verifying Reference Intervals in the Clinical Laboratory: Approved Guideline - Third Edition (CLSI EP28-A3c - formerly C28-A3c, 2010; Recognition No. 7-224)
- l Medical devices – Application of risk management to medical devices (ANSI/AAMI/ISO 14971:2007/(R)2010; Recognition No. 5-70)
6
10. Performance Characteristics
10.1 Precision
A 20-day precision study was performed according to CLSI EP5-A3. Samples included eight (8) samples (4 serum; 4 lithium heparin plasma) from AMI patients. These samples were diluted with native serum or lithium heparin plasma from healthy subjects. Samples were assayed twice a day in replicates of 2, for 20 days (n = 80 replicates per sample). Testing was performed on 2 instruments. The following are representative of the results obtained:
| Sample | Mean | Repeatability | Within-Lab | ||
|---|---|---|---|---|---|
| (pg/mL) | SD | ||||
| (pg/mL) | %CV | SD | |||
| (pg/mL) | %CV | ||||
| Serum 1 | 12.72 | 0.55 | 4.3 | 0.59 | 4.7 |
| Serum 2 | 127.93 | 2.30 | 1.8 | 3.09 | 2.4 |
| Serum 3 | 1334.97 | 22.28 | 1.7 | 27.48 | 2.1 |
| Serum 4 | 13815.89 | 192.05 | 1.4 | 266.91 | 1.9 |
| Lithium Heparin Plasma 1 | 12.03 | 0.49 | 4.1 | 0.64 | 5.3 |
| Lithium Heparin Plasma 2 | 131.21 | 2.23 | 1.7 | 2.75 | 2.1 |
| Lithium Heparin Plasma 3 | 1363.38 | 27.11 | 2.0 | 32.00 | 2.3 |
| Lithium Heparin Plasma 4 | 12862.97 | 212.91 | 1.7 | 291.00 | 2.3 |
10.2 Linearity
Two linearity studies were performed according to CLSI EP06-A, each using 9 samples prepared by mixing a high-spiked cTnl sample with a low cTnl sample. The first study spanned the assay range and the second study ranged to ~150 pg/mL. Each study was tested with lithium heparin plasma and serum. The mean was taken from each sample tested in duplicate. The following are representative of the results obtained:
| Sample | Deviation from Linear Fit (% or pg/mL) | |||
|---|---|---|---|---|
| Li Hep | ||||
| Full Range | Serum | |||
| Full Range | Li Hep | |||
| ~150 pg/mL | Serum | |||
| ~150 pg/mL | ||||
| A | -0.53% | 0.27% | 2.23% | 0.73% |
| B | 3.26% | -6.46% | -0.07% | -0.04% |
| C | 2.08% | -4.50% | -0.11% | -0.06% |
| D | 0.78% | -2.95% | -0.09% | -0.05% |
| E | -0.01% | -0.27% | -0.04% | -0.03% |
| F | -1.40% | 1.20% | 0.01% | -0.01% |
| G | -2.49% | 3.24% | 0.07% | 0.01% |
| H | -3.50% | 5.43% | 0.13% | 0.03% |
| I | -4.58% | 7.47% | 0.19% | 0.06% |
7
10.3 Dilution Recovery
Eight (8) native AMI samples (4 lithium heparin plasma and 4 serum) measuring above the analytical measuring range (i.e. >25000 pg/mL) were diluted to 1:2 and 1:5 with Multi-Diluent 11. Recoveries for individual samples were all within 20%. The mean of all 1:2 dilutions was 99.6%. The mean of all 1:5 dilutions was 91.6%.
10.4 Hook Effect
A study was performed to evaluate hook effect. There is no hook effect with the Atellica IM TnIH assay up to 500,000 pg/mL.
10.5 Detection Limit
The limit of blank (LoB), limit of detection (LoD), and the limit of quantitation (LoQ) were determined as described in CLSI protocol EP17-A2. The Atellica IM TnIH assay has an LoB of 0.50 pg/mL, an LoD of 1.60 pg/mL, and an LoQ of 2.50 pg/mL.
The LoB is defined as the highest measurement result that is likely to be observed for a blank sample. The LoD is defined as the lowest concentration of cardiac troponin I that can be detected with 95% probability. The LoQ is defined as the lowest concentration of cardiac troponin I that can be detected at a total CV of 20%.
10.6 Endogenous Interference
Endogenous interference studies were performed according to CLSI EP07-A2. Sample pools for each matrix (~60 pg/mL cTnl) were spiked with potential interferents. Control samples were prepared by spiking sample pools with the appropriate diluent at the same volume as the interfering substance stock. For substances spiked at doses that caused >10% interference, serial measurements were taken and analyzed by linear regression. Results are presented below.
| Endogenous Substance | Matrix | Control
Dose
(pg/mL) | Test
Dose
(pg/mL) | % Interference |
|--------------------------------------|--------|----------------------------|-------------------------|----------------|
| Bilirubin (Conjugated)
40 mg/dL | Li Hep | 58.08 | 57.14 | -1.61% |
| | Serum | 59.24 | 57.95 | -2.17% |
| Bilirubin (Unconjugated)
60 mg/dL | Li Hep | 58.78 | 58.75 | -0.06% |
| | Serum | 58.87 | 58.26 | -1.04% |
| Biotin
3500 ng/mL | Li Hep | 59.16 | 58.86 | -0.51% |
| | Serum | 59.40 | 59.57 | 0.28% |
| Cholesterol
500 mg/dL | Li Hep | 50.33 | 51.90 | 3.12% |
| | Serum | 51.45 | 51.47 | 0.04% |
| Hemoglobin
500 mg/dL | Li Hep | 57.29 | 56.55 | -1.29% |
| | Serum | 58.10 | 55.31 | -4.81% |
| Protein (Albumin)
6 g/dL | Li Hep | 57.57 | 56.18 | -2.40% |
| | Serum | 57.64 | 58.36 | 1.25% |
| Protein (Gamma Globulin)
2.5 g/dL | Li Hep | 53.44 | 53.28 | -0.30% |
| | Serum | 52.68 | 54.78 | 3.99% |
| Protein (Total)
12 g/dL | Li Hep | 54.89 | 57.35 | 4.48% |
| | Serum | 57.04 | 56.33 | -1.25% |
| Triglycerides
2000 mg/dL | Li Hep | 51.83 | 52.05 | 0.43% |
| | Serum | 52.20 | 51.84 | -0.70% |
8
10.7 Drug Interference
Therapeutic drug interference studies were performed according to CLSI EP07-A2. Sample pools (~60 pq/mL cTnl) for each matrix were tested. Control samples were prepared by spiking sample pools with the appropriate diluent at the same volume as the interfering substance stock. At the tested concentrations, all drugs caused 1 Apple FS, Sandoval Y, Jaffe AS, et al. Cardiac troponin assays: Guide to understanding analytical characteristics and their impact on clinical care. Clin Biochem 2017;63:73-81.
11
10.13 Clinical Studies
A clinical performance study was conducted to evaluate the diagnostic accuracy of the Atellica IM TnIH assay in terms of the clinical concordance between the 90th percentile cutoff and the presence or absence of an adjudicated acute myocardial infarction (AMI) diagnosis. Specimens were collected at 29 sites from different regions across the United States. Testing of specimens was performed at 3 sites.
In this study, the sites enrolled all patients who presented to the emergency department, or ambulatory care center equivalent, with signs or symptoms suspicious for a possible acute coronary syndrome (ACS) event. The diagnosis of AMI was performed by an independent adjudication committee which included cardiologists. The adjudication was based on 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 clinical concordance study evaluated clinical sensitivity, clinical specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Atellica IM TnlH assay in terms of its correlation to the diagnosis of AMI.
Results were analyzed according to time from presentation to the emergency department.
| Sensitivity | Specificity | PPV | NPV | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Matrix | Timepoint | N | Estimate | 95% CI | N | Estimate | 95% CI | N | Estimate | 95% CI | N | Estimate | 95% CI |
| Li Hep | |||||||||||||
| Plasma | 0-1.5hr | 45 | 84.4% | 71.2-92.3 | 401 | 93.5% | 90.7-95.5 | 64 | 59.4% | 47.1-70.5 | 382 | 98.2% | 96.3-99.1 |
| ≥1.5-2.5 hr | 79 | 89.9% | 81.3-94.8 | 720 | 91.8% | 89.6-93.6 | 130 | 54.6% | 46.0-62.9 | 669 | 98.8% | 97.7-99.4 | |
| ≥2.5-3.5 hr | 73 | 94.5% | 86.7-97.8 | 621 | 91.6% | 89.2-93.6 | 121 | 57.0% | 48.1-65.5 | 573 | 99.3% | 98.2-99.7 | |
| ≥3.5-4.5 hr | 50 | 94.0% | 83.8-97.9 | 487 | 89.5% | 86.5-91.9 | 98 | 48.0% | 38.3-57.7 | 439 | 99.3% | 98.0-99.8 | |
| ≥4.5-6 hr | 26 | 96.2% | 81.1-99.3 | 238 | 87.0% | 82.1-90.7 | 56 | 44.6% | 32.4-57.6 | 208 | 99.5% | 97.3-99.9 | |
| ≥6-9 hr | 69 | 94.2% | 86.0-97.7 | 374 | 88.0% | 84.3-90.9 | 110 | 59.1% | 49.7-67.8 | 333 | 98.8% | 97.0-99.5 | |
| ≥9-24 hr | 74 | 94.6% | 86.9-97.9 | 342 | 87.4% | 83.5-90.5 | 113 | 61.9% | 52.7-70.4 | 303 | 98.7% | 96.7-99.5 | |
| ≥24 hr | 27 | 96.3% | 81.7-99.3 | 110 | 80.9% | 72.6-87.2 | 47 | 55.3% | 41.2-68.6 | 90 | 98.9% | 94.0-99.8 | |
| Serum | 0-1.5hr | 42 | 81.0% | 66.7-90.0 | 407 | 93.6% | 90.8-95.6 | 60 | 56.7% | 44.1-68.4 | 389 | 97.9% | 96.0-99.0 |
| ≥1.5-2.5 hr | 77 | 89.6% | 80.8-94.6 | 721 | 92.0% | 89.7-93.7 | 127 | 54.3% | 45.7-62.7 | 671 | 98.8% | 97.7-99.4 | |
| ≥2.5-3.5 hr | 67 | 92.5% | 83.7-96.8 | 619 | 92.4% | 90.0-94.2 | 109 | 56.9% | 47.5-65.8 | 577 | 99.1% | 98.0-99.6 | |
| ≥3.5-4.5 hr | 48 | 93.8% | 83.2-97.9 | 484 | 90.3% | 87.3-92.6 | 92 | 48.9% | 38.9-59.0 | 440 | 99.3% | 98.0-99.8 | |
| ≥4.5-6 hr | 26 | 96.2% | 81.1-99.3 | 236 | 87.7% | 82.9-91.3 | 54 | 46.3% | 33.7-59.4 | 208 | 99.5% | 97.3-99.9 | |
| ≥6-9 hr | 63 | 95.2% | 86.9-98.4 | 378 | 88.6% | 85.0-91.4 | 103 | 58.3% | 48.6-67.3 | 338 | 99.1% | 97.4-99.7 | |
| ≥9-24 hr | 73 | 94.5% | 86.7-97.8 | 342 | 89.5% | 85.8-92.3 | 105 | 65.7% | 56.2-74.1 | 310 | 98.7% | 96.7-99.5 | |
| ≥24 hr | 26 | 96.2% | 81.1-99.3 | 111 | 82.9% | 74.8-88.8 | 44 | 56.8% | 42.2-70.3 | 93 | 98.9% | 94.2-99.8 |
Using the female-specific 99th percentiles for lithium heparin plasma (34.11 pg/mL) and serum (38.64 pg/mL), the following results were obtained.
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| Using the male-specific 99th percentiles for lithium heparin plasma (53.48 pg/mL) and serum | ||
|---|---|---|
| (53.53 pg/mL), the following results were obtained. |
| Sensitivity | Specificity | PPV | NPV | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Matrix | Timepoint | N | Estimate | 95% CI | N | Estimate | 95% CI | N | Estimate | 95% CI | N | Estimate | 95% CI |
| Li Hep | |||||||||||||
| Plasma | 0-1.5hr | 100 | 75.0% | 65.7-82.5 | 563 | 91.5% | 88.9-93.5 | 123 | 61.0% | 52.1-69.1 | 540 | 95.4% | 93.3-96.8 |
| ≥1.5-2.5 hr | 161 | 87.6% | 81.6-91.8 | 905 | 91.2% | 89.1-92.8 | 221 | 63.8% | 57.3-69.9 | 845 | 97.6% | 96.4-98.5 | |
| ≥2.5-3.5 hr | 128 | 89.8% | 83.4-94.0 | 748 | 90.0% | 87.6-91.9 | 190 | 60.5% | 53.4-67.2 | 686 | 98.1% | 96.8-98.9 | |
| ≥3.5-4.5 hr | 99 | 90.9% | 83.6-95.1 | 593 | 92.2% | 89.8-94.1 | 136 | 66.2% | 57.9-73.6 | 556 | 98.4% | 97.0-99.1 | |
| ≥4.5-6 hr | 40 | 92.5% | 80.1-97.4 | 223 | 90.6% | 86.0-93.8 | 58 | 63.8% | 50.9-74.9 | 205 | 98.5% | 95.8-99.5 | |
| ≥6-9 hr | 124 | 91.1% | 84.8-95.0 | 531 | 88.5% | 85.5-91.0 | 174 | 64.9% | 57.6-71.6 | 481 | 97.7% | 96.0-98.7 | |
| ≥9-24 hr | 141 | 93.6% | 88.3-96.6 | 493 | 85.6% | 82.2-88.4 | 203 | 65.0% | 58.2-71.3 | 431 | 97.9% | 96.1-98.9 | |
| ≥24 hr | 35 | 91.4% | 77.6-97.0 | 143 | 88.1% | 81.8-92.4 | 49 | 65.3% | 51.3-77.1 | 129 | 97.7% | 93.4-99.2 | |
| Serum | 0-1.5hr | 98 | 77.6% | 68.3-84.7 | 573 | 91.6% | 89.1-93.6 | 124 | 61.3% | 52.5-69.4 | 547 | 96.0% | 94.0-97.3 |
| ≥1.5-2.5 hr | 162 | 86.4% | 80.3-90.9 | 925 | 91.5% | 89.5-93.1 | 219 | 63.9% | 57.4-70.0 | 868 | 97.5% | 96.2-98.3 | |
| ≥2.5-3.5 hr | 128 | 87.5% | 80.7-92.2 | 765 | 89.9% | 87.6-91.9 | 189 | 59.3% | 52.1-66.0 | 704 | 97.7% | 96.3-98.6 | |
| ≥3.5-4.5 hr | 99 | 88.9% | 81.2-93.7 | 599 | 92.5% | 90.1-94.3 | 133 | 66.2% | 57.8-73.7 | 565 | 98.1% | 96.5-98.9 | |
| ≥4.5-6 hr | 38 | 94.7% | 82.7-98.5 | 218 | 90.8% | 86.3-94.0 | 56 | 64.3% | 51.2-75.5 | 200 | 99.0% | 96.4-99.7 | |
| ≥6-9 hr | 122 | 91.0% | 84.6-94.9 | 526 | 89.9% | 87.1-92.2 | 164 | 67.7% | 60.2-74.4 | 484 | 97.7% | 96.0-98.7 | |
| ≥9-24 hr | 140 | 93.6% | 88.2-96.6 | 499 | 85.6% | 82.2-88.4 | 203 | 64.5% | 57.7-70.8 | 436 | 97.9% | 96.1-98.9 | |
| ≥24 hr | 37 | 86.5% | 72.0-94.1 | 144 | 88.9% | 82.7-93.0 | 48 | 66.7% | 52.5-78.3 | 133 | 96.2% | 91.5-98.4 |
Using the overall 99th Percentile (45.20 pg/mL), the following results were obtained for both genders combined.
| Sensitivity | Specificity | PPV | NPV | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Matrix | Timepoint | N | Estimate | 95% CI | N | Estimate | 95% CI | N | Estimate | 95% CI | N | Estimate | 95% CI |
| Li Hep | |||||||||||||
| Plasma | 0-1.5hr | 145 | 77.2% | 69.8-83.3 | 964 | 91.9% | 90.0-93.5 | 190 | 58.9% | 51.8-65.7 | 919 | 96.4% | 95.0-97.4 |
| ≥1.5-2.5 hr | 240 | 90.0% | 85.6-93.2 | 1625 | 90.6% | 89.1-92.0 | 368 | 58.7% | 53.6-63.6 | 1497 | 98.4% | 97.6-98.9 | |
| ≥2.5-3.5 hr | 201 | 92.0% | 87.5-95.0 | 1369 | 90.6% | 88.9-92.0 | 314 | 58.9% | 53.4-64.2 | 1256 | 98.7% | 97.9-99.2 | |
| ≥3.5-4.5 hr | 149 | 92.6% | 87.3-95.8 | 1080 | 90.8% | 89.0-92.4 | 237 | 58.2% | 51.9-64.3 | 992 | 98.9% | 98.0-99.4 | |
| ≥4.5-6 hr | 66 | 97.0% | 89.6-99.2 | 461 | 89.2% | 86.0-91.7 | 114 | 56.1% | 47.0-64.9 | 413 | 99.5% | 98.3-99.9 | |
| ≥6-9 hr | 193 | 92.7% | 88.2-95.6 | 905 | 87.6% | 85.3-89.6 | 291 | 61.5% | 55.8-66.9 | 807 | 98.3% | 97.1-99.0 | |
| ≥9-24 hr | 215 | 94.0% | 89.9-96.4 | 835 | 86.6% | 84.1-88.7 | 314 | 64.3% | 58.9-69.4 | 736 | 98.2% | 97.0-99.0 | |
| ≥24 hr | 62 | 93.5% | 84.6-97.5 | 253 | 83.4% | 78.3-87.5 | 100 | 58.0% | 48.2-67.2 | 215 | 98.1% | 95.3-99.3 | |
| Serum | 0-1.5hr | 140 | 78.6% | 71.1-84.6 | 980 | 92.2% | 90.4-93.8 | 186 | 59.1% | 52.0-65.9 | 934 | 96.8% | 95.5-97.7 |
| ≥1.5-2.5 hr | 239 | 87.9% | 83.1-91.4 | 1646 | 91.0% | 89.5-92.3 | 358 | 58.7% | 53.5-63.6 | 1527 | 98.1% | 97.3-98.7 | |
| ≥2.5-3.5 hr | 195 | 90.8% | 85.9-94.1 | 1384 | 90.8% | 89.1-92.2 | 305 | 58.0% | 52.4-63.4 | 1274 | 98.6% | 97.8-99.1 | |
| ≥3.5-4.5 hr | 147 | 91.2% | 85.5-94.8 | 1083 | 91.0% | 89.1-92.5 | 232 | 57.8% | 51.3-63.9 | 998 | 98.7% | 97.8-99.2 | |
| ≥4.5-6 hr | 64 | 96.9% | 89.3-99.1 | 454 | 89.6% | 86.5-92.1 | 109 | 56.9% | 47.5-65.8 | 409 | 99.5% | 98.2-99.9 | |
| ≥6-9 hr | 185 | 93.5% | 89.0-96.3 | 904 | 88.7% | 86.5-90.6 | 275 | 62.9% | 57.1-68.4 | 814 | 98.5% | 97.4-99.2 | |
| ≥9-24 hr | 213 | 93.9% | 89.8-96.4 | 841 | 86.7% | 84.2-88.8 | 312 | 64.1% | 58.6-69.2 | 742 | 98.2% | 97.0-99.0 | |
| ≥24 hr | 63 | 90.5% | 80.7-95.6 | 255 | 85.5% | 80.6-89.3 | 94 | 60.6% | 50.5-69.9 | 224 | 97.3% | 94.3-98.8 |
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10.14 Traceability and Value Assignment
The Atellica IM TnIH assay is standardized to an internal standard manufactured using human heart homogenate. Assigned values for calibrators are traceable to this standardization.
10.15 Stability
The Atellica IM TnIH reagents and calibrators are stable until the date printed on the box label when stored at 2-8°C.
The onboard stability of the Atellica IM TnIH reagents is 28 days with a pack calibration interval of 31 days, and a lot calibration interval of 47 days.
Conclusions 11.
The Atellica IM High-Sensitivity Troponin I (TNIH) assay (Reagents and Calibrators) is substantially equivalent in principle and performance to the currently-marketed predicate device, the Elecsys Troponin T Gen 5 STAT Immunoassay, cleared under 510(k) K162895.