(437 days)
Not Found
No
The description details a chemiluminescence immunoassay for measuring cardiac troponin I. There is no mention of AI or ML in the device description, intended use, performance studies, or key metrics. The analysis focuses on traditional analytical and clinical performance characteristics of an in vitro diagnostic assay.
No.
The device is an in vitro diagnostic (IVD) assay designed to quantitatively measure cardiac troponin I to aid in the diagnosis of acute myocardial infarction. It does not treat, prevent, or mitigate disease.
Yes
The device quantitatively measures cardiac troponin I in human serum or plasma to aid in the diagnosis of acute myocardial infarction (AMI), which is a diagnostic purpose.
No
The device is an in vitro diagnostic assay kit which includes reagents and calibrators, clearly indicating it is not a software-only medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states "for in vitro diagnostic use".
- Measurement of Biomarkers: The device measures cardiac troponin I in human serum or plasma, which are biological samples.
- Diagnostic Purpose: The assay is used "to aid in the diagnosis of acute myocardial infarction (AMI)". This indicates a diagnostic purpose.
- Device Description: The description details reagents and calibrators used to perform a test on biological samples.
- Performance Studies: The document describes clinical performance studies evaluating the diagnostic accuracy of the assay.
- Intended User: The "Intended User / Care Setting" section also states "in vitro diagnostic use".
All these points align with the definition of an In Vitro Diagnostic device, which is used to examine specimens from the human body to provide information for diagnostic, monitoring, or screening purposes.
N/A
Intended Use / Indications for Use
The ADVIA Centaur® 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 ADVIA Centaur XP system. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
Product codes
MMI
Device Description
The ADVIA Centaur TNIH assay kit includes:
- ADVIA Centaur TNIH Primary Reagent ReadyPack: Contains ADVIA Centaur TNIH Lite Reagent (Bovine serum albumin (BSA) conjugated to a recombinant monoclonal Fab anti-human cTnl (~0.2-0.4 µg/mL) labeled with acridinium ester in HEPES buffer with stabilizers and preservatives) and ADVIA Centaur TNIH Solid Phase Reagent (0.45 mg/mL streptavidin-coated magnetic latex particles with 2 biotinylated (mouse and sheep) monoclonal anti-troponin I antibodies in buffer with stabilizers and preservatives).
- ADVIA Centaur TNIH Calibrator: Includes ADVIA Centaur TNIH High Calibrator (Human serum with human cTnl and preservatives (lyophilized)) and ADVIA Centaur TNIH Low Calibrator (HEPES buffer with bovine serum albumin (BSA), surfactants, and preservatives (liquid)).
The methodology is chemiluminescence and the assay protocol is a sandwich immunoassay.
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
-
Precision Study:
- Study type: 20-day precision study performed according to CLSI EP5-A3.
- Sample size: Eight (8) samples (4 serum; 4 lithium heparin plasma) from AMI patients, diluted with native serum or lithium heparin plasma from healthy subjects. Each sample was assayed twice a day in replicates of 2, for 20 days (n = 80 replicates per sample).
- Key results: Repeatability and Within-Lab precision were evaluated, with %CVs generally below 5.4%. For example, Serum 1 (mean 13.11 pg/mL) had a Repeatability %CV of 4.8 and a Within-Lab %CV of 5.4.
-
Linearity Study:
- Study type: Two linearity studies performed according to CLSI EP06-A.
- Sample size: Each study used 9 samples prepared by mixing a high-spiked cTnl sample with a low cTnl sample. Tested with lithium heparin plasma and serum. Each sample was tested in duplicate with 3 lots.
- Key results: Deviations from linear fit generally ranged from approximately -5.86% to 6.57%.
-
Dilution Recovery Study:
- Sample size: Eight (8) native AMI samples (4 lithium heparin plasma and 4 serum) measuring above the analytical measuring range (>25000 pg/mL).
- Key results: Samples were diluted to 1:2 and 1:5 with Multi-Diluent 11. Recoveries for individual samples were all within 20%. Mean recovery for 1:2 dilutions was 102.6%, and for 1:5 dilutions was 91.8%.
-
Hook Effect Study:
- Key results: No hook effect was observed up to 500,000 pg/mL.
-
Detection Limit Study:
- Study type: Determined as described in CLSI protocol EP17-A2.
- Key results: Limit of Blank (LoB) of 0.50 pg/mL, Limit of Detection (LoD) of 1.60 pg/mL, and Limit of Quantitation (LoQ) of 2.50 pg/mL.
-
Endogenous Interference Study:
- Study type: Performed according to CLSI EP07-A2.
- Sample size: Sample pools (~60 pg/mL cTnl) spiked with potential interferents.
- Key results: Most endogenous substances (Bilirubin, Biotin, Cholesterol, Hemoglobin, Protein, Triglycerides) caused less than 5% interference.
-
Drug Interference Study:
- Study type: Performed according to CLSI EP07-A2.
- Sample size: Sample pools (~60 pg/mL cTnl) for each matrix.
- Key results: All tested drugs caused
§ 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
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July 12, 2018
Siemens Healthcare Diagnostics Inc. Matthew Gee Senior Manager, Regulatory Affairs 511 Benedict Avenue Tarrytown, NY 10591
Re: K171274
Trade/Device Name: ADVIA Centaur 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) K171274
Device Name
ADVIA Centaur High-Sensitivity Troponin I (TNIH)
Indications for Use (Describe)
The ADVIA Centaur 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 ADVIA Centaur XP 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) |
|---|
| ☑ 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: K171274
Date Prepared 1.
July 12, 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 ADVIA Centaur High-Sensitivity Troponin I (TNIH)
| Trade Name | ADVIA Centaur® High-Sensitivity Troponin I (TNIH) |
|---|---|
| Model Numbers | 10994774 (1-pack); 10994775 (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 ADVIA Centaur® 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 ADVIA Centaur XP system. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
4
6. Device Description
Table 2. Summary of Ingredients of the ADVIA Centaur TNIH Assay Components
| Component | Volume | Ingredients | ||
|---|---|---|---|---|
| ADVIA Centaur TNIH Primary Reagent ReadyPack (included in assay kit) | ||||
| ADVIA Centaur TNIH Lite 8.0 mL/pack | ||||
| Reagent | Bovine serum albumin (BSA) conjugated to a | |||
| recombinant monoclonal Fab anti-human cTnl (~0.2- | ||||
| 0.4 µg/mL) labeled with acridinium ester in HEPES | ||||
| buffer with stabilizers and preservatives | ||||
| ADVIA Centaur TNIH | ||||
| Solid Phase Reagent | 13.0 mL/pack | 0.45 mg/mL streptavidin-coated magnetic latex | ||
| particles with 2 biotinylated (mouse and sheep) | ||||
| monoclonal anti-troponin I antibodies in buffer with | ||||
| stabilizers and preservatives | ||||
| ADVIA Centaur TNIH Calibrator (included in assay kit) | ||||
| ADVIA Centaur TNIH | ||||
| High Calibrator | 1.0 mL/vial | Human serum with human cTnl and preservatives | ||
| (lyophilized) | ||||
| ADVIA Centaur TNIH | ||||
| Low Calibrator | 1.0 mL/vial | HEPES buffer with bovine serum albumin (BSA), | ||
| surfactants, and preservatives (liquid) |
Purpose of the Submission 7.
The purpose of this premarket notification is to submit a new device (ADVIA Centaur TNIH) to FDA for consideration for clearance.
8. Comparison of Predicate Device and Modified Device
Table 3. Comparison of ADVIA Centaur TNIH Assay to Predicate
| Item | ADVIA Centaur TNIH
(Candidate Device) | Elecsys Troponin T Gen 5 STAT
Immunoassay
(Predicate Device) |
|------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The ADVIA Centaur® 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
ADVIA Centaur XP system. 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 |
5
| Item | ADVIA Centaur TNIH
(Candidate Device) | Elecsys Troponin T Gen 5 STAT
Immunoassay
(Predicate Device) |
|-----------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------|
| Lower Limit of
Measuring Range | LoQ | Same |
| 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: 36.99 pg/mL
Male-Lithium Heparin: 57.27 pg/mL
Combined-Lithium Heparin: 47.34 pg/mL
Female-Serum: 39.59 pg/mL
Male-Serum: 58.05 pg/mL
Combined-Serum: 46.47 pg/mL
Overall: 47.34 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 ADVIA Centaur TNIH Assay to Predicate
Standard/Guidance Document References 9.
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)
- I 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)
- 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)
- I 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 | 13.11 | 0.63 | 4.8 | 0.70 | 5.4 |
| Serum 2 | 138.62 | 1.81 | 1.3 | 2.68 | 1.9 |
| Serum 3 | 1461.93 | 12.47 | 0.9 | 17.52 | 1.2 |
| Serum 4 | 14099.79 | 102.77 | 0.7 | 133.95 | 0.9 |
| Lithium Heparin Plasma 1 | 12.68 | 0.45 | 3.6 | 0.62 | 4.9 |
| Lithium Heparin Plasma 2 | 145.93 | 1.84 | 1.3 | 2.28 | 1.6 |
| Lithium Heparin Plasma 3 | 1522.05 | 13.56 | 0.9 | 21.32 | 1.4 |
| Lithium Heparin Plasma 4 | 13436.79 | 104.88 | 0.8 | 148.73 | 1.1 |
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. Testing was performed with 3 lots. 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 | 1.08% | 0.19% | -3.50% | -0.09 pg/mL |
| B | -5.41% | -5.86% | 0.45% | 3.13% |
| C | -3.71% | -4.12% | 0.40% | 1.57% |
| D | -2.29% | -2.75% | 0.30% | 0.30% |
| E | -0.13% | -0.43% | 0.18% | -0.52% |
| F | 1.16% | 0.80% | 0.06% | -0.81% |
| G | 2.99% | 2.69% | -0.07% | -0.59% |
| H | 4.73% | 4.49% | -0.19% | 0.14% |
| I | 6.57% | 6.39% | -0.32% | 1.44% |
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 102.6%. The mean of all 1:5 dilutions was 91.8%.
10.4 Hook Effect
A study was performed to evaluate hook effect. There is no hook effect with the ADVIA Centaur 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 ADVIA Centaur 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. These sample pools (~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 | 61.22 | 62.43 | 1.97% |
| Bilirubin (Conjugated)
40 mg/dL | Serum | 62.62 | 63.04 | 0.68% |
| Bilirubin (Unconjugated)
60 mg/dL | Li Hep | 61.10 | 61.38 | 0.46% |
| Bilirubin (Unconjugated)
60 mg/dL | Serum | 61.04 | 62.61 | 2.57% |
| Biotin
3500 ng/mL | Li Hep | 60.62 | 59.76 | -1.42% |
| Biotin
3500 ng/mL | Serum | 60.56 | 59.75 | -1.35% |
| Cholesterol
500 mg/dL | Li Hep | 52.68 | 53.69 | 1.94% |
| Cholesterol
500 mg/dL | Serum | 53.12 | 53.58 | 0.87% |
| Hemoglobin
500 mg/dL | Li Hep | 62.08 | 60.16 | -3.09% |
| Hemoglobin
500 mg/dL | Serum | 62.37 | 59.69 | -4.31% |
| Protein (Albumin)
6 g/dL | Li Hep | 58.95 | 59.35 | 0.68% |
| Protein (Albumin)
6 g/dL | Serum | 60.49 | 60.04 | -0.74% |
| Protein (Gamma Globulin)
2.5 g/dL | Li Hep | 56.08 | 55.07 | -1.81% |
| Protein (Gamma Globulin)
2.5 g/dL | Serum | 55.82 | 55.96 | 0.26% |
| Protein (Total)
12 g/dL | Li Hep | 57.12 | 59.14 | 3.53% |
| Protein (Total)
12 g/dL | Serum | 58.25 | 57.77 | -0.82% |
| Triglycerides
2000 mg/dL | Li Hep | 55.51 | 54.92 | -1.07% |
| Triglycerides
2000 mg/dL | Serum | 53.02 | 54.53 | 2.86% |
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 ADVIA Centaur TNIH assay in terms of the clinical concordance between the 99th 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 ADVIA Centaur TNIH assay in terms of its correlation to the the diagnosis of AMI.
Results were analyzed according to time from presentation to the emergency department.
| Matrix | Timepoint | N | Estimate | 95% CI | N | Estimate | 95% CI | N | Estimate | 95% CI | N | Estimate | 95% CI |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Li Hep | |||||||||||||
| Plasma | 0-1.5hr | 41 | 82.9% | 68.7-91.5 | 396 | 93.9% | 91.1-95.9 | 58 | 58.6% | 45.8-70.4 | 379 | 98.2% | 96.2-99.1 |
| ≥1.5-2.5 hr | 76 | 89.5% | 80.6-94.6 | 710 | 91.8% | 89.6-93.6 | 126 | 54.0% | 45.3-62.4 | 660 | 98.8% | 97.6-99.4 | |
| ≥2.5-3.5 hr | 72 | 95.8% | 88.5-98.6 | 605 | 91.9% | 89.5-93.8 | 118 | 58.5% | 49.5-67.0 | 559 | 99.5% | 98.4-99.8 | |
| ≥3.5-4.5 hr | 52 | 94.2% | 84.4-98.0 | 481 | 89.4% | 86.3-91.8 | 100 | 49.0% | 39.4-58.7 | 433 | 99.3% | 98.0-99.8 | |
| ≥4.5-6 hr | 24 | 95.8% | 79.8-99.3 | 239 | 86.2% | 81.2-90.0 | 56 | 41.1% | 29.2-54.1 | 207 | 99.5% | 97.3-99.9 | |
| ≥6-9 hr | 70 | 95.7% | 88.1-98.5 | 370 | 87.8% | 84.1-90.8 | 112 | 59.8% | 50.6-68.4 | 328 | 99.1% | 97.3-99.7 | |
| ≥9-24 hr | 71 | 94.4% | 86.4-97.8 | 347 | 88.8% | 85.0-91.7 | 106 | 63.2% | 53.7-71.8 | 312 | 98.7% | 96.8-99.5 | |
| ≥24 hr | 25 | 100.0% | 86.7-100 | 106 | 82.1% | 73.7-88.2 | 44 | 56.8% | 42.2-70.3 | 87 | 100.0% | 95.8-100 | |
| Serum | 0-1.5hr | 41 | 80.5% | 66.0-89.8 | 405 | 94.8% | 92.2-96.6 | 54 | 61.1% | 47.8-73.0 | 392 | 98.0% | 96.0-99.0 |
| ≥1.5-2.5 hr | 77 | 88.3% | 79.3-93.7 | 708 | 91.9% | 89.7-93.7 | 125 | 54.4% | 45.7-62.9 | 660 | 98.6% | 97.4-99.3 | |
| ≥2.5-3.5 hr | 67 | 95.5% | 87.6-98.5 | 615 | 92.8% | 90.5-94.6 | 108 | 59.3% | 49.8-68.1 | 574 | 99.5% | 98.5-99.8 | |
| ≥3.5-4.5 hr | 47 | 93.6% | 82.8-97.8 | 484 | 90.3% | 87.3-92.6 | 91 | 48.4% | 38.4-58.5 | 440 | 99.3% | 98.0-99.8 | |
| ≥4.5-6 hr | 24 | 95.8% | 79.8-99.3 | 239 | 87.0% | 82.2-90.7 | 54 | 42.6% | 30.3-55.8 | 209 | 99.5% | 97.3-99.9 | |
| ≥6-9 hr | 68 | 95.6% | 87.8-98.5 | 379 | 88.7% | 85.1-91.5 | 108 | 60.2% | 50.8-68.9 | 339 | 99.1% | 97.4-99.7 | |
| ≥9-24 hr | 71 | 94.4% | 86.4-97.8 | 353 | 89.8% | 86.2-92.5 | 103 | 65.0% | 55.5-73.6 | 321 | 98.8% | 96.8-99.5 | |
| ≥24 hr | 28 | 96.4% | 82.3-99.4 | 107 | 84.1% | 76.0-89.8 | 44 | 61.4% | 46.6-74.3 | 91 | 98.9% | 94.0-99.8 |
Using the female-specific 99th percentiles for lithium heparin plasma (36.99 pg/mL) and serum (39.59 pg/mL), the following results were obtained.
12
510(k) Summary of Safety and Effectiveness
Using the male-specific 99" percentiles for lithium heparin plasma (57.27 pg/mL) and serum
(58.05 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 | 74.0% | 64.6-81.6 | 561 | 92.0% | 89.4-94.0 | 119 | 62.2% | 53.2-70.4 | 542 | 95.2% | 93.1-96.7 | |
| ≥1.5-2.5 hr | 162 | 87.7% | 81.7-91.9 | 913 | 90.7% | 88.6-92.4 | 227 | 62.6% | 56.1-68.6 | 848 | 97.6% | 96.4-98.5 | ||
| ≥2.5-3.5 hr | 126 | 89.7% | 83.1-93.9 | 740 | 90.1% | 87.8-92.1 | 186 | 60.8% | 53.6-67.5 | 680 | 98.1% | 96.8-98.9 | ||
| ≥3.5-4.5 hr | 97 | 86.6% | 78.4-92.0 | 597 | 92.5% | 90.1-94.3 | 129 | 65.1% | 56.6-72.8 | 565 | 97.7% | 96.1-98.7 | ||
| ≥4.5-6 hr | 39 | 92.3% | 79.7-97.3 | 218 | 92.2% | 87.9-95.1 | 53 | 67.9% | 54.5-78.9 | 204 | 98.5% | 95.8-99.5 | ||
| ≥6-9 hr | 124 | 87.9% | 81.0-92.5 | 520 | 88.8% | 85.9-91.3 | 167 | 65.3% | 57.8-72.1 | 477 | 96.9% | 94.9-98.1 | ||
| ≥9-24 hr | 141 | 91.5% | 85.7-95.1 | 491 | 84.7% | 81.3-87.6 | 204 | 63.2% | 56.4-69.6 | 428 | 97.2% | 95.2-98.4 | ||
| ≥24 hr | 37 | 86.5% | 72.0-94.1 | 140 | 89.3% | 83.1-93.4 | 47 | 68.1% | 53.8-79.6 | 130 | 96.2% | 91.3-98.3 | ||
| Serum | 0-1.5hr | 101 | 75.2% | 66.0-82.6 | 573 | 92.8% | 90.4-94.7 | 117 | 65.0% | 56.0-73.0 | 557 | 95.5% | 93.5-96.9 | |
| ≥1.5-2.5 hr | 159 | 85.5% | 79.2-90.2 | 922 | 91.5% | 89.6-93.2 | 214 | 63.6% | 56.9-69.7 | 867 | 97.3% | 96.1-98.2 | ||
| ≥2.5-3.5 hr | 123 | 86.2% | 79.0-91.2 | 756 | 91.1% | 88.9-93.0 | 173 | 61.3% | 53.8-68.2 | 706 | 97.6% | 96.2-98.5 | ||
| ≥3.5-4.5 hr | 98 | 84.7% | 76.3-90.5 | 605 | 93.1% | 90.7-94.8 | 125 | 66.4% | 57.7-74.1 | 578 | 97.4% | 95.8-98.4 | ||
| ≥4.5-6 hr | 38 | 94.7% | 82.7-98.5 | 220 | 90.9% | 86.4-94.0 | 56 | 64.3% | 51.2-75.5 | 202 | 99.0% | 96.5-99.7 | ||
| ≥6-9 hr | 122 | 87.7% | 80.7-92.4 | 526 | 90.5% | 87.7-92.7 | 157 | 68.2% | 60.5-74.9 | 491 | 96.9% | 95.0-98.1 | ||
| ≥9-24 hr | 143 | 91.6% | 85.9-95.1 | 496 | 86.1% | 82.8-88.9 | 200 | 65.5% | 58.7-71.7 | 439 | 97.3% | 95.3-98.4 | ||
| ≥24 hr | 37 | 89.2% | 75.3-95.7 | 148 | 89.9% | 84.0-93.8 | 48 | 68.8% | 54.7-80.1 | 137 | 97.1% | 92.7-98.9 |
Using the overall 99th Percentile (47.34 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 | 141 | 78.0% | 70.5-84.1 | 957 | 92.8% | 91.0-94.3 | 179 | 61.5% | 54.2-68.3 | 919 | 96.6% | 95.3-97.6 | |||
| ≥1.5-2.5 hr | 238 | 89.5% | 85.0-92.8 | 1623 | 90.7% | 89.2-92.0 | 364 | 58.5% | 53.4-63.5 | 1497 | 98.3% | 97.5-98.9 | ||||
| ≥2.5-3.5 hr | 198 | 92.9% | 88.5-95.7 | 1345 | 90.4% | 88.7-91.9 | 313 | 58.8% | 53.3-64.1 | 1230 | 98.9% | 98.1-99.3 | ||||
| ≥3.5-4.5 hr | 149 | 91.3% | 85.6-94.8 | 1078 | 90.9% | 89.0-92.5 | 234 | 58.1% | 51.7-64.3 | 993 | 98.7% | 97.8-99.2 | ||||
| ≥4.5-6 hr | 63 | 95.2% | 86.9-98.4 | 457 | 89.5% | 86.3-92.0 | 108 | 55.6% | 46.2-64.6 | 412 | 99.3% | 97.9-99.8 | ||||
| ≥6-9 hr | 194 | 92.8% | 88.3-95.7 | 890 | 88.1% | 85.8-90.1 | 286 | 62.9% | 57.2-68.3 | 798 | 98.2% | 97.1-99.0 | ||||
| ≥9-24 hr | 212 | 92.9% | 88.7-95.7 | 838 | 85.9% | 83.4-88.1 | 315 | 62.5% | 57.1-67.7 | 735 | 98.0% | 96.7-98.8 | ||||
| ≥24 hr | 62 | 93.5% | 84.6-97.5 | 246 | 86.2% | 81.3-89.9 | 92 | 63.0% | 52.8-72.2 | 216 | 98.1% | 95.3-99.3 | ||||
| Serum | 0-1.5hr | 142 | 78.9% | 71.4-84.8 | 978 | 93.1% | 91.4-94.6 | 179 | 62.6% | 55.3-69.3 | 941 | 96.8% | 95.5-97.8 | |||
| ≥1.5-2.5 hr | 236 | 88.6% | 83.9-92.0 | 1630 | 91.4% | 90.0-92.7 | 349 | 59.9% | 54.7-64.9 | 1517 | 98.2% | 97.4-98.8 | ||||
| ≥2.5-3.5 hr | 190 | 92.1% | 87.4-95.2 | 1371 | 91.2% | 89.6-92.6 | 296 | 59.1% | 53.4-64.6 | 1265 | 98.8% | 98.1-99.3 | ||||
| ≥3.5-4.5 hr | 145 | 90.3% | 84.4-94.2 | 1089 | 91.5% | 89.7-93.0 | 224 | 58.5% | 51.9-64.7 | 1010 | 98.6% | 97.7-99.2 | ||||
| ≥4.5-6 hr | 62 | 96.8% | 89.0-99.1 | 459 | 89.1% | 85.9-91.6 | 110 | 54.5% | 45.2-63.5 | 411 | 99.5% | 98.2-99.9 | ||||
| ≥6-9 hr | 190 | 91.6% | 86.8-94.8 | 905 | 88.5% | 86.3-90.4 | 278 | 62.6% | 56.8-68.1 | 817 | 98.0% | 96.8-98.8 | ||||
| ≥9-24 hr | 214 | 93.0% | 88.8-95.7 | 849 | 86.7% | 84.2-88.8 | 312 | 63.8% | 58.3-68.9 | 751 | 98.0% | 96.7-98.8 | ||||
| ≥24 hr | 65 | 92.3% | 83.2-96.7 | 255 | 86.3% | 81.5-90.0 | 95 | 63.2% | 53.1-72.2 | 225 | 97.8% | 94.9-99.0 |
13
10.14 Traceability and Value Assignment
The ADVIA Centaur 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 ADVIA Centaur 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 ADVIA Centaur TNIH Reagents is 28 days with a calibration interval of 28 days.
Conclusions 11.
The new ADVIA Centaur High-Sensitivity Troponin I (TNIH) assay (Reagents and Calibrators) is substantially equivalent in principle and performance to the currentlymarketed predicate device, the Elecsys Troponin T Gen 5 STAT Immunoassay, cleared under 510(k) K162895.