(625 days)
Not Found
No
The device description and performance studies focus on a standard immunoassay technology (CMIA) and statistical analysis of clinical data, with no mention of AI or ML algorithms being used for data processing, interpretation, or diagnosis.
No.
This device is an in vitro diagnostic (IVD) assay designed to aid in the diagnosis of myocardial infarction by measuring cardiac troponin I levels, not to directly treat a medical condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that "The Alinity i STAT High Sensitivity Troponin-I assay is to be used as an aid in the diagnosis of myocardial infarction (MI)." This clearly indicates its role in diagnosis.
No
The device description clearly outlines physical components (reagent kit with microparticles and conjugate) and a chemical process (chemiluminescent microparticle immunoassay) performed on a specific hardware system (Alinity i system). This is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is "used for the quantitative determination of cardiac troponin I (cTnI) in human plasma... on the Alinity i system" and is to be used "as an aid in the diagnosis of myocardial infarction (MI)." This clearly indicates that the device is intended for use in vitro (outside the body) to examine specimens (human plasma) to provide information for diagnostic purposes (aiding in the diagnosis of MI).
- Device Description: The description details a "chemiluminescent microparticle immunoassay (CMIA)" which is a laboratory technique performed on biological samples. It describes the reagents used and the process of analyzing the sample to determine the amount of cTnI.
- Performance Studies: The document describes both nonclinical and clinical studies performed on specimens (human plasma) to evaluate the performance of the assay. This is characteristic of IVD devices.
The definition of an In Vitro Diagnostic (IVD) device is a medical device that is intended for use in vitro for the examination of specimens, including blood and tissue samples, derived from the human body, solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to determine the compatibility of transfused blood, organs and tissues, or to monitor therapeutic measures. This device fits that definition.
N/A
Intended Use / Indications for Use
The Alinity i STAT High Sensitivity Troponin-I assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of cardiac troponin I (cTnI) in human plasma (lithium heparin) on the Alinity i system.
The Alinity i STAT High Sensitivity Troponin-I assay is to be used as an aid in the diagnosis of myocardial infarction (MI).
Product codes
MMI
Device Description
The Alinity i STAT High Sensitivity Troponin-I Reagent Kit contains:
- Microparticles: 1 bottle (6.6 mL per 100 test cartridge / 33.8 mL per 600 test cartridge). Anti-troponin I (mouse, monoclonal) coated microparticles in TRIS buffer with protein (bovine) stabilizer. Minimum concentration: 0.035% solids. Preservative: ProClin 300.
- Conjugate: 1 bottle (6.1 mL per 100 test cartridge / 33.8 mL per 600 test cartridge). Anti-troponin I (mouse-human chimeric, monoclonal) acridinium-labeled conjugate in MES buffer with protein (bovine) stabilizer and human IgG. Minimum concentration: 0.1 mg/L. Preservative: ProClin 300.
Principles of the Procedure
The Alinity i STAT High Sensitivity Troponin-I assay is an automated, two-step immunoassay for the quantitative determination of cTnI in human plasma (lithium heparin) using CMIA technology.
Sample and anti-troponin I antibody-coated paramagnetic microparticles are combined and incubated. The cTnI present in the sample binds to the anti-troponin I coated microparticles. The mixture is washed. Anti-troponin I acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added. The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of cTnI in the sample and the RLU detected by the system optics.
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
Prescription Use
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
A multi-center prospective study was performed to assess diagnostic accuracy of the Alinity i STAT High Sensitivity Troponin-I assay. Specimens were collected at 23 EDs from 6174 subjects presenting to the ED with chest discomfort or equivalent ischemic symptoms consistent with ACS. The specimen collection sites represented geographically diverse EDs associated with primary care hospitals and medical centers, reflecting regional, urban, and rural patient populations. All subject diagnoses were adjudicated by a panel of board-certified cardiologists based on the third universal definition of MI. The adjudicators were blinded to the Alinity i STAT High Sensitivity Troponin-I assay results.
The specimens were collected in lithium heparin or lithium heparin separator tubes. The specimens were evaluated using the Alinity i STAT High Sensitivity Troponin-I assay.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Nonclinical Performance: Precision, Lower Limits of Measurement, Linearity, Analytical Specificity (Interference, Cross-Reactants), Expected Values. Clinical Performance: aid in the diagnosis of MI.
Sample Size:
- Precision (Reproducibility): 12 replicates per sample in each concentration range. Samples: 17 different samples with concentrations from 3.5 ng/L to 2871.4 ng/L.
- Precision (Within-Laboratory Precision): 80 replicates for each control level (Low Control, Medium Control, Bio-Rad Level 2).
- Lower Limits of Measurement: n ≥ 60 replicates of zero-analyte samples for LoB, n ≥ 60 replicates of low-analyte level samples for LoD and LoQ.
- Linearity: Tested across the analytical measuring interval of 2.7 to 3600.0 ng/L (pg/mL).
- Analytical Specificity (Interference): Each substance tested at 2 levels of analyte (approximately 15 ng/L and 500 ng/L, or 15 ng/L and 200 ng/L for hemoglobin).
- Cross-Reactants: Samples with cTnI target concentrations of 2.7, 15, and 500 ng/L.
- Expected Values: 1531 apparently healthy individuals (763 female, 766 male).
- Clinical Study for MI diagnosis: 6174 subjects presenting to the ED with chest discomfort or equivalent ischemic symptoms consistent with ACS.
- 891 specimens with serial sampling from 432 MI subjects (124 female, 308 male)
- 8975 specimens with serial sampling from 5742 non-MI subjects (2128 female, 3614 male)
AUC:
- Female:
- 0 to 8.8 g/dL (up to -16.3% decrease), Fibrinogen (24.3% interference at 1000 mg/dL with 15 ng/L analyte), HAMA > 150 ng/mL (up to -11.0% decrease), and RF > 1200 IU/mL (up to -18.9% decrease).
- Cross-Reactants: Observed % cross-reactivity ≤ 1% for all evaluated cross-reactants (Actin, Cardiac troponin C, Cardiac troponin T, Creatine kinase-MB, Myoglobin, Myosin, Skeletal troponin I, Tropomyosin).
- Expected Values (99th Percentile): Female: 14 ng/L, Male: 35 ng/L, Overall: 27 ng/L.
- Clinical Diagnostic Accuracy:
- Sex-specific cutoffs:
- Female (14 ng/L): Sensitivity ranged from 85.29% (0 to
- Sex-specific cutoffs:
§ 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 shows 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.
May 19, 2022
Abbott Laboratories Diagnostic Division Judi Wallach Regulatory Affairs Project Manager Dept. 09AA, Bldg. Ap8, 100 Abbott Park Road Abbott Park, Illinois 60064-6038
Re: K202525
Trade/Device Name: Alinity i STAT High Sensitivity Troponin-I Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine Phosphokinase/Creatine Kinase Or Isoenzymes Test System Regulatory Class: Class II Product Code: MMI Dated: February 1, 2022 Received: February 2, 2022
Dear Judi Wallach:
We have reviewed vour 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.
1
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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
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/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K202525
Device Name
Alinity i STAT High Sensitivity Troponin-I
Indications for Use (Describe)
The Alinity i STAT High Sensitivity Troponin-I assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of cardiac troponin I (cTnI) in human plasma (lithium heparin) on the Alinity i system.
The Alinity i STAT High Sensitivity Troponin-I assay is to be used as an aid in the diagnosis of myocardial infarction (MI).
| 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) |
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 5: 510(k) Summary
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Federal Food, Drug, and Cosmetic Act and 21 CFR 807.92.
I. 510(k) Number
II. Applicant Name
Date summary prepared: May 13, 2022
Abbott Laboratories Diagnostics Division Dept. 9AA, CP01-2 100 Abbott Park Road Abbott Park, IL 60064
Primary contact person for all communications:
Judi Wallach, ADD, Regulatory Affairs Project Manager Telephone Number: (224) 667-1132 Fax Number: (224) 667-4836
Secondary contact person for all communications:
Julian Braz, ADD, Director, Regulatory Affairs Telephone Number: (224) 330-9230
III. Device Name
Alinity i STAT High Sensitivity Troponin-I
Reagents
Trade Name: Alinity i STAT High Sensitivity Troponin-I Device Classification: Class II Classification Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Governing Regulation: 862.1215
Code: MMI
4
IV. Predicate Device
ARCHITECT STAT High Sensitivity Troponin-I (K191595)
V. Intended Use of the Device
The Alinity i STAT High Sensitivity Troponin-I assay is a chemiluminescent microparticle immunoassay (CMIA) used for the quantitative determination of cardiac troponin I (cTnI) in human plasma (lithium heparin) on the Alinity i system.
The Alinity i STAT High Sensitivity Troponin-I assay is to be used as an aid in the diagnosis of myocardial infarction (MI).
VI. Description of Device
The Alinity i STAT High Sensitivity Troponin-I Reagent Kit contains:
- . Microparticles: 1 bottle (6.6 mL per 100 test cartridge / 33.8 mL per 600 test cartridge). Anti-troponin I (mouse, monoclonal) coated microparticles in TRIS buffer with protein (bovine) stabilizer. Minimum concentration: 0.035% solids. Preservative: ProClin 300.
- . Conjugate: 1 bottle (6.1 mL per 100 test cartridge / 33.8 mL per 600 test cartridge). Anti-troponin I (mouse-human chimeric, monoclonal) acridinium-labeled conjugate in MES buffer with protein (bovine) stabilizer and human IgG. Minimum concentration: 0.1 mg/L. Preservative: ProClin 300.
Principles of the Procedure
The Alinity i STAT High Sensitivity Troponin-I assay is an automated, two-step immunoassay for the quantitative determination of cTnI in human plasma (lithium heparin) using CMIA technology.
Sample and anti-troponin I antibody-coated paramagnetic microparticles are combined and incubated. The cTnI present in the sample binds to the anti-troponin I coated microparticles. The mixture is washed. Anti-troponin I acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added.
5
The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of cTnI in the sample and the RLU detected by the system optics.
VII. Comparison of Technological Characteristics
The Alinity i STAT High Sensitivity Troponin-I assay (subject device) utilizes a CMIA methodology for the quantitative in vitro determination of cTnI and is intended for use on the Alinity i system.
The similarities and differences between the subject device and the predicate device are presented in the following table.
| Subject Device | Predicate Device | |
|---|---|---|
| Description | Alinity i STAT High Sensitivity | |
| Troponin-I | ARCHITECT STAT High Sensitivity | |
| Troponin-I (K191595) | ||
| General Device Characteristic Similarities | ||
| Intended Use / | ||
| Indications for Use | The Alinity i STAT High Sensitivity | |
| Troponin-I assay is a CMIA used for the | ||
| quantitative determination of cTnI in | ||
| human plasma (lithium heparin) on the | ||
| Alinity i system. | ||
| The Alinity i STAT High Sensitivity | ||
| Troponin-I assay is to be used as an aid in | ||
| the diagnosis of MI. | The ARCHITECT STAT High | |
| Sensitivity Troponin-I assay is a CMIA | ||
| used for the quantitative determination | ||
| of cTnI in human plasma (dipotassium | ||
| [K2] EDTA) on the ARCHITECT | ||
| 2000SR System. | ||
| The ARCHITECT STAT High | ||
| Sensitivity Troponin-I assay is to be | ||
| used as an aid in the diagnosis of MI. | ||
| Specific Analyte | ||
| Detected | cTnI | Same |
| General Device Characteristic Differences | ||
| Specimen Type | Plasma (lithium heparin) | Plasma (dipotassium EDTA) |
| 99th Percentile | ||
| Cutoff / Expected | ||
| Values from | ||
| Apparently Healthy | ||
| Individuals | ||
| (ng/L, pg/mL) | Female: 14 | |
| Male: 35 | ||
| Overall: 27 | Female: 17 | |
| Male: 35 | ||
| Overall: 28 |
6
VIII. Performance Summary*
A. Nonclinical
1. Precision
Reproducibility
A study was performed using 1 lot of the Alinity i STAT High Sensitivity Troponin-I reagents, 1 lot of the Alinity i STAT High Sensitivity Troponin-I Calibrators, and 1 lot of the Alinity i STAT High Sensitivity Troponin-I Controls. The study was performed to include lithium heparin separator plasma specimens within each of 5 target concentration ranges (> 3 to 6 ng/L, 10 to 20 ng/L, 30 to 50 ng/L, 100 to 300 ng/L, and 1000 ng/L to near the upper limit of the analytical measuring interval [AMI]). Only one specimen per concentration range was collected in a single day. The study was performed over a minimum of 3 days. Each specimen was stored at room temperature and tested in duplicate, twice in one day, on each of 3 instruments (for a total of 12 replicates) within 8 hours of collection.
| Sample | n | Mean
(ng/L, pg/mL) | Within-Run
SD | Within-Run
%CV | Between-Run
SD | Between-Run
%CV | Within-
Laboratorya
SD | Within-
Laboratorya
%CV | Reproducibilityb
SD | Reproducibilityb
%CV |
|--------|----|-----------------------|------------------|-------------------|-------------------|--------------------|------------------------------|-------------------------------|------------------------|-------------------------|
| 1 | 12 | 3.5 | 0.22 | 6.2 | 0.00 | 0.0 | 0.22 | 6.2 | 0.30 | 8.7 |
| 2 | 12 | 5.2 | 0.30 | 5.7 | 0.00 | 0.0 | 0.30 | 5.7 | 0.67 | 12.7 |
| 3 | 12 | 8.0 | 0.25 | 3.2 | 0.23 | 2.9 | 0.34 | 4.3 | 0.67 | 8.4 |
| 4 | 12 | 13.6 | 0.37 | 2.7 | 0.00 | 0.0 | 0.37 | 2.7 | 0.61 | 4.5 |
| 5 | 12 | 13.9 | 0.37 | 2.7 | 0.00 | 0.0 | 0.37 | 2.7 | 0.37 | 2.7 |
| 6 | 12 | 15.1 | 0.65 | 4.3 | 0.00 | 0.0 | 0.65 | 4.3 | 0.65 | 4.3 |
| 7 | 12 | 18.2 | 0.82 | 4.5 | 0.00 | 0.0 | 0.82 | 4.5 | 0.82 | 4.5 |
| 8 | 12 | 20.2 | 0.66 | 3.3 | 0.00 | 0.0 | 0.66 | 3.3 | 0.74 | 3.7 |
| 9 | 12 | 36.9 | 0.73 | 2.0 | 0.00 | 0.0 | 0.73 | 2.0 | 1.17 | 3.2 |
| 10 | 12 | 46.7 | 0.90 | 1.9 | 0.00 | 0.0 | 0.90 | 1.9 | 0.95 | 2.0 |
| 11 | 12 | 51.6 | 1.22 | 2.4 | 1.07 | 2.1 | 1.63 | 3.2 | 1.63 | 3.2 |
| 12 | 12 | 172.6 | 4.51 | 2.6 | 5.53 | 3.2 | 7.14 | 4.1 | 7.14 | 4.1 |
| 13 | 12 | 233.0 | 5.00 | 2.1 | 9.18 | 3.9 | 10.45 | 4.5 | 10.45 | 4.5 |
- Unless otherwise specified, all studies were performed on the Alinity i system.
7
| Sample | n | Mean
(ng/L,
pg/mL) | Within-Run | | Between-Run | | Within-
Laboratorya | | Reproducibilityb | |
|--------|----|--------------------------|------------|-----|-------------|-----|------------------------|-----|------------------|-----|
| 14 | 12 | 300.0 | 11.00 | 3.7 | 5.61 | 1.9 | 12.35 | 4.1 | 12.35 | 4.1 |
| 15 | 12 | 1228.3 | 29.03 | 2.4 | 45.23 | 3.7 | 53.74 | 4.4 | 53.74 | 4.4 |
| 16 | 12 | 1974.6 | 49.46 | 2.5 | 57.97 | 2.9 | 76.21 | 3.9 | 76.21 | 3.9 |
| 17 | 12 | 2871.4 | 72.86 | 2.5 | 85.31 | 3.0 | 112.19 | 3.9 | 112.19 | 3.9 |
ª Includes within-run and between-run variability.
b Includes within-run, between-run, and between-instrument variability.
Within-Laboratory Precision
A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Alinity i STAT High Sensitivity Troponin-I reagents, 2 lots of the Alinity i STAT High Sensitivity Troponin-I Calibrators, 1 lot of the Alinity i STAT High Sensitivity Troponin-I Controls, 1 lot of Bio-Rad Liquichek Cardiac Markers Plus Control LT (Level 2), and 2 instruments. Three controls were tested in duplicate, twice per day on 20 days (following the manufacturers' storage and handling requirements) on 6 reagent lot/calibrator lot/instrument combinations. The performance from a representative combination is shown in the following table.
Note: Patient samples can only be stored for 8 hours at room temperature; therefore, 20-day precision was conducted with quality controls.
| | | | | Within-Run
(Repeatability) | | Within-Laboratorya | |
|-----------------|----|-----------------------|-------|-------------------------------|------------------------|--------------------|--|
| Sample | n | Mean
(ng/L, pg/mL) | SD | %CV | SD
(Rangeb) | %CV
(Rangeb) | |
| Low Control | 80 | 19.9 | 0.73 | 3.7 | 0.81
(0.76-1.13) | 4.1
(3.9-5.1) | |
| Medium Control | 80 | 199.8 | 6.14 | 3.1 | 7.25
(5.54-7.25) | 3.6
(2.8-3.6) | |
| Bio-Rad Level 2 | 80 | 1442.7 | 45.91 | 3.2 | 60.02
(49.50-69.39) | 4.2
(3.3-4.5) | |
ª Includes within-run, between-run, and between-day variability.
- Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures: Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
8
2. Lower Limits of Measurement
A study was performed based on guidance from CLSI EP17-A2. * Testing was conducted using 2 lots of the Alinity i STAT High Sensitivity Troponin-I reagents on each of 2 instruments (1 instrument for limit of blank [LoB]). The maximum observed LoB, limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below. These representative data support the lower limit of the analytical measuring interval.
| ng/L (pg/mL) | |
|---|---|
| LoBa | 0.0 |
| LoDb | 0.9 |
| LoQc | 2.7 |
a The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.
b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.
C The LoQ is defined as the lowest concentration at which a maximum allowable precision of 20 %CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.
3. Linearitv
A study was performed based on guidance from CLSI EP06-A. This assay is linear across the analytical measuring interval of 2.7 to 3600.0 ng/L (pg/mL).
" Clinical and Laboratory Standards Institute (CLSI). Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.
- Clinical and Laboratory Standards Institute (CLSI). Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline. CLSI Document EP06-A. Wayne, PA: CLSI; 2003.
9
4. Analytical Specificity
a. Interference
Potentially Interfering Endogenous Substances
A study was performed based on guidance from CLSI EP07, 3rd ed. * Each substance was tested at 2 levels of the analyte (approximately 15 ng/L and 500 ng/L for bilirubin, total protein, and Intralipid and 15 ng/L and 200 ng/L for hemoglobin).
No significant interference (interference within ± 10%) was observed at the following concentrations.
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Bilirubin (conjugated) | 40 mg/dL |
| Bilirubin (unconjugated) | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Total protein | 8.8 g/dL |
| Intralipid | 3000 mg/dL |
Interference beyond ± 10% was observed at the concentration shown below for the following substance.
| Potentially Interfering
Substance | Interferent
Level | Analyte
Level | % Interference |
|--------------------------------------|----------------------|------------------|----------------|
| Total Protein | 9.0 g/dL | 500 ng/L | -10.9% |
The Alinity i STAT High Sensitivity Troponin-I assay is susceptible to interference effects from total protein > 8.8 g/dL. Total protein from 9.0 to 12.0 g/dL decreased troponin values at 500 ng/L by up to -16.3%.
- Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
10
Potentially Interfering Drugs
A study was performed based on guidance from CLSI EP07-A2* and EP07, 3rd ed. Each drug was tested at 2 levels of the analyte (approximately 15 ng/L and 500 ng/L).
No significant interference (interference within ± 10%) was observed at the following concentrations.
| Potentially Interfering
Drug | Interferent
Level | Potentially Interfering
Drug | Interferent
Level |
|---------------------------------|----------------------|---------------------------------|----------------------|
| Acetaminophen | 250 µg/mL | Ibuprofen | 500 µg/mL |
| Acetylsalicylic Acid | 1000 µg/mL | Levodopa | 20 µg/mL |
| Adrenaline | 0.37 µg/mL | Low MW Heparin | 5 U/mL |
| Allopurinol | 400 µg/mL | Methyldopa | 25 µg/mL |
| Ambroxol | 400 µg/mL | Methylprednisolone | 80 µg/mL |
| Ampicillin | 1000 µg/mL | Metronidazole | 200 µg/mL |
| Ascorbic Acid | 300 µg/mL | Nicotine | 2 mg/dL |
| Atenolol | 10 µg/mL | Nifedipine | 60 µg/mL |
| Biotin | 4250 ng/mL | Nitrofurantoin | 64 µg/mL |
| Bivalirudin | 42 µg/mL | Nystatin | 7.5 µg/mL |
| Caffeine | 100 µg/mL | Oxytetracycline | 5 µg/mL |
| Captopril | 50 µg/mL | Phenylbutazone | 400 µg/mL |
| Carvedilol | 150 µg/mL | Phenytoin | 100 µg/mL |
| Cefoxitin | 2500 µg/mL | Primidone | 10 mg/dL |
| Cinnarizine | 400 µg/mL | Propranolol | 5 µg/mL |
| Clopidogrel | 75 µg/mL | Quinidine | 20 µg/mL |
| Cocaine | 10 µg/mL | Rifampicin | 60 µg/mL |
| Cyclosporine | 5 µg/mL | Salicylic Acid | 600 µg/mL |
| Diclofenac | 50 µg/mL | Simvastatin | 20 µg/mL |
| Digoxin | 7.5 µg/mL | Sodium Heparin | 8 U/mL |
| Dopamine | 900 µg/mL | Streptokinase | 31.3 U/mL |
| Doxycycline | 50 µg/mL | Theophylline | 75 µg/mL |
| Entifibatide | 7 µg/mL | TPA | 2.3 µg/mL |
- Clinical and Laboratory Standards Institute (CLS). Interference Testing in Clinical Chemistry; Approved Guideline-Second Edition. CLSI Document EP07-A2. Wayne, PA: CLSI; 2005.
11
| Potentially Interfering
Drug | Interferent
Level | Potentially Interfering
Drug | Interferent
Level |
|---------------------------------|----------------------|---------------------------------|----------------------|
| Erythromycin | 200 µg/mL | Trimethoprim | 75 µg/mL |
| Fondaparinux | 4 µg/mL | Verapamil | 160 µg/mL |
| Furosemide | 400 µg/mL | Warfarin | 30 µg/mL |
MW = Molecular weight
TPA = Tissue plasminogen activator
Interference beyond ± 10% was observed at the concentration shown
below for the following drug.
| Potentially Interfering
Drug | Interferent
Level | Analyte
Level | % Interference |
|---------------------------------|----------------------|------------------|----------------|
| Fibrinogen | 1000 mg/dL | 15 ng/L | 24.3% |
Specimens from individuals with elevated levels of fibrinogen may demonstrate falsely elevated values.
Potentially Interfering Other Conditions
Specimens containing human anti-mouse antibodies (HAMA) were evaluated at 3 levels of the analyte (approximately 2.7, 15, and 500 ng/L) with the Alinity i STAT High Sensitivity Troponin-I assay. The individual differences for samples near 2.7 ng/L ranged from -0.2 to 0.1 ng/L. The individual % differences for samples near 15 ng/L and 500 ng/L ranged from -8.9% to -0.5%. No significant interference (interference within ± 10%) was observed with specimens containing HAMA at concentrations up to 150 ng/mL.
The Alinity i STAT High Sensitivity Troponin-I assay is susceptible to interference effects from HAMA > 150 ng/mL. HAMA at 225 ng/mL decreased troponin values up to -11.0%.
Samples at 3 levels of the analyte (approximately 2.7, 15, and 500 ng/L) were spiked with rheumatoid factor (RF) to concentrations of 1200 IU/mL
12
and 1495 IU/mL and tested with the Alinity i STAT High Sensitivity Troponin-I assay. For samples tested at an RF concentration of 1200 IU/mL, the difference for a sample near 2.7 ng/L was 0.3 ng/L, and the % differences for samples near 15 ng/L and 500 ng/L were -7.1% and -7.6%, respectively. For samples tested at an RF concentration of 1495 IU/mL. the difference for a sample near 2.7 ng/L was -0.1 ng/L, and the % differences for samples near 15 ng/L and 500 ng/L were -12.6% and -18.9%, respectively.
The Alinity i STAT High Sensitivity Troponin-I assay is susceptible to interference effects from RF > 1200 IU/mL. RF at 1495 IU/mL decreased troponin values up to -18.9%.
Although the Alinity i STAT High Sensitivity Troponin-I assay is specifically designed to minimize the effects of HAMA, heterophilic antibodies, and RF, assay results may be impacted by these proteins.
Troponin autoantibodies have been reported to be present in approximately 10% to 20% of patients presenting to the emergency department (ED) and may lead to falsely low troponin assay results and delay in treatment of acute coronary syndrome (ACS). ** Therefore, a test result that is inconsistent with the clinical picture and patient history should be interpreted with caution.
Park JY, Jaffe AS. Troponin autoantibodies: from assay interferent to mediator of cardiotoxicity. Clin Chem 2017;63(1):30-32.
- Nussinovitch U, Shoenfeld Y. Anti-troponin autoantibodies and the cardiovascular system. Heart 2010;96:1518-1524.
13
b. Cross-Reactants
A study was performed based on guidance from CLSI EP07, 3rd ed. Samples with cTnI target concentrations of 2.7, 15, and 500 ng/L containing the cross-reactants at the concentrations listed below were tested with the Alinity i STAT High Sensitivity Troponin-I assay. The observed % cross-reactivity was ≤ 1% for all cross-reactants evaluated at each analyte level.
| Cross-Reactant | Cross-Reactant Concentration |
|---|---|
| Actin | 1 000 000 ng/L |
| Cardiac troponin C | 1 000 000 ng/L |
| Cardiac troponin T | 1 000 000 ng/L |
| Creatine kinase-MB (CK-MB) | 1 000 000 ng/L |
| Myoglobin | 1 000 000 ng/L |
| Myosin | 1 000 000 ng/L |
| Skeletal troponin I | 1 000 000 ng/L |
| Tropomyosin | 1 000 000 ng/L |
5. Expected Values
This study was performed on the ARCHITECT i2000SR System.
A reference range study was conducted based on guidance from CLSI EP28-A3c. Specimens were collected from 1531 apparently healthy individuals in a US population with normal levels of cardiac B-type natriuretic peptide (BNP) and HbA1c, and glomerular filtration rate (GFR) values ≥ 60 mL/min. Each specimen was stored frozen, thawed, and evaluated in replicates of one using the ARCHITECT STAT High Sensitivity Troponin-I assay. The 99th
- Clinical and Laboratory Standards Institute (CLSI). Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline-Third Edition. CLSI document EP28-A3c. Wayne, PA: CLSI; 2010.
14
| Apparently
Healthy Population | n | Age Range
(years) | 99th Percentile
(ng/L, pg/mL) | 90% CI
(ng/L, pg/mL) |
|----------------------------------|------|----------------------|----------------------------------|-------------------------|
| Female | 763a | 21 - 75 | 14 | [12, 17] |
| Male | 766 | 21 - 73 | 35 | [27, 44] |
| Overall | 1531 | 21 - 75 | 27 | [22, 32] |
percentiles described in the following table for this population were determined using the robust statistical method described in CLSI EP28-A3c.
ª During the sex-specific analysis. 2 female subjects were identified as outliers. The subjects and results were excluded from the sex-specific analysis but were included in the overall analysis.
B. Clinical
The Alinity i STAT High Sensitivity Troponin-I results should be used in conjunction with other diagnostic information such as electrocardiogram (ECG), clinical observations and information, and patient symptoms to aid in the diagnosis of MI.
A multi-center prospective study was performed to assess diagnostic accuracy of the Alinity i STAT High Sensitivity Troponin-I assay. Specimens were collected at 23 EDs from 6174 subjects presenting to the ED with chest discomfort or equivalent ischemic symptoms consistent with ACS. The specimen collection sites represented geographically diverse EDs associated with primary care hospitals and medical centers, reflecting regional, urban, and rural patient populations. All subject diagnoses were adjudicated by a panel of board-certified cardiologists based on the third universal definition of MI. The adjudicators were blinded to the Alinity i STAT High Sensitivity Troponin-I assay results. The observed MI prevalence in this study was 7.0%.
- . 891 specimens with serial sampling from 432 MI subjects (124 female subjects, 308 male subjects)
- . 8975 specimens with serial sampling from 5742 non-MI subjects (2128 female subjects, 3614 male subjects)
" Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J 2012;33(20):2551-2567.
15
The specimens were collected in lithium heparin or lithium heparin separator tubes. The specimens were evaluated using the Alinity i STAT High Sensitivity Troponin-I assay.
NOTE: The study population did not include type 4 or 5 MI subjects. Therefore, the ability of the assay to identify these patients was not evaluated.
The results were analyzed using the serial sampling time points collected as part of the ED visit.
An analysis for both females and males was performed using the sex-specific 99th percentile cutoffs (female 14 ng/L, male 35 ng/L). The results are summarized in the following table.
| Cutoff
(ng/L) | Time
Pointa | nb | Sensitivityc
% | 95% CI | Specificityd
% | 95% CI | PPVe
% | 95% CI | NPVf
% | 95% CI |
|------------------------|-------------------|------|--------------------|-------------|----------------------|-------------|--------------------|-------------|----------------------|-------------|
| 14
(Female
only) | 0 to cutpoint | A | B |
| cTnI Value ≤ cutpoint | C | D |
6 Sensitivity = A/(A + C) × 100%
d Specificity = D/(B + D) × 100%
€ Positive predictive value (PPV) = A/(A + B) × 100%
f Negative predictive value (NPV) = D/(C + D) × 100%
- 8 The study design followed the standard of care at each site where few specimens would be obtained at later time points because most patients would not typically require further serial cTnI testing after 6 hours. Therefore, the lower specificity at the ≥ 6 hour time point was the result of the disproportionate number of elevated and non-elevated specimens carried over from previous time points. The cTnI value should be used in conjunction with information available from clinical evaluation and other diagnostic procedures.
- h Of the specimens collected at greater than or equal to 6 hours, all were collected within 19 hours from presentation to the ED, except for one specimen from a male collected at 35 hours.
" Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021;144:e368-e454.
17
Prevalence of adjudicated MI in the study population was 7.0% (5.5% for females and 7.9% for males).
In the Alinity i STAT High Sensitivity Troponin-I clinical study, the percent of false negatives for females using the sex-specific cutoff (14 ng/L) was up to 2.41% lower when compared to the false negative rate for females when using the overall cutoff of 27 ng/L. When using the female cutoff of 14 ng/L, 5.65% of females with MI had non-elevated Alinity i STAT High Sensitivity Troponin-I test results. When using the overall cutoff of 27 ng/L, 8.06% of females with MI had non-elevated Alinity i STAT High Sensitivity Troponin-I test results. Troponin results should always be used in conjunction with clinical data, signs, and symptoms.
In the Alinity i STAT High Sensitivity Troponin-I clinical study, the percent of false negatives for males using the sex-specific cutoff (35 ng/L) was up to 1.63% higher when compared to the false negative rate for males when using the overall cutoff of 27 ng/L. When using the male cutoff of 35 ng/L, 8.12% of males with MI had non-elevated Alinity i STAT High Sensitivity Troponin-I test results. When using the overall cutoff of 27 ng/L, 6.49% of males with MI had non-elevated Alinity i STAT High Sensitivity Troponin-I test results. Troponin results should always be used in conjunction with clinical data, signs, and symptoms.
When using the female cutoff of 14 ng/L, the lower bound of the 95% CI for the PPV was as low as 21.45%. Taking into consideration the lower bound of the 95% CI, up to 77.54% (at 0 to " Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol 2018;72(18):2231-2264.
19
A sex difference in 99th percentile has been reported. **
In the clinical trial, 14.1% of patients without an MI diagnosis had at least one Alinity i STAT High Sensitivity Troponin-I test result above the sex-specific 99th percentile on one or more serial draws.
One or more of the following conditions were found in 94.2% of these patients:
| Cardiac Conditions | Non-Cardiac Conditions |
|---|---|
| Atrial fibrillation | Cerebrovascular accidents and subarachnoid bleeds |
| Cardiotoxic drugs | Chronic obstructive pulmonary disease |
| Heart failure | Chronic renal insufficiency with or without hemodialysis |
| Hypertension | Cocaine user |
| Infiltrative cardiomyopathies | Diabetes mellitus |
| Left ventricular hypertrophy | Pulmonary embolism |
| Myocarditis | Rhabdomyolysis |
| Recent cardiac intervention and/or surgery | Sepsis |
| Recent MI | Vigorous exercise |
The Area Under the Curve (AUC) results are summarized in the following table.
| Sex | Time Pointa | nb | AUC | Standard Error | 95% Wald CI |
|---|---|---|---|---|---|
| Female | 0 to * Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem 2012:58(11):1574-1581. |
് Obuchowski NA. Fundamentals of clinical research for radiologists: ROC analysis. Am J Roentgenol 2005;184(2):364-372.
20
| Sex | Time Pointa | nb | AUC | Standard Error | 95% Wald CI |
|---|---|---|---|---|---|
| 1 to |