Alinity i STAT High Sensitivity Troponin-I
Device Facts
| Record ID | K202525 |
|---|---|
| Device Name | Alinity i STAT High Sensitivity Troponin-I |
| Applicant | Abbott Laboratories Diagnostics Division |
| Product Code | MMI · Clinical Chemistry |
| Decision Date | May 19, 2022 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1215 |
| Device Class | Class 2 |
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).
Device Story
The Alinity i STAT High Sensitivity Troponin-I is an automated, two-step chemiluminescent microparticle immunoassay (CMIA) for quantitative determination of cardiac troponin I (cTnI) in lithium heparin plasma. The device uses paramagnetic microparticles coated with anti-troponin I antibodies to capture cTnI from patient samples; a secondary anti-troponin I acridinium-labeled conjugate is added to form a sandwich complex. Chemiluminescence is measured as relative light units (RLU), which are directly proportional to cTnI concentration. The assay is performed on the Alinity i system in a clinical laboratory setting by trained personnel. Results are used by physicians in conjunction with clinical evaluation, ECG, and patient history to diagnose myocardial infarction. The device provides high-sensitivity detection, aiding in the rapid assessment of patients with suspected acute coronary syndrome.
Clinical Evidence
Prospective multi-center study of 6,171 subjects presenting to EDs with chest discomfort or ischemic symptoms. Adjudicated by cardiologists per third universal definition of MI. Sensitivity and specificity evaluated at 0-1, 1-3, 3-6, and ≥6 hours using 27 ng/L (overall) and sex-specific (14 ng/L female, 35 ng/L male) cutoffs. Prevalence of MI was 7.0%. Results demonstrate diagnostic performance for MI aid.
Technological Characteristics
CMIA technology; mouse monoclonal anti-troponin I coated paramagnetic microparticles; acridinium-labeled mouse-human chimeric monoclonal anti-troponin I conjugate. Requires Alinity i system. Reportable range 2.7 to 3600.0 ng/L. Traceable to NIST SRM2921. Software-controlled automated processing.
Indications for Use
Indicated for use as an aid in the diagnosis of myocardial infarction (MI) in patients presenting to the emergency department with chest discomfort or equivalent ischemic symptoms consistent with acute coronary syndrome.
Regulatory Classification
Identification
A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.
Predicate Devices
- ARCHITECT STAT High Sensitivity Troponin-I (K191595)
Related Devices
- K041192 — ARCHITECT STAT TROPONIN-I IMMUNOASSAY · Fisher Diagnostics · Aug 12, 2004
- K191595 — ARCHITECT STAT High Sensitivity Troponin-I · Abbott Laboratories Diagnostics Division · Sep 13, 2019
- K230994 — Alinity i STAT High Sensitivity Troponin-I · Abbott Laboratories Diagnostics Division · May 4, 2023
Submission Summary (Full Text)
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FDA U.S. FOOD & DRUG ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K202525
B Applicant
Abbott Laboratories Diagnostic Division
C Proprietary and Established Names
Alinity i STAT High Sensitivity Troponin-I
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| MMI | Class II | 21 CFR 862.1215 - Creatine Phosphokinase/ Creatine Kinase Or Isoenzymes Test System | CH - Clinical Chemistry |
## II Submission/Device Overview:
A Purpose for Submission:
New Device
B Measurand:
Cardiac Troponin I (cTnI)
C Type of Test:
Quantitative Immunoassay
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) 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).
### C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
For in vitro diagnostic use
### D Special Instrument Requirements:
Alinity i System
## IV Device/System Characteristics:
### A Device Description:
The following are needed to conduct testing:
Alinity i STAT High Sensitivity Troponin-I Reagent Kit which 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.
The following are also required to conduct testing but are not provided with the kit:
- Alinity i STAT High Sensitivity Troponin-I assay file
- 04Z2101 Alinity i STAT High Sensitivity Troponin-I Calibrators
- 04Z2110 Alinity i STAT High Sensitivity Troponin-I Controls or other control material containing cTnI
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- Alinity Pre-Trigger Solution
- Alinity Trigger Solution
- Alinity i-series Concentrated Wash Buffer
- 09P1540 Alinity i Multi-Assay Manual Diluent
## B Principle of Operation:
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 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.
## V Substantial Equivalence Information:
### A Predicate Device Name(s):
ARCHITECT STAT High Sensitivity Troponin-I
### B Predicate 510(k) Number(s):
K191595
### C Comparison with Predicate(s):
| Device & Predicate Device(s): | K202525 | K191595 |
| --- | --- | --- |
| Device Trade Name | Alinity i STAT High Sensitivity Troponin-I | ARCHITECT STAT High Sensitivity Troponin-I |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | The assay is for the quantitative determination of cardiac troponin I used as an aid in the diagnosis of myocardial infarction. | Same |
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| General Device Characteristic Differences | | |
| --- | --- | --- |
| Specimen Type | Plasma (lithium heparin) | Plasma (dipotassium [K2] 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 |
VI Standards/Guidance Documents Referenced:
- Clinical and Laboratory Standards Institute (CLSI) EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition
- CLSI EP07, 3rd ed., Interference Testing in Clinical Chemistry
- CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-Second Edition
- CLSI EP28-A3c, Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline-Third Edition
- CLSI EP35, 1st ed., Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures
VII Performance Characteristics (if/when applicable):
A Analytical Performance:
1. Precision/Reproducibility:
A study was performed using 1 lot of the Alinity i STAT High Sensitivity Troponin-I reagent, 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 using fresh, native lithium heparin plasma specimens within each of 5 concentration ranges (> 3 to 6 ng/L, 10 to 20 ng/L, 30 to 50 ng/L, and 100 to 300 ng/L, and 1000 to 4500 ng/L). Testing for each sample was performed within the 8-hour stability claim for patient samples. 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 per sample) within 8 hours of collection. Within-laboratory precision includes within-run and between-run variability. Reproducibility includes within-run, between-run, and between-instrument variance components.
| Sample | n | Mean (ng/L) | Within-Run | | Between-Run | | Within-Laboratory | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 12 | 3.5 | 0.22 | 6.2 | 0.00 | 0.0 | 0.22 | 6.2 | 0.30 | 8.7 |
| Sample 2 | 12 | 5.2 | 0.30 | 5.7 | 0.00 | 0.0 | 0.30 | 5.7 | 0.67 | 12.7 |
| Sample 3 | 12 | 8.0 | 0.25 | 3.2 | 0.23 | 2.9 | 0.34 | 4.3 | 0.67 | 8.4 |
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| Sample | n | Mean (ng/L) | Within-Run | | Between-Run | | Within-Laboratory | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 4 | 12 | 13.6 | 0.37 | 2.7 | 0.00 | 0.0 | 0.37 | 2.7 | 0.61 | 4.5 |
| Sample 5 | 12 | 13.9 | 0.37 | 2.7 | 0.00 | 0.0 | 0.37 | 2.7 | 0.37 | 2.7 |
| Sample 6 | 12 | 15.1 | 0.65 | 4.3 | 0.00 | 0.0 | 0.65 | 4.3 | 0.65 | 4.3 |
| Sample 7 | 12 | 18.2 | 0.82 | 4.5 | 0.00 | 0.0 | 0.82 | 4.5 | 0.82 | 4.5 |
| Sample 8 | 12 | 20.2 | 0.66 | 3.3 | 0.00 | 0.0 | 0.66 | 3.3 | 0.74 | 3.7 |
| Sample 9 | 12 | 36.9 | 0.73 | 2.0 | 0.00 | 0.0 | 0.73 | 2.0 | 1.17 | 3.2 |
| Sample 10 | 12 | 46.7 | 0.90 | 1.9 | 0.00 | 0.0 | 0.90 | 1.9 | 0.95 | 2.0 |
| Sample 11 | 12 | 51.6 | 1.22 | 2.4 | 1.07 | 2.1 | 1.63 | 3.2 | 1.63 | 3.2 |
| Sample 12 | 12 | 172.6 | 4.51 | 2.6 | 5.53 | 3.2 | 7.14 | 4.1 | 7.14 | 4.1 |
| Sample 13 | 12 | 233.0 | 5.00 | 2.1 | 9.18 | 3.9 | 10.45 | 4.5 | 10.45 | 4.5 |
| Sample 14 | 12 | 300.0 | 11.00 | 3.7 | 5.61 | 1.9 | 12.35 | 4.1 | 12.35 | 4.1 |
| Sample 15 | 12 | 1228.3 | 29.03 | 2.4 | 45.23 | 3.7 | 53.74 | 4.4 | 53.74 | 4.4 |
| Sample 16 | 12 | 1974.6 | 49.46 | 2.5 | 57.97 | 2.9 | 76.21 | 3.9 | 76.21 | 3.9 |
| Sample 17 | 12 | 2871.4 | 72.86 | 2.5 | 85.31 | 3.0 | 112.19 | 3.9 | 112.19 | 3.9 |
A second study was performed following the recommendations in the EP05-A3 guideline. Testing was conducted using 3 lots of the Alinity i STAT High Sensitivity Troponin-I reagent, 2 lots of the Alinity i STAT High Sensitivity Troponin-I Calibrators, and 1 lot of the Alinity i STAT High Sensitivity Troponin-I Controls using 2 instruments. Three controls were tested in duplicate, twice per day over 20 days. Within-laboratory variability contains within-run, between-run, and between-day variability. Patient samples can only be stored for 8 hours at room temperature; therefore, 20-day precision studies were conducted with quality control materials.
| Sample | Instrument | Reagent Lot | N | Mean (ng/L) | Within-Run | | Within-Laboratory (Total) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | SD | %CV | SD | %CV |
| Low Control | 1 | 1 | 80 | 20.1 | 0.59 | 2.9 | 0.87 | 4.3 |
| | | 2 | 80 | 20.0 | 0.61 | 3.0 | 0.91 | 4.5 |
| | | 3 | 80 | 22.0 | 0.72 | 3.3 | 1.13 | 5.1 |
| | 2 | 1 | 80 | 19.6 | 0.67 | 3.4 | 0.76 | 3.9 |
| | | 2 | 80 | 19.9 | 0.73 | 3.7 | 0.81 | 4.1 |
| | | 3 | 80 | 18.3 | 0.67 | 3.7 | 0.77 | 4.2 |
| Medium Control | 1 | 1 | 80 | 195.2 | 4.55 | 2.3 | 5.54 | 2.8 |
| | | 2 | 80 | 194.7 | 4.18 | 2.1 | 6.60 | 3.4 |
| | | 3 | 80 | 210.3 | 4.82 | 2.3 | 7.00 | 3.3 |
| | 2 | 1 | 80 | 191.9 | 4.42 | 2.3 | 6.72 | 3.5 |
| | | 2 | 80 | 199.8 | 6.14 | 3.1 | 7.25 | 3.6 |
| | | 3 | 80 | 191.9 | 5.22 | 2.7 | 6.05 | 3.2 |
| Commercial Control | 1 | 1 | 80 | 1484.6 | 41.19 | 2.8 | 49.50 | 3.3 |
| | | 2 | 80 | 1392.9 | 45.11 | 3.2 | 61.56 | 4.4 |
| | | 3 | 80 | 1624.9 | 40.02 | 2.5 | 63.56 | 3.9 |
| | 2 | 1 | 80 | 1475.4 | 36.28 | 2.5 | 63.39 | 4.3 |
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| Sample | Instrument | Reagent Lot | N | Mean (ng/L) | Within-Run | | Within-Laboratory (Total) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | SD | %CV | SD | %CV |
| | | 2 | 80 | 1442.7 | 45.91 | 3.2 | 60.02 | 4.2 |
| | | 3 | 80 | 1542.3 | 53.36 | 3.5 | 69.39 | 4.5 |
Reproducibility analysis was performed using single reagent lots of the Alinity i STAT High Sensitivity Troponin-I reagent, the Alinity i STAT High Sensitivity Troponin-I Calibrators, and the Alinity i STAT High Sensitivity Troponin-I Controls at three sites using 4 replicates per run, 2 runs per day, for 5 days at each site. Below are the between-site and reproducibility precision estimates for the three control materials. Reproducibility includes within-run, between-run, between-day, and between-site variance components.
| Sample | N | Mean (ng/L) | Between-Site | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV |
| Low Control | 480 | 20 | 1.34 | 7.2 | 1.55 | 8.3 |
| Medium Control | 480 | 197.3 | 5.69 | 2.9 | 7.65 | 3.9 |
| Commercial Control | 480 | 1493.8 | 42.18 | 2.7 | 80.58 | 5.2 |
2. Linearity:
Linearity was evaluated using 10 lithium heparin plasma samples ranging in concentrations from $<2.7 \, \mathrm{pg/mL}$ to $>3,600 \, \mathrm{ng/L}$ . The high samples and the low samples were native and the intermediate samples were prepared by mixing high and low concentration samples. At least four replicates were measured for each sample, and the mean of these replicates was used to calculate the reported results. Deviations from linearity within the claimed range were never observed to be greater than $15\%$ .
Hook Effect
The sponsor demonstrated that there is no hook effect with the assay up to $500,000\mathrm{ng / L}$
3. Analytical Specificity/Interference:
Potentially Interfering Endogenous Substances
A study was performed based on the recommendations in the CLSI EP07, 3rd ed. guideline. Each substance was tested at 2 levels of the analyte (approximately $15\mathrm{ng / L}$ and $500\mathrm{ng / L}$ for bilirubin, total protein, and Intralipid and $15\mathrm{ng / L}$ and $200\mathrm{ng / L}$ for hemoglobin). Test results from samples spiked with the potential interferent were compared to test results from the control samples lacking the potential interferent. No significant interference (results of the
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sample with the potential interferent within ± 10% of the control sample) was observed at the following concentrations.
| Endogenous Substance | Highest Concentration Tested without Significant Interference |
| --- | --- |
| Unconjugated Bilirubin | 40 mg/dL |
| Conjugated Bilirubin | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Total Protein | 8.8 g/dL |
| Triglycerides | 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 | -10.90% |
## Potentially Interfering Drugs and other Compounds
A study was performed based on the recommendations in the CLSI EP07 3rd ed. guideline. Each drug was tested at 2 levels of the analyte (approximately 15 ng/L and 500 ng/L). Test results from samples spiked with the potential interferent were compared to test results from the control samples lacking the potential interferent. No significant interference (results of the sample with the potential interferent within ± 10% of the control sample) was observed at the following concentrations.
| Compound | Highest Concentration Tested Without Interference |
| --- | --- |
| Acetaminophen | 250 μg/mL |
| Acetylsalicylic Acid | 1000 μg/mL |
| Adrenaline | 0.37 μg/mL |
| Allopurinol | 400 μg/mL |
| Ambroxol | 400 μg/mL |
| Ampicillin | 1000 μg/mL |
| Ascorbic Acid | 300 μg/mL |
| Atenolol | 10 μg/mL |
| Biotin | 3510 ng/mL |
| Bivalirudin | 42 μg/mL |
| Caffeine | 100 μg/mL |
| Captopril | 50 μg/mL |
| Carvedilol | 150 μg/mL |
| Cefoxitin | 2500 μg/mL |
| Cinnarizine | 400 μg/mL |
| Clopidogrel | 75 μg/mL |
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| Compound | Highest Concentration Tested Without Interference |
| --- | --- |
| Cocaine | 10 μg/mL |
| Cyclosporine | 5 μg/mL |
| Diclofenac | 50 μg/mL |
| Digoxin | 7.5 μg/mL |
| Dopamine | 900 μg/mL |
| Doxycycline | 50 μg/mL |
| Eptifibatide | 7 μg/mL |
| Erythromycin | 200 μg/mL |
| Fondaparinux | 4 μg/mL |
| Furosemide | 400 μg/mL |
| Ibuprofen | 500 μg/mL |
| Low MW Heparin | 5 U/mL |
| Methyldopa | 25 μg/mL |
| Methylprednisolone | 80 μg/mL |
| Metronidazole | 200 μg/mL |
| Nicotine | 2 μg/mL |
| Nifedipine | 60 μg/mL |
| Nitrofurantoin | 64 μg/mL |
| Nystatin | 7.5 μg/mL |
| Oxytetracycline | 5 μg/mL |
| Phenylbutazone | 400 μg/mL |
| Phenytoin | 100 μg/mL |
| Primidone | 10 μg/mL |
| Propranolol | 5 μg/mL |
| Quinidine | 20 μg/mL |
| Rifampicin | 60 μg/mL |
| Salicylic Acid | 600 μg/mL |
| Simvastatin | 20 μg/mL |
| Sodium Heparin | 8 U/mL |
| Streptokinase | 31.3 U/mL |
| Theophylline | 75 μg/mL |
| TPA | 2.3 μg/mL |
| Trimethoprim | 75 μg/mL |
| Verapamil | 160 μg/mL |
| Warfarin | 30 μg/mL |
Interference beyond ± 10% was observed at the concentration shown below for the following compound.
| Compound | Interferent Level | Analyte Level | % Interference |
| --- | --- | --- | --- |
| Fibrinogen | 1000 mg/dL | 15 ng/L | 24.30% |
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Human anti-mouse antibodies (HAMA) and rheumatoid factor (RF)
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 and 1495 IU/mL and tested with the Alinity i STAT High Sensitivity Troponin-I assay. RF at 1495 IU/mL decreased troponin values up to -18.9%.
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. HAMA at 225 ng/mL decreased troponin values up to -11.0%.
## Cross Reactants
A study was performed based on guidance from CLSI EP07, 3rd ed. Samples with cTnI target concentrations of 2.3, 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. Test results from samples spiked with the potential interferent were compared to test results from the control samples lacking the potential interferent. There was no observed cross-reactivity at the concentrations tested below.
| Potential Cross-Reacting Substance | Highest Concentration Tested (ng/L) |
| --- | --- |
| Actin | 1,000,000 |
| Cardiac Troponin C | 1,000,000 |
| Cardiac Troponin T | 1,000,000 |
| CK-MB | 1,000,000 |
| Myoglobin | 1,000,000 |
| Myosin | 1,000,000 |
| Skeletal Troponin I | 1,000,000 |
| Tropomyosin | 1,000,000 |
The following additional interferences are described in the labeling:
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.
## Limitations
The following limitations are included in the labeling:
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%.
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Specimens from patients who have received preparations of mouse monoclonal antibodies for diagnosis or therapy may contain human anti-mouse antibodies (HAMA). Such specimens may show depressed values when tested with assay kits such as Alinity i STAT High Sensitivity Troponin-I that employ mouse monoclonal antibodies. Additional information may be required for diagnosis.
Heterophilic antibodies in human serum can react with reagent immunoglobulins, interfering with in vitro immunoassays. Patients routinely exposed to animals or to animal serum products can be prone to this interference, and anomalous values may be observed. Additional information may be required for diagnosis.
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%.
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.
Specimens from individuals with elevated levels of fibrinogen may demonstrate falsely elevated values.
4. Assay Reportable Range:
2.7 to 3600.0 ng/L (ng/L) cTnI
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Traceability:
The Abbott Alinity i STAT High Sensitivity Troponin-I is traceable to the National Institute of Standards and Technology (NIST) Standard Reference Material SRM2921. The sponsor's traceability scheme was reviewed and found acceptable.
6. Detection Limit:
Limit of Blank (LoB) Test Protocol
The LoB was determined as described in the CLSI EP17-A2 guideline. Testing was performed using 4 sets of 4 zero-analyte samples tested with 5 replicates on 5 runs over the course of 3 days. Testing was performed using 2 reagent lots and 1 instrument. Sixty determinations were obtained for each reagent lot/instrument combination. LoB was calculated using non-parametric analysis. The largest estimate across all reagent lot-instrument combinations tested was 0.0 ng/L.
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Limit of Detection (LoD) Test Protocol
The LoD was determined following the recommendations in the CLSI EP17-A2 guideline. Testing was performed using 2 reagent lots and 2 instruments. For each lot and instrument combination, at least 5 native low-analyte lithium heparin plasma samples were tested over at least 3 days, with 12 replicates per sample.
The parametric approach described in EP17-A2 was followed to determine the LoD. The largest estimate across all reagent lot-instrument combinations tested was 0.9 ng/L.
Limit of Quantitation (LoQ) Protocol
The LoQ was determined as the analyte level with a within-lab CV of ≤ 20% following the recommendations in the CLSI EP17-A2 guideline. Testing was completed using the same parameters and sampling plan as described above in the LoD Test Protocol. For each reagent lot-instrument combination, the within-laboratory precision for each sample, expressed as %CV, was plotted against the mean concentration obtained for each sample. LoQ was determined by this precision profile as the concentration where the %CV was less than 20%. The largest estimate across all reagent lot-instrument combinations tested was 2.7 ng/L
The sponsor claims a LoB of 0.0 ng/L, and LoD of 0.9 ng/L, and an LoQ of 2.7 ng/L.
7. Assay Cut-Off:
See Clinical Cut-off Section below
B Comparison Studies:
1. Method Comparison with Predicate Device:
Not applicable
2. Matrix Comparison:
A tube type comparison study was carried out following guidance from EP35, 1st Edition on the Alinity i STAT High Sensitivity Troponin-I assay to determine if samples collected in lithium heparin and lithium heparin separator blood collection tubes are equivalent. At least 40 fresh samples were collected in each tube type and then supplemented with native heparin plasma samples to spike concentrations ranging from 2.7 ng/L to 3,500 ng/L. The results indicate concentrations of samples are equivalent when heparin plasma is collected in lithium heparin and lithium heparin separator blood collection tubes.
C Clinical Studies:
1. Clinical Sensitivity:
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 emergency departments (EDs) from diverse locations within the US (i.e., rural and urban, small and
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large, research and non-research) from 6171 subjects presenting to the ED with chest discomfort or equivalent ischemic symptoms consistent with acute coronary syndrome. 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 sample collection times were at 0 - 1 hour from presentation to the ED and at the following time-point relative to the time from presentation: 1 - 3 hours, 3 - 6 hours, and $\geq 6$ hours. Investigators and adjudicators were blinded to the Alinity i STAT High Sensitivity Troponin-I assay device's results. Adjudicators were also blinded to site diagnoses. The observed MI prevalence in this study was $7.0\%$ .
The specimens were collected in lithium heparin or lithium heparin separator tubes and tested within 8 hours of sample collection. The specimens were evaluated using the Alinity i STAT High Sensitivity Troponin-I assay. The results were analyzed using the serial sampling time points collected as part of the ED visit.
The sensitivity and specificity results using the overall 99th percentile cutoff (27 ng/L) are summarized in the following table.
| Sex | Time Point | n | Sensitivity | | Specificity | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | % | 95% CI | % | 95% CI |
| Female | 0 to < 1 Hours | 1,574 | 78.43(80/102) | 69.50 - 85.30 | 89.95(1324/1472) | 88.30 - 91.38 |
| | 1 to < 3 Hours | 841 | 91.49(43/47) | 80.07 - 96.64 | 92.57(735/794) | 90.53 - 94.20 |
| | 3 to < 6 Hours | 854 | 93.85(61/65) | 85.22 - 97.58 | 88.34(697/789) | 85.91 - 90.40 |
| | ≥ 6 Hours | 284 | 94.44(51/54) | 84.89 - 98.09 | 75.65(174/230) | 69.71 - 80.75 |
| Male | 0 to < 1 Hours | 2,917 | 76.45(198/259) | 70.92 - 81.21 | 85.82(2281/2658) | 84.44 - 87.09 |
| | 1 to < 3 Hours | 1,339 | 91.67(77/84) | 83.78 - 95.90 | 85.02(1067/1255) | 82.94 - 86.89 |
| | 3 to < 6 Hours | 1,480 | 93.46(143/153) | 88.39 - 96.41 | 80.71(1071/1327) | 78.50 - 82.74 |
| | ≥ 6 Hours | 576 | 94.44(119/126) | 88.98 - 97.28 | 66.44(299/450) | 61.96 - 70.65 |
The positive predictive value (PPV) and negative predictive value (NPV) results using the overall 99th percentile cutoff $(27\mathrm{ng / L})$ are summarized in the following table.
| Sex | Time Point | n | PPV | | NPV | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | % | 95% CI | % | 95% CI |
| Female | 0 to < 1 Hours | 1,574 | 35.09(80/228) | 29.19 - 41.48 | 98.37(1324/1346) | 97.54 - 98.92 |
| | 1 to < 3 Hours | 841 | 42.16(43/102) | 33.03 - 51.85 | 99.46(735/739) | 98.62 - 99.79 |
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| Sex | Time Point | n | PPV | | NPV | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | % | 95% CI | % | 95% CI |
| | 3 to < 6 Hours | 854 | 39.87 (61/153) | 32.45 - 47.78 | 99.43 (697/701) | 98.54 - 99.78 |
| | ≥ 6 Hours | 284 | 47.66 (51/107) | 38.45 - 57.04 | 98.31 (174/177) | 95.14 - 99.42 |
| Male | 0 to < 1 Hours | 2,917 | 34.43 (198/575) | 30.67 - 38.41 | 97.40 (2281/2342) | 96.67 - 97.97 |
| | 1 to < 3 Hours | 1,339 | 29.06 (77/265) | 23.92 - 34.79 | 99.35 (1067/1074) | 98.66 - 99.68 |
| | 3 to < 6 Hours | 1,480 | 35.84 (143/399) | 31.29 - 40.66 | 99.07 (1071/1081) | 98.31 - 99.50 |
| | ≥ 6 Hours | 576 | 44.07 (119/270) | 38.28 - 50.04 | 97.71 (299/306) | 95.35 - 98.89 |
An analysis for both females and males was performed using the sex-specific 99th percentile cutoffs (female $14\mathrm{ng / L}$ , male $35\mathrm{ng / L}$ ). The sensitivity and specificity results are summarized in the following table.
| Cutoff (ng/L) | Time Point | n | Sensitivity | | Specificity | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | % | 95% CI | % | 95% CI |
| 14 (Female only) | 0 to < 1 Hours | 1,574 | 85.29 (87/102) | 77.15 - 90.88 | 84.04 (1237/1472) | 82.08 - 85.82 |
| | 1 to < 3 Hours | 841 | 93.62 (44/47) | 82.84 - 97.81 | 85.64 (680/794) | 83.03 - 87.91 |
| | 3 to < 6 Hours | 854 | 98.46 (64/65) | 91.79 - 99.73 | 82.00 (647/789) | 79.17 - 84.53 |
| | ≥ 6 Hours | 284 | 98.15 (53/54) | 90.23 - 99.67 | 69.13 (159/230) | 62.89 - 74.75 |
| 35 (Male only) | 0 to < 1 Hours | 2,917 | 72.20 (187/259) | 66.45 - 77.30 | 88.98 (2365/2658) | 87.73 - 90.11 |
| | 1 to < 3 Hours | 1,339 | 89.29 (75/84) | 80.88 - 94.26 | 88.29 (1108/1255) | 86.39 - 89.95 |
| | 3 to < 6 Hours | 1,480 | 90.85 (139/153) | 85.23 - 94.47 | 84.33 (1119/1327) | 82.27 - 86.18 |
| | ≥ 6 Hours | 576 | 92.06 (116/126) | 86.01 - 95.63 | 74.22 (334/450) | 69.99 - 78.05 |
An analysis for both females and males was performed using the sex-specific 99th percentile cutoffs (female $14\mathrm{ng / L}$ , male $35\mathrm{ng / L}$ ). The PPV and NPV results are summarized in the following table.
| Cutoff (ng/L) | Time Point | n | PPV | | NPV | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | % | 95% CI | % | 95% CI |
| 14 (Female only) | 0 to < 1 Hours | 1,574 | 27.02 (87/322) | 22.46 - 32.12 | 98.80 (1237/1252) | 98.03 - 99.27 |
| | | 841 | 27.85 | | 99.56 | |
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| Cutoff (ng/L) | Time Point | n | PPV | | NPV | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | % | 95% CI | % | 95% CI |
| | 1 to < 3 Hours | | (44/158) | 21.45 - 35.30 | (680/683) | 98.72 - 99.85 |
| | 3 to < 6 Hours | 854 | 31.07 (64/206) | 25.14 - 37.69 | 99.85 (647/648) | 99.13 - 99.97 |
| | ≥ 6 Hours | 284 | 42.74 (53/124) | 34.38 - 51.54 | 99.38 (159/160) | 96.55 - 99.89 |
| 35 (Male only) | 0 to < 1 Hours | 2,917 | 38.96 (187/480) | 34.70 - 43.39 | 97.05 (2365/2437) | 96.30 - 97.65 |
| | 1 to < 3 Hours | 1,339 | 33.78 (75/222) | 27.88 - 40.23 | 99.19 (1108/1117) | 98.48 - 99.58 |
| | 3 to < 6 Hours | 1,480 | 40.06 (139/347) | 35.04 - 45.30 | 98.76 (1119/1133) | 97.94 - 99.26 |
| | ≥ 6 Hours | 576 | 50.00 (116/232) | 43.62 - 56.38 | 97.09 (334/344) | 94.73 - 98.41 |
The sponsor provided the following information in their labeling:
When using the female cutoff of $14\mathrm{ng / L}$ , 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 $< 1$ hour), $78.55\%$ (at 1 to $< 3$ hours), $74.86\%$ (at 3 to $< 6$ hours), and $65.62\%$ (at $\geq 6$ hours) of positive troponin results could come from females that are not having an MI. When using the overall cutoff of $27\mathrm{ng / L}$ , the lower bound of the $95\%$ CI for PPV was as low as $29.19\%$ . Taking into consideration the lower bound of the $95\%$ CI, up to $70.81\%$ (at 0 to $< 1$ hour), $66.97\%$ (at 1 to $< 3$ hours), $67.55\%$ (at 3 to $< 6$ hours), and $61.55\%$ (at $\geq 6$ hours) of positive troponin results could come from females that are not having an MI. Troponin results should always be used in conjunction with clinical data, signs, and symptoms.
When using the male cutoff of $35\mathrm{ng / L}$ , the lower bound of the $95\%$ CI for the PPV was as low as $27.88\%$ . Taking into consideration the lower bound of the $95\%$ CI, up to $65.30\%$ (at 0 to $< 1$ hour), $72.12\%$ (at 1 to $< 3$ hours), $64.96\%$ (at 3 to $< 6$ hours), and $56.38\%$ (at $\geq 6$ hours) of positive troponin results could come from males that are not having an MI. When using the overall cutoff of $27\mathrm{ng / L}$ , the lower bound of the $95\%$ CI for PPV was as low as $23.92\%$ . Taking into consideration the lower bound of the $95\%$ CI, up to $69.33\%$ (at 0 to $< 1$ hour), $76.08\%$ (at 1 to $< 3$ hours), $68.71\%$ (at 3 to $< 6$ hours), and $61.72\%$ (at $\geq 6$ hours) of positive troponin results could come from males that are not having an MI. 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.
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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.
The following limitations are in the labeling regarding the clinical performance of this device.
Using the established overall 99th percentile (27 ng/L), the lower end of the 95% confidence interval (CI) for positive predictive value (PPV) for female subjects was as low as 29.19%, and for male subjects was as low as 23.92% in the clinical validation study. Up to 70.81% and 76.08% of positive troponin results could come from females and males, respectively, without an MI.
Using the established sex specific 99th percentiles in the same study (female 14 ng/L, male 35 ng/L), the lower end of the 95% CI for PPV for female subjects was as low as 21.45% and for male subjects was as low as 27.88%. Up to 78.55% and 72.12% of positive troponin results could come from females and males, respectively, without an MI.
False negative rates using the overall cutoff for females and sex-specific cutoff for males were higher compared to the false negative rates using the sex-specific cutoff for females and overall cutoff for males. Refer to the SPECIFIC PERFORMANCE CHARACTERISTICS, Clinical Results section of this package insert.
## 2. Clinical Specificity:
See Clinical Sensitivity above (Section VII. C. 1.).
## D Clinical Cut-Off:
The cut-offs for this assay were determined based on the 99th percentile upper reference limit in apparently healthy adults. Please see Expected Values/Reference Range below (Section VII. E.) for the determination of the clinical cut-offs.
## E Expected Values/Reference Range:
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 the following levels of biomarkers:
| Biomarker | Male | Female |
| --- | --- | --- |
| Cardiac BNP (pg/mL) | ≤ 25 | ≤ 40 |
| HbA1c (%) | ≤ 6 | |
| GFR (mL/min/1.73 m²) | ≥ 60 | |
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Each specimen was stored frozen, thawed, and evaluated in replicates of one using the Abbott ARCHITECT STAT High Sensitivity Troponin-I assay. The 99th percentiles described in the following table for this population were determined using the robust statistical method described in CLSI EP28-A3c.
| Apparently Healthy Population | N | Age Range (years) | 99th Percentile (ng/L) | 90% CI (ng/L) |
| --- | --- | --- | --- | --- |
| Female | 763 | 21-75 | 14 | [12, 17] |
| Male | 766 | 21-73 | 35 | [27, 44] |
| Overall | 1531 | 21-75 | 27 | [22, 32] |
## VIII Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
## IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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