(272 days)
Access hsTnl is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnl) levels in human serum and plasma using the Access 2 Immuoasay Systems to aid in the diagnosis of myocardial infarction (MI).
The Access hsTnl and the Access 2 Immunoassay System compose the Access Immunoassay System for the quantitative determination of cardiac troponin I (cTnl) in human serum and plasma.
The Access hsTnI reagent packs contain specific reagents for the in vitro diagnostic measurement of cTnl including:
- R1a: Dynabeads* paramagnetic particles coated with mouse . monoclonal anti-human cTnl antibody suspended in TRIS buffered saline, with surfactant, bovine serum albumin (BSA). < 0.1% sodium azide, and 0.1% ProClin** 300.
- R1b: 0.1 N NaOH .
- R1c: TRIS buffered saline, surfactant, protein (mouse). < 0.1% sodium . azide, and 0.1% ProClin 300.
- R1d: Sheep monoclonal anti-human cTnl alkaline phosphatase conjugate diluted in ACES buffered saline, with surfactant, BSA matrix, protein (bovine, sheep, mouse), < 0.1% sodium azide, and 0.25% ProClin 300.
The provided text describes the Beckman Coulter Access hsTnI diagnostic device, an immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma to aid in the diagnosis of myocardial infarction (MI).
Here's an analysis of the acceptance criteria and study that proves the device meets them:
1. A table of acceptance criteria and the reported device performance
The document provides a comparison of the new device (Access hsTnI) with its predicate device (Access AccuTnI+3 Reagent) and details multiple performance characteristics. The specific acceptance criteria themselves are not explicitly stated as pass/fail thresholds in a dedicated table, but rather implied through the performance data presented and comparison to the predicate. The "Summary of Studies" section details the studies conducted to establish the device's performance, which in effect serves as demonstration of meeting acceptance criteria for analytical and clinical performance.
Implicit Acceptance Criteria and Reported Performance from the Text:
| Feature/Criterion | Predicate Device (Access AccuTnl+3) Performance | New Device (Access hsTnl) Performance |
|---|---|---|
| Intended Use | Aid in diagnosis of MI | Aid in diagnosis of MI |
| Assay Principle | Chemiluminescent sandwich immunoassay | Same |
| Sample Type | Serum and heparinized plasma | Same |
| Analytical Measuring Range | 0.02 ng/mL to 100 ng/mL (20 pg/mL to 100,000 pg/mL) | 2.0 pg/mL to 27,027 pg/mL |
| Expected Results (99th Percentile URL) | 0.02 ng/mL with 95% CI of 0.01-0.05 ng/mL | Lithium Heparin Plasma: - Overall: 17.5 pg/mL (95% CI: 12.6–20.7 pg/mL) - Females: 11.6 pg/mL (95% CI: 8.4–18.3 pg/mL) - Males: 19.8 pg/mL (95% CI: 14.0–42.9 pg/mL) Serum: - Overall: 18.2 pg/mL (95% CI: 13.1–23.1 pg/mL) - Females: 11.8 pg/mL (95% CI: 8.7–18.7 pg/mL) - Males: 19.7 pg/mL (95% CI: 14.3–44.3 pg/mL) |
| Precision | Total CV of ≤8% at >0.075 ng/mL; SD ≤0.006 at ≤0.075 ng/mL | ≤ 10% within-laboratory CV for concentrations ≥ 11.5 pg/mL; ≤ 1.15 pg/mL within-laboratory SD for concentrations < 11.5 pg/mL (Reported ranged from 2.6% to 7.4% for concentrations ≥ 11.5 pg/mL and 0.34 to 0.93 for concentrations < 11.5 pg/mL) |
| Open Reagent Pack Stability | Stable at 2 to 10°C for 56 days | Stable at 2 to 10°C for 64 days |
| Clinical Performance (Sensitivity, Specificity, PPV, NPV) | Not detailed for predicate | Lithium Heparin Plasma (Overall, at Baseline): Sensitivity 86% (86/100), Specificity 90% (510/564), PPV 61% (86/140), NPV 97% (510/524) Serum (Overall, at Baseline): Sensitivity 84% (91/108), Specificity 91% (541/595), PPV 63% (91/145), NPV 97% (541/558) (Detailed results provided for different time intervals and by sex) |
| High-dose Hook Effect | Not detailed for predicate | No high-dose hook effect up to at least 2,000,000 pg/mL |
| Linearity | Not detailed for predicate | Linear across the range of the assay (2.0 to approximately 27,027 pg/mL) in both serum and lithium heparin plasma. |
| Dilution Recovery | Not detailed for predicate | Dilution recovery demonstrated across the range of the assay (2.0 to approximately 27,027 pg/mL) with 10-fold dilution yielding 100 ± 10% recovery for samples from 27,027 to 270,270 pg/mL. |
| Limit of Blank (LoB) | Not detailed for predicate | 0.8 pg/mL |
| Limit of Detection (LoD) | Not detailed for predicate | 2.0 pg/mL in both serum and lithium heparin plasma. |
| Limit of Quantitation (LoQ) | Not detailed for predicate | 4.1 pg/mL (CV ≤ 10%), 2.0 pg/mL (CV ≤ 20%). |
| Analytical Specificity | Not detailed for predicate | No significant cross-reactivity found for tested compounds (defined as concentration shift > ± 2 SD; 10% for > 11.5 pg/mL, 2.30 pg/mL for ≤ 11.5 pg/mL). |
| Interfering Substances | Not detailed for predicate | No significant interference found for tested compounds at specified concentrations (defined as concentration shift > ± 2 SD; 10% for > 11.5 pg/mL, 2.30 pg/mL for ≤ 11.5 pg/mL). |
2. Sample size used for the test set and the data provenance
-
99th percentile URL study:
- Sample Size: 1089 subjects (595 females, 494 males for lithium heparin plasma; 595 females, 493 males for serum).
- Provenance: Multicenter prospective study conducted at five geographically diverse locations throughout the United States.
-
Clinical performance study:
- Sample Size: 1,851 evaluable subjects.
- Provenance: Multicenter prospective study conducted for ED patients presenting with chest pain or equivalent ischemic symptoms suggestive of Acute Coronary Syndromes (ACS). Patients were enrolled from 14 geographically diverse, primary care hospital-associated emergency departments in the United States, reflecting regional, urban, suburban, and rural patient populations.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Ground Truth Experts: An independent panel of expert physicians.
- Qualifications of Experts: Not explicitly stated beyond "expert physicians." However, their role in adjudicating MI statuses using criteria consistent with the Universal Definition of Myocardial Infarction suggests expertise in cardiology and MI diagnosis. They were blinded to assay results and attending physicians' diagnoses.
4. Adjudication method for the test set
- Adjudication Method: "True MI statuses of all subjects were adjudicated by an independent panel of expert physicians using criteria consistent with the Universal Definition of Myocardial Infarction." The specific number of experts involved in the panel (e.g., 2+1, 3+1) is not provided.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- This device is a laboratory immunoassay for measuring a biomarker (cardiac troponin I), not an imaging-based AI diagnostic tool requiring "human readers" or "AI assistance." Therefore, an MRMC comparative effectiveness study, in the context described, was not performed and is not applicable.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- This is a standalone diagnostic assay (algorithm equivalent in this context), as it directly measures cTnI levels. Its performance (sensitivity, specificity, PPV, NPV) was evaluated without direct human intervention in the result generation or interpretation of the assay itself during the study. The study focuses on the diagnostic accuracy of the assay using the established 99th percentile URLs against an expert-adjudicated ground truth. However, the note explicitly states: "The Access hsTnl assay is not intended to be used in isolation; results should be interpreted in conjunction with other diagnostic tests and clinical information," indicating that clinical decision-making ultimately involves a human interpreting the result in context.
7. The type of ground truth used
- Ground Truth Type: Expert consensus. Specifically, "True MI statuses of all subjects were adjudicated by an independent panel of expert physicians using criteria consistent with the Universal Definition of Myocardial Infarction."
8. The sample size for the training set
- The document describes performance studies and reference range establishment. It does not mention a separate "training set" in the context of machine learning. The studies described are for validation and characterization of the assay and its clinical performance. The 99th percentile URL was established using 1089 healthy subjects, and the clinical performance was evaluated on 1,851 evaluable subjects. These represent the datasets used to demonstrate key performance metrics.
9. How the ground truth for the training set was established
- As noted above, the concept of a "training set" in the machine learning sense is not directly applicable here. For the clinical performance evaluation (which is the closest analog to a test set in ML terms for diagnostic accuracy), the ground truth for MI status was established by "an independent panel of expert physicians using criteria consistent with the Universal Definition of Myocardial Infarction."
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June 14, 2018
Beckman Coulter, Inc. Jennifer Bennett Sr. Analyst, Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, MN 55318
Re: K172787
Trade/Device Name: Access hsTnl Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: May 4, 2018 Received: May 7, 2018
Dear Jennifer Bennett:
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 Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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(1-800-638-2041 or 301-796-7100).
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
Sincerely,
(http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone
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
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Indications for Use
510(k) Number (if known) K172787
Device Name Access hsTnI
Indications for Use (Describe)
Access hsTnI is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnl) levels in human serum and plasma using the Access 2 Immuoasay Systems to aid in the diagnosis of myocardial infarction (MI).
| Type of Use (Select one or both, as applicable) | |
|---|---|
X | Prescription Use (Part 21 CFR 801 Subpart D)
| | Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/3/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circle with two white curved lines inside, followed by the company name "BECKMAN COULTER" in bold, black letters. The word "BECKMAN" is stacked on top of the word "COULTER".
Immunodiagnostic Development Center 1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084
510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92(a)(1).
The assigned 510(k) number is K172787
Submitted By:
Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-1142 Fax: (952) 368-7610
Contact Person:
Jennifer Bennett 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-2040 Fax: (952) 368-7704
Alternate Contact: Angela Kilian
(952) 368-1330 (952) 368-7704 (fax)
Date Prepared:
June 12, 2018
Device Name:
Proprietary / Trade Name: Access hsTnl Common Name: Troponin I Enzyme Immunoassay Classification Name: Immunoassay, Troponin Subunits Classification Regulation: 21 CFR 862.1215 Classification Product Code: MMI
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Predicate Devices:
The Access hsTnl claims substantial equivalence to the Access AccuTnl+3 Reagent, FDA 510(k) Number K121214, cleared June 14, 2013.
Device Description:
The Access hsTnl and the Access 2 Immunoassay System compose the Access Immunoassay System for the quantitative determination of cardiac troponin I (cTnl) in human serum and plasma.
The Access hsTnI reagent packs contain specific reagents for the in vitro diagnostic measurement of cTnl including:
- R1a: Dynabeads* paramagnetic particles coated with mouse . monoclonal anti-human cTnl antibody suspended in TRIS buffered saline, with surfactant, bovine serum albumin (BSA). < 0.1% sodium azide, and 0.1% ProClin** 300.
- R1b: 0.1 N NaOH .
- R1c: TRIS buffered saline, surfactant, protein (mouse). < 0.1% sodium . azide, and 0.1% ProClin 300.
- R1d: Sheep monoclonal anti-human cTnl alkaline phosphatase conjugate diluted in ACES buffered saline, with surfactant, BSA matrix, protein (bovine, sheep, mouse), < 0.1% sodium azide, and 0.25% ProClin 300.
*Dynabead® is a registered trademark of Dynal A.S., Osio, Norway **ProClin™ is a trademark of The Dow Chemical Company ("Dow") or an affiliate company of Dow.
Intended Use:
Access hsTnl is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnl) levels in human serum and plasma using the Access 2 Immunoassay System to aid in the diagnosis of myocardial infarction (MI).
Comparison to the Predicates:
The Access hsTnI and the predicate device, Access AccuTnI+3 Reagent, were compared. The information for the predicate device was derived from the predicate device 510(k) Summary and product labeling.
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Comparison of Technological Characteristics to the Predicate (Assay)
| Characteristic | Predicate DeviceAccess AccuTnl+3 forAccess 2 ImmunoassaySystems - K121214 | New DeviceAccess hsTnl on Access 2Immunoassay System |
|---|---|---|
| Intended Use/Indications forUse | The Access AccuTnl+3assay is a paramagneticparticle, chemiluminescentimmunoassay for thequantitative determination ofcardiac troponin I (cTnI)levels in human serum andplasma using the Access 2lmmunoassay System to aidin the diagnosis of myocardialinfarction (MI). | Access hsTnl is aparamagnetic particle,chemiluminescentimmunoassay for thequantitative determination ofcardiac troponin I (cTnl) levelsin human serum and plasmausing the Access 2lmmunoassay System to aid inthe diagnosis of myocardialinfarction (MI) |
| AssayPrinciple | Chemiluminescent sandwichimmunoassay | Same |
| Test System | Automated immunoassayinstrument | Same |
| Sample Type | Serum and heparinizedplasma | Same |
| Reagent Packconfiguration | Reagents ready to use andseparated in a single reagentpack | Same |
| PrimaryReagentMaterials | Solid phase magneticparticles, anti- cTnlantibodies | Dynabeads* paramagneticparticles coated with mousemonoclonal anti-human cTnlantibody |
| SampleVolume | 55μl | Same |
| SpecificReagentMaterials | Mouse monoclonal anti-human cTnl alkalinephosphatase conjugate,magnetic particles coatedwith mouse monoclonal anti-human cTnI | Sheep monoclonalanti - human cTnl alkalinephosphatase conjugate dilutedin ACES buffered saline, withsurfactant, BSA matrix, protein(bovine, sheep, mouse) |
| ImmunoassayInstrument | Access 2 ImmunoassaySystem | Same |
| AnalyticalMeasuringRange | 0.02 ng/mL to 100 ng/mL (20pg/mL to 100,000 pg/mL) | 2.0 pg/mL to 27,027 pg/mL |
| Characteristic | Predicate DeviceAccess AccuTnl+3 forAccess 2 ImmunoassaySystems – K121214 | New DeviceAccess hsTnl on Access 2Immunoassay System |
| ExpectedResults (UpperReferenceLimit) | 99th percentile of 0.02 with a95% Confidence Interval (CI)of 0.01- 0.05 ng/mL | 99th percentile of 17.5 pg/ mLwith a 95% Confidence Interval(CI) of 12.6 – 20.7 pg/mL forLithium Heparin Plasma99th percentile of 18.2 pg/ mLwith a 95% Confidence Interval(CI) of 13.1 - 23.1pg/mL forSerum |
| Precision | Total CV of ≤8% atconcentrations >0.075ng/mL. SD ≤0.006 atconcentrations ≤0.075ng/mL | ≤ 10% within-laboratory CVfor concentrations ≥ 11.5pg/mL ≤ 1.15 pg/mL within-laboratory SD forconcentrations < 11.5pg/mL |
| Open ReagentPack Stability | Stable at 2 to 10°C for 56 days after initial use | Stable at 2 to 10°C for 64 days after initial use |
| Assay ProtocolFile (APF) | AccuTnI+3 APF with additionof the thermal algorithm | hsTnI APF with no thermalalgorithm |
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Summary of Studies
99th percentile URL: A multicenter prospective study was conducted to establish the 99th percentile URL in a population of apparently healthy adults. Serum and lithium heparin plasma samples were evaluated. Subjects ranging from 21 to 99 years of age were enrolled at five qeographically diverse locations throughout the United States. Forty five percent of subjects were ≥ 60 years of age.
Subjects were surveyed and were excluded if they met any of the following criteria:
- . Disease(s) of/or affecting the cardiovascular system
- Currently taking a medication for cardiovascular disease ●
- Diabetes ●
- Chronic kidney disease ●
- Other serious chronic disease(s) (e.g. cancer, COPD, HIV, lupus ● erythematosus, etc.)
- Acute bacterial or viral infection ●
- Pregnancy ●
The 99th percentile URL values determined for lithium heparin plasma (females, males, and overall), and serum (females, and overall) are shown in the following table. All values were determined using the non-parametric statistical method.
| SampleType | Population | N | 99thpercentile | 95% CIpg/mL (ng/L) |
|---|---|---|---|---|
| Lithiumheparinplasma | Females | 595 | 11.6 | 8.4 - 18.3 |
| Males | 494 | 19.8 | 14.0 - 42.9 | |
| Overall | 1089 | 17.5 | 12.6 - 20.7 | |
| Serum | Females | 595 | 11.8 | 8.7 - 18.7 |
| Males | 493 | 19.7 | 14.3 - 44.3 | |
| Overall | 1088 | 18.2 | 13.1 - 23.1 |
99th Percentile URL of a Healthy Population
Clinical performance: A multicenter prospective study was conducted to evaluate the diagnostic accuracy of the Access hsTnl assay using the established 99th percentile URLs. The study was designed to establish the clinical performance of Access hsTnl as an aid in the diagnosis of MI.
The study included 1,851 evaluable subjects from ED patients presenting with chest pain or equivalent ischemic symptoms suggestive of Acute Coronary
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Syndromes (ACS). A total of 14 geographically diverse, primary care hospital-associated emergency departments participated, reflecting regional, urban, suburban, and rural patient populations.
True MI statuses of all subjects were adjudicated by an independent panel of expert physicians using criteria consistent with the Universal Definition of Myocardial Infarction. Adjudicators were blinded to the assay results and the attending physicians' diagnosis. All results presented below were based on the adjudicated diagnoses. The MI incidence was 13% (238/1851).
Samples were tested at three independent clinical laboratories on Access 2 systems. Testing was performed using serum and lithium heparin plasma samples. Study results are shown in Table below. Results are presented for the following time intervals between ED presentation and specimen collection:
• Time of presentation (baseline), ≥1 - 3 hours, ≥ 3 - 6 hours and ≥ 6 - 9 hours after admission
Clinical Sensitivity and Specificity
Diagnostic sensitivity (% MI correctly diagnosed) and specificity (% Non-MI correctly diagnosed) were calculated per CLSI Guideline I/LA21-A2. Estimates of sensitivity and specificity were determined by dividing the number of patients correctly diagnosed by the Access hsTnl assay (n) by the total number of patients with an adjudicated diagnosis (N).
Positive Predictive Value (PPV) and Negative Predictive Value (NPV)
PPV (probability of MI diagnosis in patients with elevated cTnl) and NPV (probability of non-MI diagnosis in patients with non-elevated cTnl) were calculated per CLSI Guideline I/LA21-A2. Estimates of PPV were determined by dividing the number of patients with elevated cTnl values and adjudicated MI diagnoses (n) by the total number of patients with elevated cTnl values (N). Estimates of NPV were determined by dividing the number of patients with non-elevated cTnl values and adjudicated non-MI diagnoses (n) by the total number of patients with non-elevated cTnl values (N).
Predictive value analysis is directly related to the prevalence of disease in the intended use population. The overall MI prevalence of 13% in this study is consistent with literature and public health findings, and indicates that the study population is representative of the intended use population. Since predictive value analysis is prevalence dependent; results will vary by region and facility.
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Clinical Performance of Access hsTnl Using the Calculated 99th Percentile Cutoffs. Presented at Multiple Time Intervals After Admission to the Emergency Department
| 99thpercentileURLcutoff,pg/mL(ng/L) | HoursAfterAdmissionto ED | Sensitivity | Specificity | PPV | NPV | ||||
|---|---|---|---|---|---|---|---|---|---|
| %(n/N) | 95%CI | %(n/N) | 95%CI | %(n/N) | 95%CI | %(n/N) | 95%CI | ||
| Lithium heparin plasma | |||||||||
| Overall:17.5 | Baseline | 86(86/100) | 78-92 | 90(510/564) | 88-93 | 61(86/140) | 53-70 | 97(510/524) | 96 - 99 |
| ≥ 1-3 hour | 95(128/135) | 90-98 | 90(985/1090) | 89-92 | 55(128/233) | 48-61 | 99(985/992) | 99 - 100 | |
| ≥ 3-6 hour | 93(140/151) | 87-96 | 90(1045/1161) | 88-92 | 55(140/256) | 48-61 | 99(1045/1056) | 98 - 100 | |
| ≥ 6-9 hour | 99(70/71) | 92-100 | 86(387/451) | 82-89 | 52(70/134) | 43-61 | 100(387/388) | 99 - 100 | |
| Females:11.6 | Baseline | 90(27/30) | 74-98 | 90(228/254) | 85-93 | 51(27/53) | 37-65 | 99(228/231) | 96 -100 |
| ≥ 1-3 hour | 98(42/43) | 88-100 | 90(482/533) | 88-93 | 45(42/93) | 35 - 56 | 100(482/483) | 99 -100 | |
| ≥ 3-6 hour | 98(48/49) | 89-100 | 89(497/557) | 86-92 | 44(48/108) | 35- 54 | 100(497/498) | 99 -100 | |
| ≥6-9 hour | 100(22/22) | 85 -100 | 84(188/225) | 78-88 | 37(22/59) | 25 - 51 | 100(188/188) | 98 - 100 | |
| Males:19.8 | Baseline | 87(61/70) | 77-94 | 88(272/310) | 84 -91 | 62(61/99) | 51 -71 | 97(272/281) | 94- 99 |
| ≥ 1-3 hour | 95(87/92) | 88-98 | 89(494/557) | 86 - 91 | 58(87/150) | 50-66 | 99(494/499) | 98 - 100 | |
| ≥ 3-6 hour | 92(94/102) | 85-97 | 89(535/604) | 86 - 91 | 58(94/163) | 50-65 | 99(535/543) | 97 - 99 | |
| ≥ 6-9 hour | 98(48/49) | 89-100 | 83(188/226) | 78 - 88 | 56(48/86) | 45 - 67 | 100(188/189) | 97 - 100 |
Note: The Access hsTnl assay is not intended to be used in isolation; results should be interpreted in conjunction with other diagnostic tests and clinical information.
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| 99th percentileURL cutoff,pg/mL (ng/L) | Hours AfterAdmission to ED | Sensitivity | Specificity | PPV | NPV | ||||
|---|---|---|---|---|---|---|---|---|---|
| Serum | %(n/N) | 95% CI | %(n/N) | 95% CI | %(n/N) | 95% CI | %(n/N) | 95% CI | |
| Overall:18.2 | Baseline | 84(91/108) | 76 - 91 | 91(541/595) | 88 – 93 | 63(91/145) | 54-71 | 97(541/558) | 95 – 98 |
| ≥ 1-3 hour | 94(132/141) | 88 – 97 | 91(1009/1108) | 89 - 93 | 57(132/231) | 51-64 | 99(1009/1018) | 98 – 100 | |
| ≥ 3-6 hour | 93(142/152) | 88 - 97 | 90(1082/1202) | 88 - 92 | 54(142/262) | 48-60 | 99(1082/1092) | 98 – 100 | |
| ≥ 6-9 hour | 96(64/67) | 88 - 99 | 86(403/469) | 82 - 89 | 49(64/130) | 40 - 58 | 99(403/406) | 98 – 100 | |
| Females:11.8 | Baseline | 86(25/29) | 68 - 96 | 90(236/263) | 85 - 93 | 48(25/52) | 34-62 | 98(236/240) | 96 – 100 |
| ≥ 1-3 hour | 98(42/43) | 88-100 | 91(491/542) | 88 - 93 | 45(42/93) | 35-56 | 100(491/492) | 99 – 100 | |
| ≥ 3-6 hour | 98(49/50) | 89-100 | 88(512/579) | 86 - 91 | 42(49/116) | 33-52 | 100(512/513) | 99-100 | |
| ≥ 6-9 hour | 100(20/20) | 83-100 | 83(196/235) | 78 - 88 | 34(20/59) | 22-47 | 100(196/196) | 98- 100 | |
| Males:19.7 | Baseline | 86(68/79) | 77 - 93 | 88.0%(292/332) | 84 - 91 | 63(68/108) | 53-72 | 96(292/303) | 94 – 98 |
| ≥ 1-3 hour | 94(92/98) | 87 - 98 | 89(501/566) | 86 - 91 | 59(92/157) | 51-66 | 99(501/507) | 97 - 100 | |
| ≥ 3-6 hour | 93(95/102) | 86 - 97 | 89(553/623) | 86 - 91 | 58(95/165) | 50-65 | 99(553/560) | 97 - 100 | |
| ≥ 6-9 hour | 96(45/47) | 86-100 | 83(193/234) | 77 - 87 | 52(45/86) | 41-63 | 99(193/195) | 96 - 100 |
Clinical Performance of Access hsTnI Using the Calculated 99th Percentile URL Cutoffs. Presented at Multiple Time Intervals After Admission to the Emergency Department
Note: The Access hsTnl assay is not intended to be used in isolation: results should be interpreted inconjunction with other diagnostic tests and clinical information.
Imprecision: The within-laboratory (total) % CV ranged from 2.6% to 7.4% for hsTnl concentrations ≥ 11.5 pg/mL for lithium heparin plasma and serum. The within-laboratory (total) SD ranged from 0.34 to 0.93 for hsTnl for concentrations < 11.5 pq/mL for lithium heparin plasma and serum.
High-dose Hook Effect: The Access hsTnl assay demonstrated no high-dose hook effect up to at least 2,000,000 pg/mL.
Linearity: The Access hsTnl assay has demonstrated to be linear across the range of the assay (2.0 to approximately 27,027 pg/mL) in both serum and lithium heparin plasma samples.
Dilution Recovery: The Access hsTnl assay has been demonstrated to dilute recover across the range of the assay (2.0 to approximately 27.027 pq/mL) in serum and lithium heparin plasma samples. Samples containing troponin I from approximately 27,027 to 270,270 pg/mL can be diluted 10-fold with an average recovery of 100 ± 10%.
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Limit of Blank (LoB): The highest measurement result observed with no analyte present in the samples is 0.8 pq/mL.
Limit of Detection (LoD): The lowest concentration of analyte in both serum and lithium heparin plasma that can be detected is 2.0 pg/mL.
Limit of Quantitation (LoQ): The lowest concentration of analyte in both serum and lithium heparin plasma samples that can be quantitatively determined with within-laboratory imprecision of CV ≤ 10% is 4.1 pg/mL and with within-laboratory imprecision of CV ≤ 20% is 2.0 pq/mL.
Analytical Specificity: Potential cross-reactive substances were added to lithium heparin plasma and serum samples at two concentrations of cTnl (approximately 10 pq/mL and one containing approximately 100 pg/mL) Stock solutions of potential cross-reactants were prepared volumetrically using calibrated pipettes and the appropriate solvent. This stock solution was added directly to the lithium heparin plasma and serum samples in no more than 5% (v/v) final concentration. Control samples were prepared in the same manner using the solvent, without the cross-reactant added. Control and test samples were tested on the Access 2 instrument within 24 hours of preparation, using three reagent lots. Of the compounds tested, none were found to cause significant cross-reactivity at the levels listed in the table below, as defined by a shift in concentration greater than ± 2 standard deviation (SD). For sample concentrations > 11.5 pg/mL (ng/L), 2 SD is defined as 10%. For sample concentrations ≤ 11.5 pq/mL (ng/L), 2SD is defined as 2.30 pg/mL (ng/L).
Interfering Substances: Potential interferents were tested at one concentration within the reference interval or the therapeutic concentration range as directed by EP7-A2 (Interference Testing in Clinical Chemistry-Approved Guideline, Second Edition). Lithium heparin plasma and serum samples containing cTnl concentrations of approximately, 10 pg/mL (ng/L) and 100 pg/mL (ng/L) were spiked with the substances below and run on a single Access 2 Immunoassay System. Interference was determined by testing controls (no interfering substance added) and matched test samples (with interfering substance added). Of the compounds tested, none were found to cause significant interference at the levels listed in the table below, as defined by a shift in concentration greater than ± 2SD. For sample concentrations > 11.5 pg/mL (ng/L), 2SD is defined as 10%. For sample concentrations ≤ 11.5 pg/mL (ng/L), 2SD is defined as 2.30 pq/mL (nq/L).
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| Substance | Highest ConcentrationAdded | Substance | Highest ConcentrationAdded |
|---|---|---|---|
| Acetaminophen | 50 mg/dL | Fibrinogen | 1000 mg/dL |
| Acetylsalicylic Acid | 65 mg/dL | Furosemide | 40 mg/dL |
| Atenolol | 1 mg/dL | Hemoglobin | 4 mg/mL |
| Atorvastatin | 20 µg/mL | Human Serum Albumin | 6000 mg/dL |
| Bilirubin (conjugated) | 40 mg/dL | Ibuprofen | 50 mg/dL |
| Bilirubin (unconjugated) | 20 mg/dL | Intralipid | 3000 mg/dL |
| Bivalirudin | 42 µg/mL | Sodium Heparin | 28.8 U/mL |
| Caffeine | 10 mg/dL | Methyldopa | 2.5 mg/dL |
| Captopril | 5 mg/dL | Nitrofurantoin | 6.4 mg/dL |
| Cinnarizine | 40 mg/dL | Nystatin | 2 mg/dL |
| Clopidogrel | 75 µg/mL | Phenobarbital | 20 µg/mL |
| Cocaine | 2 mg/dL | Rifampicin | 60 µg/mL |
| Cyclosporine | 5 µg/mL | Rosuvastatin | 20 µg/mL |
| Digoxin | 200 ng/mL | Tissue PlasminogenActivator (TPA) | 2.5 µg/mL |
| Dopamine | 65 mg/dL | Verapamil | 16 mg/dL |
Interfering Substances
Conclusion:
Access hsTnl is equivalent to the currently marketed Access AccuTnl+3 assay. The verification and validation data provided in this submission demonstrates that the safety and efficacy of this device is equivalent to the Access AccuTnl+3 predicate device.
§ 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.