Access hs Tnl

K172783 · Beckman Coulter, Inc. · MMI · Jun 12, 2018 · Clinical Chemistry

Device Facts

• Record ID: K172783
• Device Name: Access hs Tnl
• Applicant: Beckman Coulter, Inc.
• Product Code: MMI · Clinical Chemistry
• Decision Date: Jun 12, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1215
• Device Class: Class 2

Intended Use

Access hsTnI is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma using the UniCel DxI Access Immunoassay Systems to aid in the diagnosis of myocardial infarction (MI).

Device Story

Access hsTnI is an in vitro diagnostic immunoassay used on the UniCel DxI 800 Immunoassay System. It processes human serum or lithium heparin plasma samples to measure cardiac troponin I (cTnI) levels. The device utilizes paramagnetic particles coated with mouse monoclonal anti-human cTnI antibodies and sheep monoclonal anti-human cTnI alkaline phosphatase conjugate in a chemiluminescent sandwich immunoassay format. Operated by laboratory technicians in clinical settings, the system provides quantitative cTnI concentrations. Healthcare providers use these results, compared against established 99th percentile upper reference limits, to assist in the clinical diagnosis of myocardial infarction in patients presenting with ischemic symptoms. The device aids in rapid assessment, potentially facilitating earlier clinical decision-making for patients with suspected acute coronary syndromes.

Clinical Evidence

A multicenter prospective study of 1,854 ED patients with chest pain/ischemic symptoms evaluated diagnostic accuracy. MI incidence was 13%. Sensitivity and specificity were calculated at baseline, 1-3h, 3-6h, and 6-9h intervals. At baseline, overall sensitivity was 88% (95% CI: 80-94) and specificity 89% (95% CI: 86-91). At 3-6 hours, sensitivity reached 94% (95% CI: 89-97) and specificity 90% (95% CI: 88-92). The 99th percentile URL was established in 1,088 healthy subjects (17.9 pg/mL overall for lithium heparin plasma).

Technological Characteristics

Paramagnetic particle, chemiluminescent sandwich immunoassay. Reagents include Dynabeads paramagnetic particles coated with mouse monoclonal anti-human cTnI antibody and sheep monoclonal anti-human cTnI alkaline phosphatase conjugate. Analytical measuring range: 2.1 pg/mL to 27,027 pg/mL. Instrument: UniCel DxI 800. Connectivity: Automated system. Software includes thermal algorithm for assay control.

Indications for Use

Indicated for quantitative determination of cardiac troponin I (cTnI) in human serum and plasma to aid in the diagnosis of myocardial infarction (MI) in patients presenting with chest pain or equivalent ischemic symptoms.

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

• Access AccuTnl+3 Reagent (K121214)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

June 12, 2018

Beckman Coulter, Inc. Kerrie Oetter Staff Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, MN 55318-1084

Re: K172783

Trade/Device Name: Access hsTnI 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 3, 2018 Received: May 4, 2018

Dear Kerrie Oetter:

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. 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

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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.

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 medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

# Kellie B. Kelm -S

for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K172783

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 UniCel DxI Access Immunoassay Systems to aid in the diagnosis of myocardial infarction (MI).

| Type of Use (Select one or both, as applicable) | |
|----------------------------------------------------------------------------------|----------------------------------------------------------------------|
| <input checked="" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D) | <input type="checkbox"/> 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 words "BECKMAN" and "COULTER" stacked on top of each other. The text is in a bold, sans-serif font and is black in color.

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 K172783

# Submitted By:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: [phone] Fax: [phone]

# Contact Person:

Kerrie Oetter 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: [phone] Fax: [phone]

Alternate Contact: Angela Kilian

[phone] [phone] (fax)

# Date Prepared:

June 7, 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 Access UniCel Dxl 800 Immunoassay System comprise the Access Immunoassay System for the quantitative determination of cardiac troponin I (cTnl) in human serum and plasma.

The Access hsTnl 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 UniCel Dxl Access Immunoassay System to aid in the diagnosis of myocardial infarction (MI).

#### Comparison to the Predicates:

The Access hsTnI and the predicate device, Access AccuTnl+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 Device<br>Access AccuTnl+3 for<br>Access 2 Immunoassay<br>Systems – k121214 | New Device<br>Access hsTnl on UniCel Dxl<br>800 Access Immunoassay<br>System |
|---------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use/<br>Indications for<br>Use | The Access AccuTnl+3<br>assay is a paramagnetic<br>particle, chemiluminescent<br>immunoassay for the<br>quantitative determination of<br>cardiac troponin I (cTnI)<br>levels in human serum and<br>plasma using the UniCel Dxl<br>Access Immunoassay<br>System to aid in the<br>diagnosis of myocardial<br>infarction. | Access hsTnl is a<br>paramagnetic particle,<br>chemiluminescent<br>immunoassay for the<br>quantitative determination of<br>cardiac troponin I (cTnI) levels<br>in human serum and plasma<br>using the UniCel Dxl Access<br>Immunoassay System to aid in<br>the diagnosis of myocardial<br>infarction (MI). |
| Assay<br>Principle | Chemiluminescent sandwich<br>immunoassay | Same |
| Test System | Automated immunoassay<br>instrument | Same |
| Sample Type | Serum and heparinized<br>plasma | Same |
| Reagent Pack<br>configuration | Reagents ready to use and<br>separated in a single reagent<br>pack | Same |
| Primary<br>Reagent<br>Materials | Solid phase magnetic<br>particles, anti- cTnl<br>antibodies | Dynabeads* paramagnetic<br>particles coated with mouse<br>monoclonal anti-human cTnl<br>antibody |
| Sample<br>Volume | 55µl | same |
| Specific<br>Reagent<br>Materials | Mouse monoclonal anti-<br>human cTnl alkaline<br>phosphatase conjugate,<br>magnetic particles coated<br>with mouse monoclonal anti-<br>human cTnI | Sheep monoclonal<br>anti - human cTnl alkaline<br>phosphatase conjugate diluted<br>in ACES buffered saline, with<br>surfactant, BSA matrix, protein<br>(bovine, sheep, mouse) |
| Immunoassay<br>Instrument | Access 2 Immunoassay<br>System | UniCel Dxl 800 Access<br>Immunoassay System |
| Analytical<br>Measuring<br>Range | 0.02 ng/mL to 100 ng/mL (20<br>pg/mL to 100,000 pg/mL) | 2.1 pg/mL to 27,027 pg/mL |
| Characteristic | Predicate Device<br>Access AccuTnl+3 for<br>Access 2 Immunoassay<br>Systems – k121214 | New Device<br>Access hsTnl on UniCel Dxl<br>800 Access Immunoassay<br>System |
| Expected<br>Results (Upper<br>Reference<br>Limit) | 99th percentile of 0.02 with a<br>95% Confidence Interval (CI)<br>of 0.01- 0.05 ng/mL | 99th percentile of 17.9 pg/mL with a 95% Confidence Interval (CI) of 14.7 – 27.1 pg/mL for Lithium Heparin Plasma 99th percentile of 18.1 pg/mL with a 95% Confidence Interval (CI) of 14.3 – 25.6 pg/mL for Serum |
| Precision | Total CV of ≤8% at concentrations >0.075 ng/mL. SD ≤0.006 at concentrations ≤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 |
| Open Reagent<br>Pack 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 Protocol<br>File (APF) | AccuTnl+3 APF with addition of the thermal algorithm | hsTnl APF with addition of the thermal algorithm |

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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. Lithium heparin plasma and 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 the 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.

| Sample Type | | Population | N | 99th percentile URL<br>pg/mL (ng/L) | 95% CI<br>pg/mL (ng/L) |
|------------------------------|---------|------------|------|-------------------------------------|------------------------|
| Lithium<br>heparin<br>plasma | Females | 593 | 14.9 | 10.1 - 27.1 | |
| | Males | 495 | 19.8 | 15.9 - 38.4 | |
| | Overall | 1088 | 17.9 | 14.7 - 27.1 | |
| Serum | Females | 592 | 13.6 | 10.0 - 25.6 | |
| | Males | 493 | 19.8 | 15.4 - 44.8 | |
| | Overall | 1085 | 18.1 | 14.3 - 25.6 | |

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 1,854 evaluable subjects from ED patients presenting with chest pain or equivalent ischemic symptoms suggestive of Acute Coronary Syndromes (ACS). A total of 14 geographically diverse, primary care

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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% (238/1854).

Samples were tested at three independent clinical laboratories on Dxl 800 systems. Testing was performed using serum and lithium heparin plasma samples. Study results are shown in Tables 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 |

| 99th<br>percentile<br>URL<br>cutoff,<br>pg/mL<br>(ng/L) | Hours<br>After<br>Admission<br>to ED | Sensitivity | | Specificity | | PPV | | NPV | |
|---------------------------------------------------------|--------------------------------------|-----------------|-----------|-------------------|-----------|-----------------|-----------|-------------------|-----------|
| | | %<br>(n/N) | 95%<br>CI | %<br>(n/N) | 95%<br>CI | %<br>(n/N) | 95%<br>CI | %<br>(n/N) | 95%<br>CI |
| Overall:<br>17.9 | Baseline | 88<br>(89/101) | 80 - 94 | 89<br>(502/567) | 86-91 | 58<br>(89/154) | 50-66 | 98<br>(502/514) | 96-99 |
| | ≥ 1-3 hour | 94<br>(128/136) | 89 - 97 | 90<br>(981/1092) | 88-92 | 54<br>(128/239) | 47-60 | 99<br>(981/989) | 98-100 |
| | ≥ 3-6 hour | 94<br>(143/152) | 89 - 97 | 90<br>(1044/1163) | 88-92 | 55<br>(143/262) | 48-61 | 99<br>(1044/1053) | 98-100 |
| | ≥ 6-9 hour | 99<br>(70/71) | 92-100 | 85<br>(383/450) | 82-88 | 51<br>(70/137) | 42-60 | 100<br>(383/384) | 99-100 |
| Females:<br>14.9 | Baseline | 83<br>(25/30) | 65- 94 | 91<br>(234/256) | 87-95 | 53<br>(25/47) | 38-68 | 98<br>(234/239) | 95-99 |
| | ≥ 1-3 hour | 93<br>(40/43) | 81-99 | 92<br>(490/535) | 89-94 | 47<br>(40/85) | 36-58 | 99<br>(490/493) | 98-100 |
| | ≥ 3-6 hour | 96<br>(48/50) | 86-100 | 92<br>(509/556) | 89-94 | 51<br>(48/95) | 40-61 | 100<br>(509/511) | 99-100 |
| | ≥ 6-9 hour | 100<br>(22/22) | 85-100 | 88<br>(198/225) | 83-92 | 45<br>(22/49) | 31-60 | 100<br>(198/198) | 98-100 |
| Males:<br>19.8 | Baseline | 89<br>(63/71) | 79-95 | 87<br>(271/311) | 83-91 | 61<br>(63/103) | 51-71 | 97<br>(271/279) | 94-99 |
| | ≥ 1-3 hour | 96<br>(89/93) | 89-99 | 88<br>(490/557) | 85-91 | 57<br>(89/156) | 49-65 | 99<br>(490/494) | 98-100 |
| | ≥ 3-6 hour | 94<br>(96/102) | 88-98 | 88<br>(536/607) | 86-91 | 58<br>(96/167) | 50-65 | 99<br>(536/542) | 98-100 |
| | > 6-9 hour | 98<br>(48/49) | 89-100 | 81<br>(183/225) | 76-86 | 53<br>(48/90) | 43-64 | 100<br>(183/184) | 97-100 |

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| 99th<br>percentile<br>URL<br>cutoff,<br>pg/mL<br>(ng/L) | Hours<br>After<br>Admission<br>to ED | Sensitivity | | Specificity | | PPV | | NPV | |
|---------------------------------------------------------|--------------------------------------|-----------------|-----------|--------------------|--------|-----------------|-----------|-------------------|-----------|
| | | %<br>(n/N) | 95%<br>CI | %<br>(n/N) | 95% CI | %<br>(n/N) | 95%<br>CI | %<br>(n/N) | 95%<br>CI |
| Serum | | | | | | | | | |
| Overall:<br>18.1 | Baseline | 87<br>(96/110) | 80-93 | 89<br>(534/598) | 87-92 | 60<br>(96/160) | 52-68 | 97<br>(534/548) | 96-99 |
| | ≥ 1-3 hour | 95<br>(134/141) | 90-98 | 90<br>(999/1110) | 88-92 | 55<br>(134/245) | 48-61 | 99<br>(999/1006) | 99-100 |
| | ≥ 3-6 hour | 95<br>(147/155) | 90-98 | 90<br>(1074/1200) | 88-91 | 54<br>(147/273) | 48-60 | 99<br>(1074/1082) | 99-100 |
| | ≥ 6-9 hour | 97<br>(66/68) | 90-100 | 85<br>(398/468) | 82-88 | 49<br>(66/136) | 40-57 | 100<br>(398/400) | 98-100 |
| Females:<br>13.6 | Baseline | 83<br>(24/29) | 64-94 | 89.4%<br>(237/265) | 85-93 | 46<br>(24/52) | 32-61 | 98<br>(237/242) | 95-99 |
| | ≥ 1-3 hour | 95<br>(41/43) | 84-99 | 91<br>(493/543) | 88-93 | 45<br>(41/91) | 35-56 | 100<br>(493/495) | 99-100 |
| | ≥ 3-6 hour | 96<br>(49/51) | 87-100 | 90<br>(519/579) | 87-92 | 45<br>(49/109) | 35-55 | 100<br>(519/521) | 99-100 |
| | ≥ 6-9 hour | 100<br>(20/20) | 83-100 | 86<br>(202/235) | 81-90 | 38<br>(20/53) | 25-52 | 100<br>(202/202) | 98-100 |
| Males:<br>19.8 | Baseline | 86<br>(70/81) | 77-93 | 87.1%<br>(290/333) | 83-91 | 62<br>(70/113) | 52-71 | 96<br>(290/301) | 94-98 |
| | ≥ 1-3 hour | 96<br>(94/98) | 90-99 | 88<br>(498/567) | 85-90 | 58<br>(94/163) | 50-65 | 99<br>(498/502) | 98-100 |
| | ≥ 3-6 hour | 95<br>(99/104) | 89-98 | 88<br>(546/621) | 85-90 | 57<br>(99/174) | 49-64 | 99<br>(546/551) | 98-100 |
| | ≥ 6-9 hour | 96<br>(46/48) | 86-100 | 82<br>(191/233) | 76-87 | 52<br>(46/88) | 41-63 | 99<br>(191/193) | 96-100 |

Clinical Performance of Access hsTnl Using the Calculated 99th Percentile Cutoffs. Presented at Multiple Time Intervals After Admission to the Emergency Department

Imprecision: The within-laboratory (total) % CV ranged from 2.8% to 10% for hsTnl concentrations ≥ 11.5 pg/mL for serum and lithium heparin plasma samples. The within-laboratory (total) SD ranged from 0.22 to 0.75 for hsTnl for concentrations < 11.5 pg/mL for serum and lithium heparin plasma samples.

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 (2.1 to approximately 27,027 pg/mL) in both serum and lithium heparin plasma samples.

Limit of Blank (LoB): The highest measurement result observed with no analyte present in the samples is 1.2 pg/mL.

Limit of Detection (LoD): The lowest concentration of analyte in both serum and lithium heparin plasma that can be detected is 2.1 pg/mL.

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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 4.6 pg/mL and with within-laboratory imprecision of CV ≤ 20% is 2.1 pg/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 UniCel Dxl 800 instrument within 24 hours of preparation, using three reagent lots. Of the compounds tested, none were found to cause significant cross-reactivity, as defined by a shift in concentration within ± 10% for samples > 11.5 pq/mL. For sample concentrations ≤ 11.5 pg/mL, the change in concentration between diluent control and test sample must be within 2SD, where 2SD is defined as 2.30 pg/mL.

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 pq/mL (ng/L) and 100 pq/mL (ng/L) were spiked with the substances below and run on a single Dxl 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, as defined by a shift in concentration within ± 10% for samples > 11.5 pg/mL. For sample concentrations ≤ 11.5 pq/mL, the change in concentration between diluent control and test sample must be within 2SD, where 2SD is defined as 2.30 pg/mL.

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# Interfering Substances

| Substance | Highest Concentration<br>Added | Substance | Highest Concentration<br>Added |
|--------------------------|--------------------------------|---------------------------------------|--------------------------------|
| 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 Plasminogen<br>Activator (TPA) | 2.5 µg/mL |
| Dopamine | 65 mg/dL | Verapamil | 16 mg/dL |

# Conclusion:

The 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.