The Access AccuTnl+3 Reagent 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.

The Access AccuTnl+3 Calibrators are intended to calibrate the Access AccuTnl+3 Reagent 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.

The Access 2 Immunoassay System is an in vitro diagnostic device used for the quantitative, semi-quantitative, or qualitative determination of various analyte concentrations found in human body fluids.

Device Description

The Access AccuTnl+3 reagents, AccuTnl+3 calibrators and the Access 2 Immunoassay System compose the Access Immunoassay System for the quantitative determination of cardiac troponin I (cTn!) in human serum and plasma.

The Access AccuTnI+3 reagent packs contain specific reagents for the in vitro diagnostic measurement of cTnI including:

Paramagnetic particles coated with mouse monoclonal anti-human cardiac . troponin I suspended in TRIS buffered saline, with surfactant, bovine serum albumin (BSA) matrix. <0.1% sodium azide, and 0.1% ProClin® 300.
0.1N NaOH. .
. TRIS buffered saline, surfactant, <0.1% sodium azide and 0.1% ProClin 300.
Mouse monoclonal anti-human cTnI alkaline phosphatase conjugate . diluted in ACES buffered saline, with surfactant, BSA matrix, protein (bovine, goat, mouse), <0.1% sodium azide, and 0.25% ProClin 300.

The Access AccuTnl+3 Calibrator set contains multi-point calibrators for use with the Access AccuTnI+3 assay. Individual vials contain zero or approximately 0.3. 1.2, 5.0, 25 and 100 ng/mL (ug/L) of recombinant cardiac troponin I complex. respectively, in a buffered BSA matrix, with surfactant, <0.1% sodium azide, and 0.1% ProClin 300.

AI/ML Overview

The Access AccuTnI+3 Reagent, AccuTnI+3 Calibrators, and Access 2 Immunoassay System constitute the Access Immunoassay System. This system aims to quantitatively determine cardiac troponin I (cTnI) in human serum and plasma to assist in diagnosing myocardial infarction.

Here's an analysis of the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document compares the new device (Access AccuTnI+3 Reagent and Calibrators) with a predicate device (ADVIA Centaur TnI-Ultra Assay) and the new Access 2 Immunoassay System with a predicate Access 2 Immunoassay System. The "acceptance criteria" are implied by the performance characteristics presented, demonstrating equivalence or improvements over the predicate devices.

Acceptance Criteria (Implied by Predicate Performance) and Reported Device Performance (New Device)

Characteristic	Predicate Device (ADVIA Centaur® TnI-Ultra™)	New Device (Access AccuTnI+3 Reagent and Calibrators)	Difference/Improvement (New vs. Predicate)
Analyte	Cardiac Troponin I	Cardiac Troponin I	Same
Sample Type (Main)	Serum and heparinized plasma (also EDTA plasma claim)	Serum and plasma (No EDTA plasma claim)	New device does not support EDTA plasma.
Assay Principle	Chemiluminescent sandwich immunoassay	Chemiluminescent sandwich immunoassay	Same
Test System	Automated immunoassay instrument	Automated immunoassay instrument (Access 2 Immunoassay System)	Same type of system.
Analytical Measuring Range	0.008 ng/mL to 50 ng/mL	0.02 ng/mL to 100 ng/mL	Wider upper detection limit (up to 100 ng/mL vs. 50 ng/mL).
AMI Cutoff (WHO-defined)	0.9 ng/mL	0.03 ng/mL	Significantly lower cutoff, suggesting higher sensitivity for AMI diagnosis.
Expected Results (99th %tile URL)	0.04 ng/mL; range of 0.02-0.06 ng/mL	0.02 ng/mL with a 95% Confidence Interval (CI) of 0.01-0.05 ng/mL	Lower 99th percentile URL, indicating better differentiation of healthy vs. MI.
Precision	Total CV of 10% at 0.042 ng/mL	Total CV of ≤8% at concentrations >0.075 ng/mL. SD ≤0.006 at concentrations ≤0.075 ng/mL	Improved precision (lower CV) at higher concentrations and lower SD at lower concentrations.
Sample Volume	100μL	55μL	Smaller sample volume required.

Access 2 Immunoassay System (New vs. Predicate)

Characteristic	Predicate Device (Access 2 System K922823/A007)	New Device (Access 2 Immunoassay System)	Difference/Improvement (New vs. Predicate)
Thermal algorithm capability	Not present	Present	New feature: enhanced thermal algorithm.
Software	Version 2.4-3.2	Version 3.3: added capability to implement thermal algorithm and "U" Command; added result suppression when instrument internal case temperature is outside 18° to 36°C	Improved software with new functionalities and safety features.
Operating Temperature	18°C to 32°C ambient	18°C to 28°C ambient (18°C to 36°C internal)	Narrower ambient operating temperature range, but wider internal temperature monitoring.

The study demonstrates that the new device meets or exceeds the critical performance characteristics of the predicate device for clinical utility (e.g., sensitivity, measuring range, precision) and introduces enhanced features in the accompanying instrument system.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

The document explicitly states:

AMI Cutoff: "0.03ng/mL based on clinical trial outcome"
Expected Results (99th percentile URL): "99th percentile of 0.02 with a 95% Confidence Interval (CI) of 0.01-0.05 ng/mL"

However, the specific sample size for this clinical trial, the data provenance (e.g., country), or whether it was retrospective or prospective are not detailed in the provided text.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

The document states that the AMI cutoff is "based on clinical trial outcome" and the 99th percentile URL is derived from a reference population. However, it does not specify the number or qualifications of experts used to establish the ground truth or interpret the clinical trial outcomes. The diagnosis of myocardial infarction typically involves clinical judgment by cardiologists, but the role of experts in establishing the ground truth for the test set (e.g., for sample classification) is not described.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

The document does not provide any information on the adjudication method used for the test set.

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 an immunoassay system for measuring a biomarker (Troponin I), not an imaging diagnostic device typically evaluated with MRMC studies or human-in-the-loop AI assistance. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable to this type of device and was not mentioned.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the performance characteristics (Analytical Measuring Range, AMI Cutoff, Expected Results, Precision) presented in the table are standalone performance metrics of the Access AccuTnI+3 Reagent and Access 2 Immunoassay System. This device is an automated in vitro diagnostic test, meaning its output (cTnI concentration) is generated by the algorithm/system without direct human-in-the-loop interpretation changing the result itself. Human clinicians then use this quantitative result to aid in diagnosis.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth used for the AMI cutoff and expected results seems to be based on:

"Clinical trial outcome" for the AMI cutoff (implying patient diagnosis and potentially follow-up outcomes).
"99th percentile" for the upper reference limit, which is typically established by testing a large cohort of apparently healthy individuals.

The document does not explicitly state "expert consensus," "pathology," or "outcomes data" as the ground truth, but "clinical trial outcome" suggests reliance on established clinical diagnostic criteria for myocardial infarction for the first, and a healthy reference population for the second.

8. The sample size for the training set

The document does not specify a training set sample size. For an immunoassay, the "training set" would typically refer to the data used during assay development and optimization (e.g., reagent formulation, calibration curve development), rather than a machine learning context. The document focuses on the performance verification of the final device.

9. How the ground truth for the training set was established

As there is no explicit mention of a "training set" in the context of machine learning, the question of how its ground truth was established is not directly addressed. For the development of the assay, the ground truth would inherently come from known concentrations of cTnI in spiked samples, reference materials, and characterized clinical samples used during method development and validation.

Summary

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510(k) Summary

JUN 1 4 2013

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92

The assigned 510(k) number is K121214

Submitted By:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-1142 Fax: (952) 368-7610

Contact Person:

Kerrie Oetter 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-7858 Fax: (952) 368-7610

Date Prepared:

June 12, 2013

Device Name:

Proprietary / Trade Name: Access AccuTn1+3 Reagent for use on the Access 2 Immunoassay Systems Common Name: Troponin I Enzyme Immunoassay Classification Name: Immunoassay, Troponin Subunits Classification Regulation: 21 CFR 862.1215 Classification Product Code: MMI

Proprietary / Trade Name: Access AccuTnI+3 Calibrator Common Name: Calibrator Classification Name: Calibrator Classification Regulation: 21 CFR 862.1150 Subsequent Product Code: JIT

Proprietary / Trade Name: Access 2 Immunoassay System Common Name: Discrete photometric chemistry analyzer for clinical use Classification Name: Discrete photometric chemistry analyzer for clinical use Classification Regulation: 21 CFR 862.2160 Classification Product Code: JJE

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Predicate Devices:

The Access AccuTnl+3 Reagent and AccuTnl+3 Calibrators claim substantial equivalence to the ADVIA Centaur TnI-Ultra™ Assay and ADVIA Centaur TnI-Ultra™ Calibrators for the Siemens ADVIA Centaur® System. FDA 510(k) Number K053020, cleared December 30, 2005.

The Access 2 Immunoassay System claims substantial equivalence to the Access 2 Immunoassay System (K922823/A007), cleared July 2, 2001.

Device Description:

The Access AccuTnI+3 reagent packs contain specific reagents for the in vitro diagnostic measurement of cTnI including:

Paramagnetic particles coated with mouse monoclonal anti-human cardiac . troponin I suspended in TRIS buffered saline, with surfactant, bovine serum albumin (BSA) matrix. <0.1% sodium azide, and 0.1% ProClin® 300.
0.1N NaOH. .
. TRIS buffered saline, surfactant, <0.1% sodium azide and 0.1% ProClin 300.
Mouse monoclonal anti-human cTnI alkaline phosphatase conjugate . diluted in ACES buffered saline, with surfactant, BSA matrix, protein (bovine, goat, mouse), <0.1% sodium azide, and 0.25% ProClin 300.

Intended Use:

The Access AccuTnI+3 Reagent 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.

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The Access AccuTnI+3 Calibrators are intended to calibrate the Access AccuTnI+3 Reagent 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.

Comparison to the Predicates:

The Access AccuTnI+3 Reagent and Access AccuTnl+3 Calibrators and the predicate device, ADVIA Centaur® TnI-Ultra™ Assay and ADVIA Centaur® · Tnl-Ultra™ Calibrators, were compared. The information for the predicate device was derived from the predicate device 510(k) Summary and product labeling.

Similarities between the Access AccuTnI+3 Reagent and Access AccuTnI+3. Calibrators and the Predicate

Characteristic	Predicate DeviceADVIA Centaur® TnI-UltraTMK053020	New DeviceAccess AccuTnI+3 Reagent andAccess AccuTnI+3Calibrators
Intended Use	An in vitro diagnostic method for thequantitative measurement of cardiacTnI in serum and plasma to aid in thediagnosis of myocardial infarction.	same
Assay Principle	Chemiluminescent sandwichimmunoassay	same
Test System	Automated immunoassay instrument	same
Sample Type	Serum and heparinized plasma	same
Reagent Packconfiguration	Reagents ready to use and separated ina single reagent pack	same
Primary ReagentMaterials	Solid phase magnetic particles, anti-cTnI antibodies	same

Differences between the Access AccuTnI+3 Reagent and Calibrator and the Predicate

Characteristic	Predicate DeviceADVIA Centaur® TnI-Ultra™K053020	New DeviceAccess AccuTnl+3 Reagent and AccessAccuTnl+3 Calibrators
Sample Type	EDTA plasma	No EDTA plasma claim
ImmunoassayInstrument	ADVIA Centaur	Access 2 Immunoassay System
CalibratorMaterials	Bovine cTnI in goat serum	Recombinant troponin complex in bufferedBSA
Calibrators:number and type	Two Lyophilized : high and low (usewith Master Curve)	Six Liquid: approximately 0, 0.3, 1.2, 5.0,25 and 100 ng/mL with no master curve
	Predicate Device	New Device
Characteristic	ADVIA Centaur® Tnl-Ultra™K053020	Access AccuTnI+3 Reagent and AccessAccuTnI+3 Calibrators
Specific ReagentMaterials	Polyclonal goat anti-cTnI antibodylabeled with acridinium ester, 2biotinylated mouse monoclonal anti-cTnI antibodies, magnetic particlesconjugated with streptavidin	Mouse monoclonal anti-human cTnIalkaline phosphatase conjugate, magneticparticles coated with mouse monoclonalanti-human cTnI
Sample Volume	100μl	55μl
AnalyticalMeasuring Range	0.008 ng/mL to 50 ng/mL	0.02 ng/mL to 100 ng/mL
Acute MyocardialInfarction (AMI)Cutoff	0.9 ng/mL per WHO-defined cutoff	0.03ng/mL based on clinical trial outcome
Expected Results(Upper ReferenceLimit)	99th percentile of 0.04 ng/mL; range of0.02- 0.06 ng/mL	99th percentile of 0.02 with a 95%Confidence Interval (CI) of 0.01- 0.05ng/mL
Precision	Total CV of 10% at a level of 0.042ng/mL	Total CV of ≤8% at concentrations >0.075ng/mL. SD ≤0.006 at concentrations≤0.075 ng/mL
Indications forUse Statement	The ADVIA Centaur® Tnl-Ultra (TnlUltra) is for in vitro diagnostic use-inthe quantitative determination ofcardiac Troponin in human serum andheparinized and EDTA plasma.Cardiac troponin I determinations aidin the diagnosis of acute myocardialinfarction and in the risk stratificationof patients with non-ST segmentelevation acute coronary syndromeswith respective to relative riskmortality, myocardial infarction orincreased probability of ischemicevents requiring urgentrevascularization procedures.The ADVIA Centaur® TnI-UltraCalibrator is for the in-vitro diagnosticuse in the calibration of the TnI-Ultraassay on the ADVIA Centaur®System.	The Access AccuTnI+3 assay is aparamagnetic particle, chemiluminescentimmunoassay for the quantitativedetermination of cardiac troponin I (cTnI)levels in human serum and plasma usingthe Access 2 Immunoassay System to aidin the diagnosis of myocardial infarction.The Access AccuTnI+3 Calibrators areintended to calibrate the AccessAccuTnI+3 assay for the quantitativedetermination of cardiac troponin I (cTnI)levels in human serum and plasma usingthe Access 2 Immunoassay System to aidin the diagnosis of myocardial infarction.

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The Access 2 Immunoassay System and the previously cleared version of the Access 2 Immunoassay System were compared.

・

..... .

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Characteristic	Predicate DeviceAccess 2 SystemK922823/A007	New DeviceAccess 2 Immunoassay System
Indication for Use	The Access 2 Immunoassay system isan in vitro diagnostic device used forthe quantitative, semi-quantitative, orqualitative determination of variousanalyte concentrations found in humanbody fluids.	same
OperatingPrinciple	Micro computer controlled, randomand continuous access	same
Assay Type	Enzyme immunoassays	same
Detection	Chemiluminescent	same
Modules	Carousel, pipettor, analytical, fluidic,electronic/systems computer/peripheral	same

Similarities between the Access 2 Immunoassay System and the Predicate

Differences between the Access 2 Immunoassay System and the Predicate

Characteristic	Predicate DeviceAccess 2 Immunoassay SystemK922823/A007	New DeviceAccess 2 Immunoassay System
Thermal algorithmcapability	Not present	Present
Assay ProtocolFile (APF)	AccuTnl APF	AccuTnl APF with addition of the thermalalgorithm and "U" command
Software	Version 2.4-3.2	Version 3.3: added capability to implementthe thermal algorithm and "U" Command;added result suppression when instrumentinternal case temperature is outside 18° to36°C
OperatingTemperature	18°C to 32°C ambient	18°C to 28°C ambient18°C to 36°C

Conclusion: The information provided above demonstrates that the new device, the Access AccuTnI+3 Reagent and Access AccuTnI+3 Calibrators, have the same intended use as the predicate device. The Access 2 instrument has the same intended use as the predicate device. In addition, verification and validation testing, the clinical and analytical data, the clinical use of the product reflected in current MI diagnostic guidelines, and other scientific information provided in this submission demonstrate that the Access AccuTnI+3 Reagent, Access AccuTnI+3 Calibrators on the Access 2 Immunoassay Systems is as safe and effective as the predicate devices. Taken together, this information establishes the substantial equivalence of Beckman Coulter's products to predicates.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features a staff with a snake winding around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged in a circular fashion around the symbol. The text is in all caps and is smaller than the caduceus symbol.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

June 14, 2013

Beckman Coulter, Inc. C/O Kerrie Oetter 1000 Lake Hazeltine Drive CHASKA MN 55318-1084

Re: K121214

Trade/Device Name: Access AccuTnl+3 Reagent and Access AccuTnl+3 Calibrators for use on the Access 2 Immunoassay Systems

Regulation Number: 21 CFR 862.1215

· Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: II Product Code: MMI, JIT, JJE Dated: June 04, 2013 Received: June 06, 2013

Dear Ms. Oetter:

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: - GDRH-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); medical device reporting (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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Page 2-Ms. Oetter

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Courtney Hillias, Ph.D.

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 Form

510(k) Number (if known): K121214

Device Name: Access AccuTnl+3 Reagent and Access AccuTnl+3 Calibrators for use on the Access 2 Immunoassay Systems

Indications for Use:

Prescription Use x Prescription Use _____________________________________________________________________________________________________________________________________________________________

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Ruth A. Chešler/S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

K121214 510(k)

Regulation Number and Section

§ 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.