The Access AccuTnl+3 Reagent for use on the UniCel Dxl Access Immunoassay Systems is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnl) levels in human serum and plasma using the UniCel Dx1 Acess Immunoassay Systems to aid in the diagnosis of myocardial infarction.

The Access AccuTnI+3 Calibrators for use on the UniCel DxI Access Immunoassay Systems are intended to calibrate the Access AccuTn1+3 Reagent 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.

The UniCel DxI 800 Access 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 AccuTnI+3 Reagents, AccuTn1+3 Calibrators and the UniCel Dx1 800 Access Immunoassay System compose the Access Immunoassay System for the quantitative determination of cardiac troponin I (cTnl) in human serum and plasma.

The Access AccuTnl+3 Reagent packs contain specific reagents for the in virro diagnostic measurement of cTnl including:

Paramagnetic particles coated with mouse monoclonal anti-human cardiac troponin I (cTnl) 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 AccuTnI+3 Calibrator set contains multi-point calibrators for use with the Access AccuTnI+3 assay. Each vial contains zero and approximately 0.2, 0.9, 3.7, 20 and 80 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.

the UniCel DxI 800 Access 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.

AI/ML Overview

Here's an analysis of the provided 510(k) summary, specifically focusing on the acceptance criteria and the study proving the device meets them:

Disclaimer: This response is based solely on the provided text. A full understanding of the device's performance would require reviewing the complete 510(k) submission and potentially additional studies. The document provided is a summary, meaning it may not contain all the detailed information typically found in a full study report.

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on comparing the new device (Access AccuTnI+3) to a predicate device (ADVIA Centaur® TnI-Ultra™). While it lists some characteristics for both, explicit "acceptance criteria" for the new device's performance that it must meet are not clearly delineated as pass/fail thresholds in a dedicated section. However, performance characteristics are reported in the comparison table, which implicitly act as the device's claimed performance.

For the purpose of this request, I will extract relevant performance characteristics from the "Differences between the Access AccuTnI+3 Reagent and Calibrator and the Predicate" table, as these are the new device's specific claims, and then discuss what can be inferred as "acceptance."

Characteristic	Acceptance Criteria (Implied / Comparator)	Reported Device Performance (Access AccuTnI+3)
Analytical Measuring Range	Predicate: 0.008 ng/mL to 50 ng/mL (The new device is implicitly accepting that its range is adequate, whether narrower or wider, as long as it supports the intended use. In this case, the range is different but considered acceptable for the intended use of aiding in MI diagnosis.)	0.03 ng/mL to 80 ng/mL (This is the stated measuring range of the Access AccuTnI+3.)
Acute Myocardial Infarction(AMI) Cutoff	Predicate: 0.78 ng/mL per WHO-defined cutoff (The new device demonstrates a different cutoff, but implies it is clinically validated.)	0.03 ng/mL based on clinical trial outcome (This is the specific AMI cutoff determined for the Access AccuTnI+3 through its clinical trial.)
Expected Results (UpperReference Limit)	Predicate: 99th percentile of 0.04 ng/mL; range of 0.02-0.06 ng/mL (The new device's URL is presented as its own derived value, implying it's acceptable for clinical use.)	99th percentile upper reference limit (URL) is < 0.03 ng/mL with a 97.5% upper confidence limit of 0.04 ng/mL (This is the specific 99th percentile URL for Access AccuTnI+3.)
Precision	Predicate: Total CV of 10% at a level of 0.03 ng/mL (The new device demonstrates better or equivalent precision compared to a competitive standard, implying its performance is acceptable.)	Total CV of ≤8% at concentrations >0.075 ng/mL. SD ≤0.006 at concentrations ≤0.075 ng/mL (These are the stated precision characteristics for Access AccuTnI+3. The low end precision (SD) shows particular attention to the critical low-level measurements.)

Study Proving Device Meets Acceptance Criteria:

The document states: "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 UniCel DxI Access Immunoassay Systems is as safe and effective as the predicate devices."

This statement indicates that a combination of verification and validation (V&V) testing, along with clinical and analytical data, was submitted to support the device's claims and its substantial equivalence to the predicate. The specific studies mentioned directly related to establishing the AMI cutoff and the 99th percentile URL are:

"0.03 ng/mL based on clinical trial outcome" for the AMI Cutoff.
"99th percentile upper reference limit (URL) is < 0.03 ng/mL with a 97.5% upper confidence limit of 0.04 ng/mL" for Expected Results. This implies a reference interval study was conducted.
"Total CV of ≤8% at concentrations >0.075 ng/mL. SD ≤0.006 at concentrations ≤0.075 ng/mL" for Precision. This would be established through a precision study.

Missing Information: The summary does not provide granular details about the methodologies, specific sample sizes, or results of these individual studies beyond the final reported performance values. It states these data were "provided in this submission," implying they exist in the full 510(k) filing.

Detailed Information for Study That Proves the Device Meets Acceptance Criteria:

Based on the provided text, many details about the specific studies are not included in this 510(k) summary. The summary is a high-level overview.

2. Sample Size Used for the Test Set and Data Provenance:

Test Set Sample Size: Not explicitly stated for any of the studies (e.g., clinical trial for AMI cutoff, reference interval study, precision study).
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The mention of "clinical trial outcome" for the AMI cutoff implies a prospective study.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

Number of Experts: Not explicitly stated.
Qualifications of Experts: Not explicitly stated.
Given this is an immunoassay for a biomarker (troponin I), the ground truth for clinical outcomes like Myocardial Infarction would typically be established by a panel of cardiologists or emergency physicians, using a comprehensive assessment including clinical presentation, ECG changes, and serial biomarker measurements (often the device under study itself or a comparator, combined with other clinical judgment). For analytical performance (e.g., precision), laboratory experts would define ground truth or test methods.

4. Adjudication Method for the Test Set:

Adjudication methods (e.g., 2+1, 3+1) are typically relevant for studies where expert readers or clinicians interpret images or clinical data to determine a diagnosis. For a quantitative immunoassay, the "ground truth" for myocardial infarction would generally involve comprehensive clinical criteria, including expert diagnosis, but the document does not detail how this clinical ground truth was adjudicated.
For analytical studies (e.g., precision, analytical measuring range), adjudication methods are not typically applicable.

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:

No, an MRMC comparative effectiveness study was not done. This type of study is specific to imaging devices, often involving AI algorithms, where human readers interpret images. The device here is an immunoassay system for a biochemical marker (cardiac troponin I), not an imaging device with AI assistance for human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, the device's performance is inherently standalone. The Access AccuTnI+3 Reagent and UniCel DxI Access Immunoassay System produce a quantitative measurement of cTnI. The "performance" reported (analytical measuring range, AMI cutoff, 99th percentile URL, precision) are all standalone performance characteristics of the assay system itself. There isn't a "human-in-the-loop" component for the measurement of troponin I. The physician then uses this measurement, along with other clinical information, to make a diagnosis.

7. The Type of Ground Truth Used:

For Analytical Performance (Analytical Measuring Range, Precision): Ground truth is typically established by reference methods or gravimetric/volumetric preparation of standards.
For Clinical Performance (AMI Cutoff, Expected Results/99th percentile URL):
- AMI Cutoff: "0.03 ng/mL based on clinical trial outcome." This implies that the ground truth for "myocardial infarction" was based on clinical diagnosis following established guidelines (e.g., WHO or ESC/ACC definitions available at the time) in the patient population studied in the clinical trial. This diagnosis would involve expert clinical judgment based on a combination of symptoms, ECG findings, and serial cardiac biomarker measurements (potentially including confirmed MI by a different, reference assay or the device itself as part of a comprehensive clinical picture).
- Expected Results (99th percentile URL): This is established by measuring cTnI levels in a healthy reference population and determining the 99th percentile value.

8. The Sample Size for the Training Set:

Not explicitly stated. The summary does not provide any details about a "training set" or "validation set" in the context of an algorithm. For an immunoassay, the concept of training set might refer to reagent formulation and calibration curve development, but specific sample sizes for these are not provided.

9. How the Ground Truth for the Training Set Was Established:

Not applicable in the context of a "training set" for an AI algorithm. As this is an immunoassay, the "ground truth" for developing the assay (e.g., calibrators) would be based on precisely characterized reference materials (e.g., recombinant cardiac troponin I complex at known concentrations, as mentioned in the device description).

Summary

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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

The assigned 510(k) number is K121790

Submitted By:

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

Contact Person:

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

Date Prepared:

September 23, 2013

Device Name:

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

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

Proprietary / Trade Name: UniCel Dx1 800 Access 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 Product Code: JJE

SEP 2 5 2013

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Predicate Device:

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

The UniCel Dx1 800 Access Immunoassay System claims substantial equivalence to the UniCel DxI 800 Access Immunoassay System (K023764), cleared January 28, 2003.

Device Description:

The Access AccuTnl+3 Reagent packs contain specific reagents for the in virro diagnostic measurement of cTnl including:

· Paramagnetic particles coated with mouse monoclonal anti-human cardiac troponin I (cTnl) 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:

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Comparison to the Predicate:

The Access AccuTnl+3 Reagent and Access AccuTnl+3 Calibrators for use on the UniCel DxI Access Immunoassay Systems and the predicate device, ADVIA Centaur® TnI-Ultra™Assay and ADVIA Centaur TnI-Ultra Calibrators, were compared. The information for the predicate device was derived from the predicate device 510(k) Summary and product labeling.

Characteristic	Predicate DeviceADVIA Centaur® TnI-Ultra™K053020	New DeviceAccess AccuTnI+3
Intended Use	An in vitro diagnostic method for thequantitative measurement of cardiac TnIin 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 in asingle reagent pack	same
Primary ReagentMaterials	Solid phase magnetic particles, anti- cTnIantibodies	same

Similarities between the Access AccuTn1+3 Reagent and Calibrator and the Predicate

Differences between the Access AccuTn1+3 Reagent and Calibrator and the Predicate

Characteristic	Predicate DeviceADVIA Centaur® TnI-Ultra™K053020	New DeviceAccess AccuTnl+3
Sample Type	EDTA plasma	No EDTA plasma claim
ImmunoassayInstrument	ADVIA Centaur	UniCel Dxl Immunoassay System
CalibratorMaterials	Bovine cTnI in goat serum	Recombinant troponin complex in bufferedBSA
Calibrators:number andtype	Two Lyophilized : high and low (use withMaster Curve)	Six Liquid: 0 and approximately 0.2, 0.9,3.7, 20 and 80 ng/mL with no master curve
SpecificReagentMaterials	Polyclonal goat anti-cTnl antibody labeledwith acridinium ester, 2 biotinylated mousemonoclonal anti-cTnI antibodies, magneticparticles conjugated with streptavidin	Mouse monoclonal anti-human cTnlalkaline phosphatase conjugate, magneticparticles coated with mouse monoclonalanti-human cTnl
Indications forUse	Cardiac troponin I determinations aid in thediagnosis of acute myocardial infarction andin the risk stratification of patients with non-ST segment elevation acute coronarysyndromes with respective to relative riskmortality, myocardial infarction or increasedprobability of ischemic events requiringurgent revascularization procedures.	No risk stratification indication

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Characteristic	Predicate DeviceADVIA Centaur® TnI-Ultra™K053020	New DeviceAccess AccuTnI+3
SampleVolume	100μL	55μL
AnalyticalMeasuringRange	0.008 ng/mL to 50 ng/mL	0.03 ng/mL to 80 ng/mL
AcuteMyocardialInfarction(AMI) Cutoff	0.78 ng/mL per WHO-defined cutoff	0.03 ng/mL based on clinical trial outcome
ExpectedResults (UpperReferenceLimit)	99th percentile of 0.04 ng/mL; range of 0.02-0.06 ng/mL	99th percentile upper reference limit(URL) is < 0.03 ng/mL with a 97.5% upperconfidence limit of 0.04 ng/mL
Precision	Total CV of 10% at a level of 0.03 ng/mL	Total CV of ≤8% at concentrations >0.075ng/mL. SD ≤0.006 at concentrations≤0.075 ng/mL

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

The UniCel Dxl 800 Access Immunoassay System and the previously cleared version of the UniCel Dx1 800 Access Immunoassay System were compared.

Characteristic	Predicate DeviceUniCel Dx1 800 AccessImmunoassay SystemK023764	New DeviceUniCel DxI 800 AccessImmunoassay System
Indications for Use	The UniCel Dxl 800 AccessImmunoassay System is an in vitrodiagnostic device used for thequantitative, semi-quantitative, orqualitative determination of variousanalyte concentrations found inhuman body fluids.	same
Operating Principle	Micro computer controlled, randomand continuous access	same
Assay Type	Enzyme immunoassays	same
Detection	Chemiluminescent	same
Modules	SPU, sample/reagent storage,pipettor, bulk feeder, analytical,carriage, substrate, pick and place,fluidics, electronic/systemscomputer, peripheral	same

ﺮ

は

Similarities between the UniCel DxI 800 Access Immunoassay System and the Predicate

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Differences between the UniCel DxI 800 Access Immunoassay System and the Predicate
Characteristic	Predicate DeviceUniCel DxI 800 AccessImmunoassay SystemK023764	New DeviceUniCel DxI 800 AccessImmunoassay System
Thermal algorithmcapability	Not present	Present
Assay ProtocolFile (APF)	AccuTnl APF	AccuTnI+3 APF with addition of thethermal algorithm
Software	Version 2.4-4.4	Version 4.5: added capability to implementthe thermal algorithm; added resultsuppression when instrument internal casetemperature is outside 18° to 36°C
OperatingTemperature	18°C to 32°C ambient	18°C to 30°C ambient18°C to 36°C instrument case temperature

Conclusion: The information provided above demonstrates that the new device, the Access AccuTn1+3 Reagent and Access AccuTnl+3 Calibrators for use on the UniCel DxI Access Immunoassay System, have the same intended use as the predicate device. The UniCel Dx1 800 Access Immunoassay System 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 UniCel Dx1 Access 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 is a staff with two snakes entwined around it, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular pattern around the symbol. The logo is black and white.

Public Health Service

Food and Drug Administratio 0903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

September 25, 2013

Beckman Coulter Inc. c/o Kerrie Oetter 1000 Lake Hazeltine Dr. CHASKA MN 55318-1084

Re: K121790

Trade/Device Name: Access AccuTnl+3 Reagent, Access AccuTnI+3 Calibrator, UniCel 1 Dx1 800 Access Immunoassay System

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: September 04, 2013 Received: September 11, 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: 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 Parts 801 and 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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Page 2-Ms. Oetter

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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. 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.hum.

Sincerely yours,

Carol C. Benson -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 Form

510(k) Number (if known): K121790

Device Name: Access AccuTnl+3 Reagent, Access AccuTnl+3 Calibrator and UniCel Dxl 800 Access Immunoassay Systems

Indications for Use:

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 UniCel Dxl Access Immunoassay Systems 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 1 (cTnl) levels in human serum and plasma using the UniCel Dxl Access Immunoassay Systems to aid in the diagnosis of myocardial infarction.

The UniCel Dxl 800 Access 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.

Prescription Use × (Part 21 CFR 801 Subpart D)

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

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

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

Ruth A. Chesler -S

Division Sign-Off Office of In Vitro Devices and Radiologic Health Evaluation and Safety 510(k)k)____________________________________________________________________________________________________________________________________________________________________

Page 1 of 1

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.