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

Device Description

The Access hsTnl assay is a sandwich immunoenzymatic assay. The Access hsTnl assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access hsTnl reagent pack, Access hsTnl calibrators, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.

AI/ML Overview

The provided text describes the Beckman Coulter Access hsTnI device, a chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) to aid in the diagnosis of myocardial infarction (MI). The information below summarizes the acceptance criteria and the study used to prove the device meets these criteria.

1. A table of acceptance criteria and the reported device performance

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Clinical Performance (Method Comparison)	Slope 1.00 ± 0.10 (compared to predicate)	Met, supporting equivalence of Access hsTnI on Dxl 9000 to Access hsTnI on Dxl 9000 Access Immunoassay Analyzer for plasma and serum samples.
Imprecision	≤ 10% within-laboratory CV for concentrations ≥ 11.5 pg/mL; ≤ 1.15 pg/mL within-laboratory SD for concentrations < 11.5 pg/mL	Serum: 2.3% to 6.4% for concentrations ≥ 11.5 pg/mL; 0.17 to 0.33 SD for concentrations < 11.5 pg/mL. Plasma: 1.7% to 4.4% for concentrations ≥ 11.5 pg/mL; 0.17 to 0.40 SD for concentrations < 11.5 pg/mL.
Linearity (Non-linearity)	Within ± 10% for values ≥ 11.5 pg/mL; Within ± 1.15 pg/mL for values < 11.5 pg/mL	Met
Limit of Blank (LoB)	Not explicitly stated, but implies a low value acceptable	0.5 pg/mL
Limit of Detection (LoD)	Not explicitly stated, but implies a low value acceptable	Serum: 0.9 pg/mL Plasma: 0.8 pg/mL
Limit of Quantitation (LoQ) at ≤20% within-lab CV	≤ 20% within-lab CV	Serum: 1.0 pg/mL Plasma: 0.8 pg/mL
Carryover	Unspecified, but implies minimal effect on low samples	No clinically significant carryover for ≥95% of high samples tested (up to 270,000 pg/mL), based on a concentration shift of <3.5 pg/mL when testing a low sample (≤10 pg/mL).

2. Sample size used for the test set and the data provenance

The document does not specify the exact sample sizes used for the clinical performance (method comparison), imprecision, linearity, LoB/LoD, LoQ, or carryover studies.
The provenance of the data (e.g., country of origin, retrospective or prospective) is not explicitly stated.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable. This device is an immunoassay for quantitative determination of a biomarker, not a diagnostic imaging or AI-assisted diagnostic tool that requires expert human interpretation for ground truth establishment in the traditional sense. The ground truth for this type of device is typically established through biochemical analysis and reference methods, not expert consensus on image interpretation or clinical diagnosis.

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

Not applicable for this type of immunoassay device. Adjudication methods like 2+1 or 3+1 are typically used in studies where human experts interpret results (e.g., medical images) and their decisions need to be arbitrated.

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

Not applicable. The Access hsTnI device is a standalone in-vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers. Therefore, an MRMC study assessing human reader improvement with AI assistance would not be conducted for this device.

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

Yes, the studies described (clinical performance, imprecision, linearity, LoB/LoD, LoQ, carryover) represent standalone performance evaluations of the assay system without human-in-the-loop performance being a primary evaluation criterion. The device itself provides a quantitative result.

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

For an immunoassay like Access hsTnI, the ground truth is established by:

Reference Methods: Comparison to established and accepted laboratory methods for measuring cTnI, typically the predicate device (Access hsTnI on Access 2 Immunoassay System) as indicated in the method comparison study.
Analytical Standards: Use of precisely characterized control materials and calibrators with known concentrations of cTnI to assess accuracy, linearity, and limits of detection/quantification.

8. The sample size for the training set

Not applicable in the context of machine learning model training. This is an immunoassay, not an AI/ML device that requires a training set in that sense. The "training" for such a device involves iterative development and validation using various samples to define its analytical characteristics.

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

Not applicable as it's not an AI/ML device with a distinct "training set" in the machine learning paradigm. The development and optimization of the immunoassay reagents and protocol would have relied on well-characterized samples with known cTnI concentrations, established through analytical methods and reference standards.

Summary

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December 18, 2023

Beckman Coulter, Inc. Kate Oelberg Senior Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K222881

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: August 3, 2023 Received: August 3, 2023

Dear Kate Oelberg:

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 (the 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Paula V. Caposino -S

Paula Caposino, Ph.D. Acting Deputy Division Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K222881

Device Name Access hsTnI

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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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(a)(1).

The assigned 510(k) number is K222881

Submitted By:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

Contact Person:

Kate Oelberg 1000 Lake Hazeltine Drive Chaska, MN 55318 Phone: (612) 431-7315 Email: kmoelberg@beckman.com

Alternate Contact:

Stephanie Garth Office Phone: (469) 858-1408 Email: SGARTH01@beckman.com

Trade Name: Access hsTnl Common Name: Troponin | Enzyme Immunoassay Classification Requlation: 21 CFR 862.1215 Classification Product Code: MMI

Predicate Devices: Access hsTnl, FDA 510(k) Number K172787

Device Description

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 Dxl Access Immunoassay Analyzers to aid in the diagnosis of myocardial infarction (MI).

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Comparison of Technological Characteristics to the Predicate (Assay)
Characteristic	Predicate Access hsTnl on Access 2 Immunoassay System	Access hsTnl for Dxl 9000 Access Immunoassay Analyzer
Intended Use/ Indications for Use	Access hsTnl is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma using the Access 2 Immunoassay Systems to aid in the diagnosis of myocardial infarction (MI).	Access hsTnl is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnI) levels in human serum and plasma using the Dxl Access Immunoassay Analyzers to aid in the diagnosis of myocardial infarction (MI).
Technology	Sandwich	Same
Format	Chemiluminescent	Same
Method	Automated	Same
Sample Type	Serum and lithium heparin plasma	Same
Analytical Measuring Range	2.0 pg/mL to 27,027 pg/mL	Same
Automated Dilution (Dilution Recovery)	Up to approximately 270,270 pg/mL	Same
Expected Results (Upper Reference Limit)	99th percentile of 17.5 pg/ mL with a 95% Confidence Interval (CI) of 12.6 - 20.7 pg/mL for plasma and 18.2 pg/mL with a 95% Confidence Interval (CI) of 13.1-23.1 pg/mL for serum.	Same
Precision	≤ 10% within-laboratory CV for concentrations ≥ 11.5 pg/mL ≤ 1.15 pg/mL within laboratory SD for concentrations < 11.5 pg/mL	Same
Primary Reagent Materials	Mouse monoclonal anti-human cTnl antibody; detection is Sheep monoclonal anti-human cTnl	Same
Open Reagent Pack Stability	Stable at 2 to 10°C for 64 days after opening	Same
Reagent Pack configuration	Reagents ready to use and separated in a single reagent pack	Same
Assay Protocol File (APF)	hsTnl APF with no thermal algorithm	Same
Immunoassay Instrument	Access 2 Immunoassay system	Dxl 9000 Access Immunoassay Analyzer
Substrate	Access Substrate	Lumi-Phos PRO substrate

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Clinical performance: A study based on CLSI EP09c, 3rd Edition using Passing-Bablok regression and Pearson's correlation compared the Access 2 Immunoassay System and the Dxl 9000 Access Immunoassay Analyzer. The results of the method comparison study met the acceptance criteria of slope 1.00 ± 0.10 and supports the equivalence of the Access hsTnl on Dxl 9000 to the Access hsTnl on Dxl 9000 Access Immunoassay Analyzer for both lithium heparin plasma and serum samples.

lmprecision: The within-laboratory (total) % CV ranged from 2.3% to 6.4% for serum samples and 1.7% to 4.4% for plasma samples, for hsTnl concentrations ≥ 11.5 pg/mL. The withinlaboratory (total) SD ranged from 0.17 to 0.33 for serum samples and 0.17 to 0.40 for plasma samples with hsTnl concentrations < 11.5 pg/mL.

Linearity: This study shows that the acceptance criteria was met for non-linearity within ± 10% for values ≥11.5 pg/mL and ± 1.15 pg/mL for values < 11.5 pg/mL.

LoB/LoD: The data demonstrated the LoB estimate of the Access hsTnl is 0.5 pg/mL and the LoD estimate are 0.9 pg/mL (serum) and 0.8 pg/mL(plasma).

LoQ: The LoQ for Access hsTnl at ≤20% with-in lab CV was determined to be 1.0 pg/mL (serum) and 0.8 pq/mL (plasma).

Carryover: No clinically significant carryover for ≥95% of high samples tested up to 270,000 pg/mL (ng/L), based on a concentration shift of <3.5 pg/mL (ng/L) when testing a low sample (≤10 pg/mL [ng/L]).

Substantial Equivalence Comparison Conclusion

The information provided in this submission supports a substantial equivalence determination. and therefore 510(k) premarket notification clearance of the Access hsTnl on Dxl 9000 Access Immunoassay Analyzer.

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.