Access hsTnI is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin I (cTnl) levels in human serum and plasma using the Access 2 Immunoassay Systems to aid in the diagnosis of myocardial infarction (MI).

Device Description

The Access hsTnI is a two-site immunoenzymatic ("sandwich") assay. Monoclonal anti-cTnl antibody coniugated to alkaline phosphatase is added to a reaction vessel along with a surfactant-containing buffer and sample. After a short incubation, paramagnetic particles coated with monoclonal anti-cTnl antibody are added. The human cTnl binds to the anti-cTnl antibody on the solid phase, while the anti-cTnl antibody-alkaline phosphatase conjugate reacts with different antigenic sites on the cTnl molecules. After incubation, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of analyte in the sample. Analyte concentration is automatically determined from a stored calibration.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Access hsTnI device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Parameter	Acceptance Criteria (Predicate)	Reported Device Performance (Candidate)
Precision	≤ 10% within-laboratory CV for concentrations ≥ 11.5 pg/mL ≤ 1.15 pg/mL within laboratory SD for concentrations < 11.5 pg/mL	Method comparison: Slope 1.00 ± 0.10 (met). Within-lab precision: 3% to 4% CV for concentrations ≥ 11.5 pg/mL; SD of 0.52 pg/mL for concentrations < 11.5 pg/mL.
Analytical Measuring Range	2.0 pg/mL to 27,027 pg/mL	Implicitly met as the Analytical Measuring Range from predicate is stated as "Same".
Linearity	Not explicitly stated as a numerical criterion in the "Predicate" column.	Higher order (2nd or 3rd) term of polynomial fit is non-significant (p > 0.05), or if significant, bias ≤ 10% across the analytical measuring range.
LoB (Limit of Blank)	Not explicitly stated as a numerical criterion in the "Predicate" column.	0.6 pg/mL
LoD (Limit of Detection)	Not explicitly stated as a numerical criterion in the "Predicate" column.	1.0 pg/mL (serum) and 0.6 pg/mL (plasma)
LoQ (Limit of Quantitation)	Not explicitly stated as a numerical criterion in the "Predicate" column.	0.8 pg/mL (serum) and 0.7 pg/mL (plasma) at ≤20% within-lab CV
Carryover	Not explicitly stated as a numerical criterion in the "Predicate" column.	≥ 95% of maximum individual replicate carryover events < 3.5 pg/mL when testing a low sample (≤ 10 pg/mL) following a high sample (~150,000 pg/mL).
Method Comparison (Slope)	Slope 1.00 ± 0.10	1.00 ± 0.10 (met)
Bias	Implicitly met for reference intervals	Bias data support the reference intervals defined on the instruments have not changed appreciably from the commercialized product.

2. Sample Size for the Test Set and Data Provenance

Sample Size:
- Method Comparison: 92 samples (41 Lithium Heparin Plasma and 51 Serum).
- Precision (within-laboratory): Not explicitly stated, but results are given for concentrations ≥ 11.5 pg/mL and < 11.5 pg/mL.
- Linearity: Not explicitly stated how many samples were used, but it mentions "each sample concentration range."
- LoB/LoD/LoQ: Not explicitly stated.
- Carryover: Not explicitly stated.
Data Provenance: Not specified (e.g., country of origin, retrospective or prospective). The samples were "human serum and plasma," suggesting patient samples were collected, but the specific details are not provided in this summary.

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

This device is an in-vitro diagnostic (IVD) immunoassay for the quantitative determination of cardiac troponin I (cTnl). The "ground truth" for such devices is established by the analytical measurement of the analyte itself, not typically by expert consensus of images or clinical assessments in the same way as, for example, an AI diagnostic tool for radiology.

Therefore, the concept of "experts establishing ground truth for the test set" (e.g., radiologists) is not directly applicable here. The "truth" is based on the highly controlled and validated measurements of cTnl concentrations using established laboratory methods.

4. Adjudication Method for the Test Set

Since the ground truth for this type of device is established by analytical measurement rather than subjective interpretation, an adjudication method like 2+1 or 3+1 (common in image-based diagnostic studies) is not applicable. The measurements are taken directly and compared to a reference method or validated analytical ranges.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This type of study is relevant for evaluating the impact of an AI system on human reader performance, especially in image-based diagnostics. The Access hsTnI is a standalone immunoassay directly measuring a biomarker, not an AI-assisted diagnostic tool that aids human interpretation.

6. Standalone Performance (Algorithm Only Without Human-in-the-Loop)

Yes, the studies conducted (precision, linearity, LoB/LoD/LoQ, carryover, method comparison) evaluate the standalone performance of the Access hsTnI device (the immunoassay system itself) without human-in-the-loop interaction for interpretation, other than standard laboratory procedures for running the assay. The device provides a quantitative measurement directly.

7. Type of Ground Truth Used

The ground truth used is analytical measurement of cardiac troponin I (cTnl) concentrations. This is established through highly precise and accurate laboratory methods, often using reference standards and validated instrumentation. For the method comparison, the "IVD Access hsTnl (Current Assay Protocol File (APF))" likely served as the reference or comparative method against the "proposed Access hsTnl (Proposed APF)".

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI. This device is an immunoassay, which typically relies on chemical reactions and signal detection, not a machine learning model that requires a training set. The term "training set" is not applicable in this context. The "calibration" mentioned ("Analyte concentration is automatically determined from a stored calibration") implies a process by which the instrument is set up to accurately measure concentrations, but this is distinct from an AI training set.

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

As noted above, a "training set" in the AI sense is not applicable. For instrument calibration, the ground truth (e.g., known concentrations of cTnl) is established using certified reference materials or highly characterized standards with defined concentrations. These known concentrations are then used to generate a calibration curve that allows the instrument to quantify cTnl in unknown samples.

Summary

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December 4, 2023

Stephanie Garth Principal of Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K230648

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: October 31, 2023 Received: October 31, 2023

Dear Stephanie Garth:

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/cdrb/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) K230648

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 SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is K230648

Submitter Name and Address:

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

Contact Person:

Stephanie Garth, Principal of Regulatory Affairs Phone: (469) 858 -1408 Email: sgarth01@beckman.com

Alternate Contact:

Kuljeet Kaur, RA, Senior Manager Phone: (952) 465 -1914 Email: kkaur@beckman.com

Date Prepared:

March 8, 2023

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

Predicate Devices:

Beckman Coulter, Inc. believes that the Access hsTnl run on the legacy Access 2 Immunoassay System (K172787 - Predicate) is substantially equivalent to the improved Access hsTnl with a software upgrade to assist with washing efficiency. The following table provides a comparison of the technological characteristics of the predicate Access hsTnl on the Access 2 with and without the modifications.

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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 Access 2 Immunoassay Systems to aid in the diagnosis of myocardial infarction (MI).

Characteristic	Access hsTnlK172787 - Predicate	Access hsTnICandidate
Intended Use/Indications forUse	Access hsTnl is a paramagneticparticle, chemiluminescentimmunoassay for the quantitativedetermination of cardiac troponin I(cTnl) levels in human serum andplasma using the Access 2Immunoassay Systems to aid in thediagnosis of myocardial infarction(MI).	Same
Assay Principle	Chemiluminescent	Same
Technology	Sandwich	Same
Test Systems	Automated immunoassay instrument	Same
Sample Type	Serum and lithium heparin plasma	Same
Sample Volume	55µl	Same
Precision	≤ 10% within-laboratory CV forconcentrations ≥ 11.5 pg/mL≤ 1.15 pg/mL within laboratory SD forconcentrations < 11.5 pg/mL	Same
AnalyticalMeasuringRange	2.0 pg/mL to 27,027 pg/mL	Same
Characteristic	Access hsTnlK172787 - Predicate	Access hsTnlCandidate
ExpectedResults (UpperReference Limit)	99th percentile of 17.5 pg/mL with a95% Confidence Interval (CI) of 12.6- 20.7 pg/mL for lithium heparinplasma and 18.2 pg/mL with a 95%Confidence Interval (CI) of 13.1-23.1pg/mL for serum.	Same
PrimaryReagentMaterials	Mouse monoclonal anti-human cTnlantibody; detection is Sheepmonoclonal anti-human cTnl	Same
Open ReagentPack Stability	Stable at 2 to 10°C for 64 days afteropening	Same
Reagent Packconfiguration	Reagents ready to use andseparated in a single reagent pack	Same
Access 2 AssayProtocolFile (APF)	Access hsTnl APF with no thermalalgorithm	Same
General Device Characteristic Differences
System software	In current system softwarearchitecture, RV mix could onlyhappen at the end of the 4th cycle	Proposed system softwarearchitecture, RV mix canbe utilized in any of thecycles
Assay ProtocolFile (APF)	Access 21 probe wash after probes' finalcontact with reaction solutions andRV mix	Access 23 probe washes and 1NAOH exposure afterreagent probe's finalcontact with reactionsolutions and RV mix
Dilutionfactor/recoveryExtendedrecovery range	Dilution Factor of 10	1:5 dilution factor andnew limitationstatement related tocarryover

Substantial Equivalence Comparison:

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Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Third Edition

CLSI EP06-2nd Edition-: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach: Approved Guideline

CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition

CLSI EP09c: Measurement Procedure Comparison and Bias Estimation Using Patient Samples- Third Edition

Method comparison: Ninety two (92) samples (41 Lithium Heparin Plasma and 51 Serum) were analyzed across 2 Access 2 instruments, Each sample was measured using the IVD Access hsTnl (Current Assay Protocol File (APF)) as well as the proposed Access hsTnl (Proposed APF). The first replicate result from each sample was utilized to fit a Passing-Bablok linear regression model. 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 Access 2 for both lithium heparin plasma and serum samples. The bias data support the reference intervals defined on the instruments have not changed appreciably from the commercialized product.

lmprecision: For Access 2 instrument the within-laboratory (total) % CV ranged from 3% to 4%, for Access hsTnl concentrations ≥ 11.5 pg/mL. The withinlaboratory (total) SD was 0.52 pq/mL for Access hsTnl concentration < 11.5 pg/mL.

Linearity: This study shows that the analysis of the data finds that across both platforms, and for each sample concentration range, the higher order (2nd or 3rd) term of the polynomial fit is non-significant (p > 0.05), and if significant, the fit of the polynomial regression demonstrating significance have ≤ 10% bias across the analytical measuring range.

LoB/LoD: The data demonstrated the LoB estimate of the Access hsTnl is 0.6 and the LoD estimate is 1.0 (serum) and 0.6 (plasma).

LoQ: The LoQ for Access hsTnl at ≤20% with-in lab CV was determined to be 0.8 pg/mL (serum) and 0.7 (plasma).

Carryover and new dilution factors: Access 2 demonstrated ≥ 95% of maximum individual replicate carryover events < 3.5 pg/mL when testing a low sample (≤ 10 pg/mL) following a high sample (~150,000 pg/mL).

Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access hsTnl on the Access 2 Immunoassay System is substantially equivalent to Access hsTnl on the predicate as demonstrated through the information and data provided in this submission. The performance testing presented in this submission provides evidence that the device is safe and effective in its intended use.

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.