For use in the calibration of the Vitros Immunodiagnostic System for the quantitative measurement of cardiac Troponin I (cTnI) in human heparin plasma.

Device Description

The Vitros Troponin I assay is performed using the Vitros Troponin I Reagent Pack and Vitros Immunodiagnostic Products Troponin I Calibrators on the Vitros ECi Immunodiagnostic System with Intellicheck ™ . An immunometric technique is used. Cardiac Troponin I present in the sample reacts simultaneously with a biotinylated antibody (mouse monoclonal anti-cTnI) and a horseradish peroxidase (HRP)-labeled antibody conjugate (affinity purified goat polyclonal anti-cTnI). The antigen-antibody complex is captured by streptavidin on the wells. Unbound materials are removed by washing. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent (a substituted acetanilide) is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent increases the level and duration of the light produced. The light signals are read by the Vitros ECi System. The amount of HRP conjugate bound is directly proportional to the concentration of cTnI present in the sample.

AI/ML Overview

The provided text details a 510(k) submission for the VITROS Immunodiagnostic Products Troponin I Reagent Pack and VITROS Immunodiagnostic Products Troponin I Calibrators. This document primarily focuses on demonstrating substantial equivalence to a predicate device and presenting performance data related to interference and precision rather than explicitly outlining "acceptance criteria" for a novel device's performance against clinical endpoints.

However, based on the provided information, we can infer some performance expectations and how they are addressed:

1. Table of Acceptance Criteria (Inferred) and Reported Device Performance

Since this is a 510(k) submission for an in-vitro diagnostic device, the "acceptance criteria" are implicitly tied to demonstrating performance that is equivalent to a legally marketed predicate device and within clinically acceptable ranges for intended use. The document provides data on precision at relevant Troponin I concentrations and potential interference.

Criteria (Inferred from clinical relevance and typical IVD requirements)	Acceptance Criteria (Implicit/Inferred)	Reported Device Performance
Precision at Upper Reference Limit (0.08 ng/mL)	Acceptable Coefficient of Variation (CV%) and Standard Deviation (SD)	SD: 0.010 ng/mL, CV%: 12.0%
Precision at Lowest Concentration with 10% CV	Achieve 10% CV at a clinically relevant low concentration	Achieve 10% CV at 0.12 ng/mL (SD: 0.012 ng/mL)
Precision at AMI Cutoff (0.4 ng/mL)	Acceptable CV% and SD at the clinical cutoff for Myocardial Infarction	SD: 0.024 ng/mL, CV%: 5.9%
Hemoglobin Interference (at 0.026 ng/mL cTnI)	Bias within acceptable limits at various hemoglobin concentrations	At 100 mg/dL: 0.043 ng/mL positive bias At 250 mg/dL: 0.175 ng/mL positive bias At 500 mg/dL: 0.226 ng/mL positive bias
Hemoglobin Interference (at ~0.3 ng/mL cTnI)	Bias within acceptable limits at various hemoglobin concentrations	At 100 mg/dL: 0.029 ng/mL positive bias (for 0.279 ng/mL cTnI) At 250 mg/dL: 0.075 ng/mL positive bias (for 0.305 ng/mL cTnI) At 500 mg/dL: 0.166 ng/mL positive bias (for 0.347 ng/mL cTnI)
Substantial Equivalence	Demonstrated equivalence to the DADE Dimension™ RxL Cardiac Troponin-I (TROP) Method (K973650)	The submission explicitly states the device is "substantially equivalent" and provides additional interference and precision data to support this conclusion.

The study details that evaluate these performance characteristics are described below:

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

Precision Study:
- Sample Size: Ten patient sample pools.
- Testing Protocol: Assayed in singleton once per day on 11 different days over a 28-day period using a single reagent lot.
- Data Provenance: Not explicitly stated (e.g., country of origin). The samples are referred to as "patient sample pools," suggesting human biological samples. The study design (multiple days, single reagent lot) is typical for prospective precision studies. Retrospective vs. Prospective is not explicitly mentioned but implies prospective testing.
Hemoglobin Interference Study:
- Sample Size: Not explicitly stated, but measurements were performed at two different "troponin levels" (0.026 ng/mL and approximately 0.3 ng/mL) with varying hemoglobin concentrations.
- Testing Protocol: Replicate determinations were performed using one or two different lots of reagent.
- Data Provenance: Not explicitly stated (e.g., country of origin). The nature implies laboratory testing rather than real-world patient data (prospective testing for interference).

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

Not applicable. This is an in-vitro diagnostic (IVD) assay for measuring a biomarker, not an imaging device or a device requiring expert interpretation of results to establish a "ground truth" for the device's output. The "ground truth" for the precision and interference studies would be the known concentration of Troponin I in the spiked samples or the analytical value against which bias is calculated.

4. Adjudication Method for the Test Set

Not applicable. This is an IVD assay, and the outcome is a quantitative measurement, not a subjective interpretation requiring adjudication.

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. This is an IVD assay and does not involve "human readers" or "AI assistance" in the context of interpretation that would necessitate an MRMC study.

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

This is an IVD device, which by its nature, operates in a "standalone" fashion by performing the quantitative measurement. The results are then interpreted by clinicians. The precision and interference studies demonstrate this standalone performance.

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

The "ground truth" for the performance studies is based on:

Known (nominal) concentrations: For the precision and interference studies, the analyte concentrations (Troponin I and hemoglobin) in the samples or spiked samples serve as the reference or nominal "ground truth" against which the device's measurements, variability, and bias are evaluated.
Analytical methods/reference materials: The accuracy of these known concentrations would be established using validated analytical methods and potentially reference materials, though the specific methods for establishing the initial sample concentrations are not detailed in this summary.

8. The Sample Size for the Training Set

Not applicable. This device is a biochemical immunoassay, not a machine learning or AI-driven device that requires a "training set" in the computational sense. Its performance is based on chemical reactions and optical detection.

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

Not applicable, as there is no training set for this type of device.

Summary

{0}------------------------------------------------

K031031

GENERAL INFORMATION 1.0

1.1 510(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 ________________________________________________________________________________________________________________________________________________

1.1.1. Submitter Name, Address, Contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 (585) 453-4152

Ann M Quinn Contact Person:

1.1.2. Preparation Date

Date 510(k) prepared: March 31, 2003

1.1.3. Device Name

Trade or Proprietary Name: VITROS Immunodiagnostic Products Troponin I Reagent Pack VITROS Immunodiagnostic Products Troponin I Calibrators

Common Name: TROPONIN I assay Classification Name: Troponin I (cTnI) Test System

1.1.4. Predicate Device

The VITROS Immunodiagnostic Products Troponin I Reagent Pack and VITROS Immunodiagnostic Products Troponin I Calibrators are substantially equivalent to the DADE Dimension™ RxL Cardiac Troponin-I (TROP) Method.

{1}------------------------------------------------

1.1.5. Device Description

1.1.6. Device Intended Use

The Vitros Troponin I assay is intended for the in vitro quantitative measurement of Troponin I (cTnI) in human heparin plasma to aid in the diagnosis of myocardial infarction.

1.1.7. Comparison to Predicate Device

The Vitros Immunodiagnostic Products Troponin I Reagent Pack and Vitros Immunodiagnostic Products Troponin I Calibrators are substantially equivalent to the DADE Dimension RxL Cardiac Troponin-I (TROP) Method, which was cleared by the FDA (K973650) for IVD use.

Additional data is being provided on hemoglobin interference and precision. A summary of this data is provided in the tables on the following pages.

{2}------------------------------------------------

Hemoglobin may interfere with the Vitros Troponin I assay. At a troponin level of 0.026 ng/mL, hemoglobin at 100, 250, and 500 mg/dL caused a positive bias of 0.043, 0.175 and 0.226 ng/mL respectively. At a troponin level of approximately 0.3 ng/mL, hemoglobin at 100, 250 and 500 mg/dL caused a positive bias of 0.029. 0.075 and 0.166 ng/mL respectively.

				Units = ng/mL (µg/L)
Interferent	Interferent Concentration		AnalyteConc.*	Bias**
Hemoglobin	0.062 mmol/L	100 mg/dL	0.026	0.043
Hemoglobin	0.155 mmol/L	250 mg/dL	0.026	0.175
Hemoglobin	0.310 mmol/L	500 mg/dL	0.026	0.226
Hemoglobin	0.062 mmol/L	100 mg/dL	0.279	0.029
Hemoglobin	0.155 mmol/L	250 mg/dL	0.305	0.075
Hemoglobin	0.310 mmol/L	500 mg/dL	0.347	0.166

Average test concentration of replicate determinations using one or two different lots of reagent.

Estimate of the average difference observed

Precision at low Troponin I concentrations was evaluated to describe performance at Troponin I concentrations equal to, and below the AMI cutoff of 0.4 ng/mL (µg/L). Ten patient sample pools were assayed in singleton once per day on 11 different days over a 28 day period using a single reagent lot. Calibration was performed at the initiation of the data collection period. The precision profile was constructed using all of the pools above the analytical sensitivity. The data presented are provided as a guideline.

The SD observed at the URL of 0.08 ng/mL (ug/L) and at the AMI Cutoff of 0.4 ng/mL (µg/L) were 0.010 (12.0 %CV) and 0.024 (5.9% CV) ng/mL (ug/L), respectively. The lowest concentration at which the VITROS Troponin I assay achieved a 10% CV was 0.12 ng/mL (ug/L).

	Units = ng/mL (µg/L)
	cTnl	Inter-assay Precision
	ng/mL	SD	CV%
Upper Reference Limit (URL)	0.08	0.010	12.0
Lowest Concentration with 10% CV	0.12	0.012	10.0
AMI Cutoff	0.40	0.024	5.9

1.1.8 Conclusions

These additions provide data that continue to support the safe and effective use of the Vitros Troponin I Reagent Pack and Calibrators for use in quantitatively measuring Troponin I concentration in heparin plasma.

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image is a black and white circular logo. The logo features a stylized depiction of an eagle or bird in flight, with three curved lines representing its wings and body. The bird is facing to the right. Encircling the bird is text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES".

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

SEP 2 9 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Ann M. Quinn, RAC Manager, Regulatory Affairs Ortho Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, NY 14626-5101

Re: K031031

Trade/Device Name: Vitros Immunodiagnostic Products Troponin I Reagent Pack Vitros Immunodiagnostic Products Troponin I Calibrators Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI; JIT Dated: September 4, 2003 Received: September 5, 2003

Dear Ms Quinn .:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{4}------------------------------------------------

Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{5}------------------------------------------------

Statement of Intended Use 1.2

Page 1 of 1

510(k) Number (if known):

Device Name:

VITROS Immunodiagnostic Products Troponin I Reagent Pack

VITROS Immunodiagnostic Products Troponin I Calibrators

Indications for Use:

For the in vitro quantitative measurement of Troponin I (cTnI) in human heparin plasma to aid in the diagnosis of myocardial infarction.

For use in the calibration of the Vitros Immunodiagnostic System for the quantitative measurement of cardiac Troponin I (cTnI) in human heparin plasma.

Stean Lopez
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K631031

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use __

(Optional Format 1-2-96)

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.