The CTNI method is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I in human serum and plasma on the Dimension Vista™ System. Measurements of cardiac troponin I are used to aid in the diagnosis of acute myocardial infarction (AMI) and in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality.

Device Description

The CTNI method is a one-step sandwich chemiluminescent immunoassay based on LOCI™ technology. LOCI™ reagents include two synthetic bead reagents and a biotinylated anti-cardiac troponin I monoclonal antibody fragment. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. The second bead reagent (Chemibeads) is coated with a second anti-cardiac troponin I monoclonal antibody and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibody to form a particle/cardiac troponin I/biotinylated antibody sandwich. Sensibeads then are added and bind to the biotin to form bead-aggregated immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from Sensibeads, which diffuses into the Chemibeads and triggers a chemiluminescent reaction. The resulting chemiluminescent signal is measured at 612 nm and is a direct function of the cardiac troponin I concentration in the sample.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting studies for the Dimension Vista™ CTNI Flex® reagent cartridge, structured according to your request:

1. Table of Acceptance Criteria and Reported Device Performance

The submission doesn't explicitly define 'acceptance criteria' in a dedicated section with pass/fail thresholds. Instead, it presents performance characteristics and demonstrates substantial equivalence to a predicate device. The implied acceptance is that the new device's performance is comparable to or improved upon the predicate.

Feature	Predicate Device Performance (Dimension® CTNI)	New Device Performance (Dimension Vista™ CTNI)	Implied Acceptance Criteria (relative to predicate)	Met Criteria?
Intended Use	Quantitative determination of cardiac troponin-I in human serum and heparinized plasma for AMI diagnosis and risk stratification in ACS.	Identical.	Identical intended use.	Yes
Assay Type	Photometric immunoassay	Chemiluminescent immunoassay	New technology is acceptable if other performance is comparable or better.	Yes
Reportable Range	0.04 to 40 ng/mL	0.015 to 40 ng/mL	Equal or wider (especially lower) range.	Yes (improved)
Analytical Sensitivity	0.04 ng/mL	0.015 ng/mL	Equal or better (lower) sensitivity.	Yes (improved)
Functional Sensitivity	Not specified	0.04 ng/mL	Functional sensitivity in line with clinical needs (not directly comparable to predicate's unspecified value, but a specified value is a positive).	Yes
Analytical Specificity (Skeletal muscle troponin-I)	0.04 ng/mL (at 1000 ng/mL)	0.14 ng/mL (at 1000 ng/mL)	Comparable specificity.	Yes
Analytical Specificity (Cardiac troponin-T)	0.34 ng/mL (at 1000 ng/mL)	0.05 ng/mL (at 1000 ng/mL)	Comparable or better specificity.	Yes (improved)
Analytical Specificity (Cardiac troponin-C)	0 ng/mL (at 1000 ng/mL)	0 ng/mL (at 1000 ng/mL)	Identical specificity.	Yes
Hook Effect	No high dose effect up to 1800 ng/mL	No high dose effect up to 1000 ng/mL	No hook effect within a relevant clinical range. (Slightly narrower range than predicate but still clinically acceptable).	Yes
Calibration Interval	Updated for each lot, 5 levels, every 60 days.	Updated for each lot, 6 levels, every 30 days.	Updated for each lot with appropriate frequency and levels. (More frequent calibration and more levels could be seen as an improvement in control).	Yes
Sample Volume	50 µL	20 µL	Equal or smaller sample volume.	Yes (improved)
Method Comparison (Slope)	N/A (Predicate vs. itself)	0.99	Close to 1.0 (indicating good agreement).	Yes
Method Comparison (Intercept)	N/A	-0.10	Close to 0 (indicating good agreement).	Yes
Method Comparison (Correlation Coefficient)	N/A	0.993	High (indicating strong linear correlation).	Yes
Serum vs. Plasma (Slope)	N/A	1.02	Close to 1.0 (indicating good agreement).	Yes
Serum vs. Plasma (Intercept)	N/A	0.031	Close to 0 (indicating good agreement).	Yes
Serum vs. Plasma (Correlation Coefficient)	N/A	0.999	High (indicating strong linear correlation).	Yes
Li Heparin vs. Na Heparin (Slope)	N/A	0.99	Close to 1.0 (indicating good agreement).	Yes
Li Heparin vs. Na Heparin (Intercept)	N/A	-0.05	Close to 0 (indicating good agreement).	Yes
Li Heparin vs. Na Heparin (Correlation Coefficient)	N/A	0.998	High (indicating strong linear correlation).	Yes
Reproducibility (Repeatability %CV)	Not explicitly compared with predicate as a criterion.	Low %CVs (3.8%, 1.25%, 1.05%, 1.0%, 1.7%)	Low %CVs demonstrate good precision. (Acceptance is usually based on pre-defined internal company limits or industry standards for similar assays).	Yes
Reproducibility (Within Lab %CV)	Not explicitly compared with predicate as a criterion.	Low %CVs (7.36%, 3.18%, 2.22%, 3.76%, 1.05%)	Low %CVs demonstrate good precision.	Yes

2. Sample Sizes and Data Provenance

Method Comparison (Test Set for predicate comparison):
- Sample Size: 91 split serum patient samples.
- Data Provenance: Not explicitly stated, but implied to be human patient samples. The country of origin is not mentioned. It is retrospective since existing patient samples were used to compare two methods.
Serum versus Plasma Results:
- Sample Size: 63 matched serum and lithium heparin plasma samples.
- Data Provenance: Not explicitly stated (country of origin), implied to be human patient samples. Retrospective.
Lithium Heparin versus Sodium Heparin Results:
- Sample Size: 50 matched lithium and sodium heparin plasma samples.
- Data Provenance: Not explicitly stated (country of origin), implied to be human patient samples. Retrospective.
Reproducibility (Test Set for precision):
- Sample Size: 4 serum pools and 1 Biorad Cardiac Quality Control, Level 2. The number of runs/replicates per sample is specified: "a single test from two independent cups was analyzed twice per day." The total number of individual measurements is not directly provided but can be inferred from the GLSI document referenced.
- Data Provenance: Not explicitly stated (country of origin). Implied to be in-house laboratory testing. Not directly patient samples for this part, but control materials.

3. Number of Experts and Qualifications for Ground Truth

Not applicable. This submission is for an in vitro diagnostic (IVD) test measuring a biomarker (cardiac troponin I). The "ground truth" for method comparison and precision studies is the measurement itself, typically compared against a reference method (the predicate device in this case) or internal controls with known values. There are no human expert adjudicators involved in establishing ground truth for IVD performance characteristics like analytical sensitivity, range, precision, or method correlation.

4. Adjudication Method for the Test Set

Not applicable. As described above, there's no human adjudication for establishing ground truth in these types of analytical performance studies for IVD devices. The comparison is statistical between the two methods' results.

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

No. This is an IVD device, specifically a lab assay. MRMC studies are typically used for imaging devices or other diagnostic systems where human readers interpret output and their performance (with/without AI assistance) is evaluated. This submission focuses on the analytical performance of the assay itself, not human interpretation of results.

6. Standalone (Algorithm Only) Performance Study

Yes, implicitly. The entire submission describes the "standalone" performance of the Dimension Vista™ CTNI Flex® reagent cartridge system. This device is an automated immunoassay, meaning the algorithm/system produces a quantitative result without direct human intervention in the measurement process itself. The data presented reflects the performance of the algorithm and instrumentation together. It's a "device only" performance inherent in IVD submissions.

7. Type of Ground Truth Used

For Method Comparison Studies: The ground truth for the comparison was established by the predicate device (Dade Behring Dimension® CTNI method). The study aims to show good agreement between the new device's results and the predicate's results when testing the same patient samples.
For Reproducibility Studies: The ground truth for reproducibility is the mean concentration of the control materials/patient pools, established through repeated measurements. The goal is to demonstrate consistency and precision around this mean.
For Specificity Studies: The ground truth is the known concentration of interfering substances (skeletal muscle troponin-I, cardiac troponin-T, cardiac troponin-C) in spiked samples, to see if they cross-react with the assay.

8. Sample Size for the Training Set

Training Set Sample Size: Not specified in the provided text. IVD submissions typically focus on validation studies (test sets) rather than detailing the internal development/training an assay might undergo. For an immunoassay, "training" might refer to assay development, optimization of reagents, and initial performance characterization, rather than a distinct "training set" in the machine learning sense.

9. How Ground Truth for the Training Set Was Established

Not explicitly stated/applicable in the same way as AI/ML. For an IVD immunoassay, the "ground truth" during development involves using reference materials, characterized samples, and known concentrations of analytes and interferents to optimize the assay's chemical and enzymatic reactions, antibody binding, and signal detection to accurately measure the target analyte (cardiac troponin I). This iterative process involves internal laboratory testing and characterization rather than an external "ground truth establishment" phase for a discrete "training set."

Summary

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

K063756

510(K) SUMMARY OF SAFETY AND EFFECTIVENESS INFORMATION

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.

Submitter's Name:	George M. PlummerDade Behring Inc.P.O. Box 6101Newark, DE 19714-6101	MAR 1 9 200
Date of Preparation:	December 18, 2006
Name of Product(s):	Dimension Vista™ CTNI Flex® reagent cartridge
FDA Classification Name(s):	Immunoassay method, Troponin subunit (862.1215)
FDA Guidance Documents:	None applicable
Predicate Device(s):	Dade Behring Dimension® CTNI immunoassay (K0101313)

Device Description(s):

Intended Use:

The CTNI method is an in vitro diagnostic test for the quantitative measurement of cardiac troponin 1 in human serum and plasma on the Dimension Vista® System. Measurements of cardiac troponin I are used to aid in the diagnosis of acute myocardial infarction (AMI) and in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality.

Substantial Equivalence

A summary of the performance attributes of the Dade Behring Dimension Vista™ CTNI Flex® reagent cartridge and the predicate Dade Behring Dimension® CTNI reagent cartridge immunoassay (K0101313) is provided in the following chart.

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

Feature	Dimension® CTNI	Revised Dimension Vista™ CTNI
Intended Use	For the in vitro quantitativedetermination of cardiactroponin -I in human serum andheparinized plasma as an aid inthe diagnosis of myocardialinfarction and in the riskstratification of patients withacute coronary syndromes withrespect to their relative risk ofmortality.	For the in vitro quantitativedetermination of cardiac troponin -I inhuman serum and heparinized plasmaas an aid in the diagnosis of myocardiainfarction and in the risk stratificationof patients with acute coronarysyndromes with respect to their relativrisk of mortality.
Assay Type	photometric immunoassay	chemiluminescent immunoassay
Reportable Range	0.04 to 40 ng/mL	0.015 to 40 ng/mL
Antibody	Dade Behring mousemonoclonal	Dade Behring mouse monoclonal
Analytical Sensitivity	0.04 ng/mL	0.015 ng/mL
FunctionalSensitivity	Not specified	0.04 ng/mL
Analytical Specificity	Cross reactivity at 1000 ng/mLwith skeletal muscle troponin-I,cardiac troponin -T and cardiactroponin-C is 0.04 ng/mL, 0.34ng/mL and 0 ng/mLrespectively.	Cross reactivity at 1000 ng/mL withskeletal muscle troponin-I, cardiactroponin --T and cardiac troponin-C is0.14 ng/mL, 0.05 ng/mL and 0 ng/mLrespectively.
Hook Effect	No high dose effectup to 1800 ng/mL	No high dose effect up to 1000 ng/mL
Calibration Interval	Calibration curve updated foreach lot, using five levels andevery 60 days, thereafter withthe same reagent lot.	Calibration curve updated for each lot,using six levels every 30 days with thesame reagent lot.
Sample Volume	50 µL	20 µL

and the comments of the comments of

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

Method performance Summary:

Analytical Results

Method Comparison

A split, serum patient sample method comparison demonstrated good agreement between the revised Dade Behring Dimension Vista™ CTNI method and the predicate Dade Behring Dimension® CTNI method.

Dimension®SampleRange	DimensionVista® SampleRange	n	Slope	Intercept	CorrelationCoefficient
0-35.34	0.13 - 38.85	91	0.99	-0.10	0.993

The model equation for the linear least squares regression statistics is: [results for revised Dimension Vista™ CTNI] = slope x [comparative method results] + intercept.

Serum versus Plasma Results

Comparison of sixty-three matched serum and lithium heparin plasma samples were tested with the revised Dimension Vista™ CTNI method. The following table summarizes the linear least squares regression from the study.

Plasma SampleRange	Serum SampleRange	n	Slope	Intercept	CorrelationCoefficient
0.026-23.7	0.026-22.9	63	1.02	0.031	0.999

Lithium Heparin versus Sodium Heparin Results

Comparison of 50 matched lithium and sodium heparin plasma samples were tested with the revised Dimension Vista™ CTNI method. The following table summarizes the linear least squares regression results from the study.

Li HeparinSample Range	Na HeparinSample Range	n	Slope	Intercept	CorrelationCoefficient
0.09 - 39.85	0.1 - 38.2	50	0.99	-0.05	0.998

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

Reproducibilitv

Typical precision observed for the Dimension Vista™ CTNI method is summarized below:

		Repeatability		Within Lab
Sample	Mean (ng/mL)	SD (ng/mL)	%CV	SD (ng/mL)	%CV
Serum Pool 1	0.073	0.003	3.8	0.005	7.36
Serum Pool 2	0.43	0.005	1.25	0.014	3.18
Serum Pool 3	22.5	0.237	1.05	0.499	2.22
Serum Pool 4	30.55	0.310	1.0	0.975	3.76
Biorad CardiacQuality Control,Level 2	0.51	0.009	1.7	0.005	1.05

The reproducibility testing was conducted in accordance with the CLSI Approved Guideline for User Evaluation of Precision Performance of Clinical Chemistry Devices EPS-A2. For each test level, a single test from two independent cups was analyzed twice per day. The repeatability and within-lab standard deviations were calculated by the analysis of variance method.

Comments on Substantial Equivalence:

Both the predicate Dimension® CTNI reagent cartridge and the revised Dimension Vista™ CTNI immunoassays are intended for the quantitative determination of troponin I. Comparative data for human serum and heparinized plasma samples demonstrate good analytical agreement between the methods.

Conclusion:

The Dade Behring revised Dimension Vista™ CTNI and the predicate Dade Behring Dimension® CTNI immunoassays (K0101313) are substantially equivalent based on their intended use and performance characteristics as described above.

George M. Plummer Regulatory Affairs and Compliance Manager December 18, 2006

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wings. The eagle faces right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Dade Behring, Inc. c/o George M. Plummer Bldg. 500 Mail Box 514 P.O. Box 6101 Newark, DE 19714-6101

MAR 1 9 2007

Re: K063756

Trade/Device Name: Dimension VISTA™ CTNI Flex® reagent cartridge Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system. Regulatory Class: Class II Product Code: MMI Dated: December 18, 2006 Received: December 19, 2006

Dear Mr. Plummer:

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).

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

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 (240) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Jean M. Cooper, M.S., D.V.M.

Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{6}------------------------------------------------

INDICATIONS FOR USE STATEMENT

510(k) Number (If Known):

X063756

Device(s) Name(s):

Dimension Vista™ CTNI Flex® reagent cartridge

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D) and/or

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 Diagnostic Devices (OIVD)

Carol Benson

ision Sign-Off

ffice of In Vitro Diagnostic Device valuation and Safety

K063756

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.