The TNI method is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I in human serum and plasma on the Dimension® EXL™ integrated chemistry system with LOCI® module. Measurements of cardiac troponin I are used as an 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.

The CTNI Sample Diluent is an in vitro diagnostic product for manual dilution of samples with elevated cardiac troponin I results processed on the Dimension Vista® and Dimension® EXL™ integrated chemistry system with LOCI® module.

Device Description

The Dimension® TNI Flex® reagent cartridge is an in vitro diagnostic device that consists of prepackaged reagents in a plastic eight-well cartridge for use on the Dimension® EXL™ with LM system.

The TNI method is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI® technology. The 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 photosensitizer 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 bead-cardiac troponin I-biotinylated antibody sandwiches.

Sensibeads are addcd and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Scnsibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the cardiac troponin I concentration in the sample.

The CTNI Sample Diluent is a liquid, human serum based product with prescrvatives.

AI/ML Overview

Here's an analysis of the provided text, focusing on acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

Criteria Category	Acceptance Criteria (Implicit)	Reported Device Performance	Comments
Substantial Equivalence to Predicate Device	Demonstrated through method comparison. Parameters like slope, y-intercept, and correlation coefficient should indicate high agreement.	Method Comparison Statistics: - Slope: 1.0325 - Y-intercept: -0.0284 ng/mL - Correlation Coefficient (r): 0.998 - Sample Size (n): 229	The reported performance (r = 0.998) shows a very strong linear relationship and excellent agreement between the new device and the predicate device. The slope being close to 1 and the y-intercept close to 0 also confirm this. While explicit acceptance criteria values (e.g., "slope between 0.95 and 1.05") are not stated, the results are overwhelmingly indicative of meeting an implicit acceptance of strong agreement.
Intended Use	The device performs its intended function: quantitative measurement of cardiac troponin I in human serum and plasma for diagnosis of AMI and risk stratification.	Stated Intended Use is identical to the predicate device.	No specific performance metrics are provided here, but the claim of substantial equivalence implies the new device also serves this intended use effectively.
Sample Type	Accepts human serum and plasma.	The device accepts human serum and plasma, identical to the predicate.	No specific performance metrics here, but adherence to sample type is confirmed.
Assay Range	Must have an appropriate and comparable assay range to the predicate.	New device assay range: 0.017-40 ng/mL. Predicate device assay range: 0.015-40 ng/mL.	The assay ranges are very similar, indicating comparable analytical capability at both the low and high ends.

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

Test Set Sample Size: 229 human serum and plasma samples.
Data Provenance: Not explicitly stated regarding country of origin. The study involves "human serum and plasma samples," implying clinical samples. It is a "split sample method comparison study," which means a single set of samples was tested on both the new device and the predicate device. This is a retrospective approach as it uses existing biological samples to compare device performance.

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

Not applicable / Not provided. For this type of study (method comparison for an in vitro diagnostic device measuring a biomarker), "ground truth" isn't typically established by human experts in the same way it would be for image interpretation. Instead, the predicate device's measurement of cardiac troponin I serves as the reference or comparator. The "ground truth" implicitly relies on the established accuracy and reliability of the predicate device itself, which would have undergone its own validation studies.

4. Adjudication Method for the Test Set

Not applicable / Not provided. Since the study is a direct method comparison between two quantitative assays, there's no "adjudication" in the sense of reconciling divergent expert opinions or labeling. The comparison relies on statistical analysis of quantitative measurements.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is typically used for diagnostic imaging devices where human readers interpret medical images, and the AI's impact on their performance is assessed. This document describes an in vitro diagnostic (IVD) device, specifically a blood test for a biomarker, which does not involve human readers interpreting "cases" in the medical imaging sense.

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

Yes, a standalone performance assessment was effectively done. The "method comparison" study directly assessed the performance of the new device (the algorithm/reagent system) against the predicate device without human interpretation affecting the quantitative output. The results (slope, y-intercept, r-value) directly reflect the standalone analytical performance of the new system.

7. The Type of Ground Truth Used

The "ground truth" for this study is the measurement obtained from the predicate device, the Dimension Vista® CTNI Flex® reagent cartridge. The study assumes that the predicate device provides accurate and reliable measurements of cardiac troponin I.

8. The Sample Size for the Training Set

Not provided. This document describes a submission for a medical device (a reagent cartridge) that measures a biomarker. While such devices have analytical characteristics that are "trained" or optimized during their development, this specific 510(k) summary focuses on demonstrating substantial equivalence to an existing predicate device using a method comparison study. It does not detail the internal development or "training" data used to optimize the assay's performance characteristics. This information is typically proprietary and not part of a 510(k) summary focused on equivalence.

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

Not provided. Similar to point 8, the methodology for establishing "ground truth" for any internal training or development data is not disclosed in this 510(k) summary. For biochemical assays, this would typically involve a combination of:
- Using reference materials with known concentrations.
- Comparing against highly accurate but perhaps less high-throughput reference methods (e.g., mass spectrometry).
- Spiking studies where known analyte concentrations are added to samples.
- Evaluating linearity and recovery across the analytical range.

Summary

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

510(k) Summary of Safety and Effectiveness Dimension® TNI Flex® reagent cartridge and CTNI Sample Diluent

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.

The assigned 510(k) number is:	K081643
--------------------------------	---------	--

1. Submitter's Contact Information and Date of Preparation

Submitter's Contact Information:	Mrs. Yuk-Ting LewisSiemens Healthcare Diagnostics Inc.P.O. Box 6101Newark, DE 19714Tel: 302-631-7626
Date of Preparation:	June 3, 2008

Proprictary Device Name / FDA Classification Name 2.

Dimension® TNI Flex® reagent cartridge	Immunoassay Method, Troponin submit(21 CFR 862.1215)
CTNI Sample Diluent	No FDA classification

3. Identification of the Predicate Device

Dimension Vista® CTNI Flex® reagent cartridge, K063756 Dimension Vista® CTNI Sample Difuent, K053577

4. Device Description

The Dimension® TNI Flex® reagent cartridge is an in vitro diagnostic device that consists of prepackaged reagents in a plastic eight-well cartridge for use on the Dimension® EXL™ with LM system.

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

The CTNI Sample Diluent is a liquid, human serum based product with prescrvatives.

5. Device Intended Use

Summary of the devices technological characteristics 6.

The Dimension® TNI Flex® reagent cartridge has the same technological characteristics as the predicate device. A comparison of features is provided.

Feature	Predicate Device:Dimension Vista® CTNI Flex®reagent cartridge	New Device:Dimension® TNI Flex® reagentcartridge
Intended Use	Both devices are for in vitro diagnostic use for the quantitative measurementof cardiac troponin I in human serum and plasma.
Sample Type	Acceptable sample types are human serum and plasma.
Assay Range	The Dimension Vista® CTNImethod has an assay range of0.015-40 ng/mL.	The Dimension® TNI method has anassay range of 0.017-40 ng/mL.
Technology	Both devices use LOCI® technology.
Sample Size	Both devices use a sample volume of 20 µL.
Reagents andantibody	Both devices use the same liquid reagents and antibody.
Diluent	Both devices use the CTNI Sample Diluent to manually dilute high samples.
Instrument	The Dimension Vista® CTNIFlex® is run on the DimensionVista® analyzer.	The Dimension® TNI Flex® is runon the Dimension® EXLTM systemwith the LOCI module.

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

7. Method Comparison to the predicate

A split sample method comparison study was conducted on the Dimension® TNI Flex® vs. the Dimension® Vista CTNI Flex® reagent cartridge using two hundred-and-twenty nine (229) serum and plasma samples. The data was analyzed using least squares linear regression. The resulting regression statistics are shown below.

Slope	1.0325
y-int	-0.0284 ng/mL
r	0.998
n	229

8. Conclusion

・

Based on a review of the devices technological features and the method comparison study, the Dimension® TNI Flex® reagent cartridge is substantially equivalent to the legally marketed device, the Dimension Vista® CTNI Flex® reagent cartridge.

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

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/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 its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged in a circular pattern around the eagle. The eagle is depicted in black, and the text is also in black. The overall design is simple and recognizable.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Siemens Healthcare Diagnostics, Inc. c/o Yuk-Ting Lewis RA & Compliance Manager P.O. Box 6101, M/S 514 Newark, DE 19714

JUL - 3 2008

Re: K081643 Trade/Device Name: Dimension® TNI Flex® reagent cartridge CTNI Sample Diluent Regulation Number: 21 CFR §862.1215 Regulation Name: Creatine Phosphokinase/Creatine Kinase or Isoenzymes Test System. Regulatory Class: Class II Product Code: MMI Dated: June 11, 2008 Received: June 12, 2008

Dear Ms. Lewis:

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 (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 yours,

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

Yéan 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

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

Indication for Use

510(k) Number (if known): K081643

Dimension® TNI Flex® reagent cartridge Device Name: CTNI Sample Diluent

Indications For Use:

Method

Diluent

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use _ (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Carol C. Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K081643

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.