(414 days)
VIDAS® Troponin I Ultra is an automated quantitative test for use on the VIDAS instruments for the determination of human cardiac troponin I in human serum or plasma (lithium heparin) using the ELFA (Enzymc-Linked Fluorescent Assay) technique. VIDAS Troponin I Ultra is intended to be used as an aid in the diagnosis of myocardial infarction.
The VIDAS Troponin I Ultra (TNIU) Assay is an enzyme-linked fluorescent immunoassay (ELFA) performed in an automated VIDAS® instrument. All assay steps and assay temperature are controlled by the instrument. A pipette tip-like disposable device, the Solid Phase Receptacle (SPR), serves as the solid phase as well as a pipettor for the assay. Reagents for the assay are in the sealed TNIU Reagent Strips. The sample is transferred into the wells containing anti-cardiac troponin i antibodies labeled with alkaline phosphatase (conjugate). The sample/conjugate mixture is cycled in and out of the SPR for a specified length of time. Troponin I present in the specimen will bind to the anticardiac troponin i immunoglobulin coating the interior of the SPR. Unbound sample components are washed away. A fluorescent substrate, 4-methylumbellifery| phosphate, is introduced into the SPR. Enzyme remaining on the SPR wall will catalyze the conversion of the substrate to the fluorescent product 4-methylumbelliferone. The optical scanner in the instrument measures the intensity of fluorescence. When the VIDAS TNIU assay is completed, the results are analyzed automatically by the computer, a test value is generated, and a report is printed for each sample.
Here's a breakdown of the acceptance criteria and study information for the VIDAS® Troponin I Ultra (TNIU) Assay, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a separate section with specific numerical targets. Instead, it presents performance data for both the VIDAS® TNIU and the predicate device (Dimension RxL® CTNI) for comparison, implying that similar or improved performance relative to the predicate device is the goal for most parameters, and certain established clinical cut-offs are considered.
Given this, I've constructed a table focusing on the performance characteristics that were measured and compared, as these implicitly serve as the basis for demonstrating substantial equivalence.
| Acceptance Criteria (Implied / Comparison Target) | Reported Device Performance (VIDAS® TNIU) | Predicate Device Performance (Dimension RxL® CTNI) |
|---|---|---|
| Expected Values (Healthy Patients) | 99% of 747 patients with no cardiac symptoms had values of <0.01 µg/l | 97.5% of 101 apparently healthy patients had values of 0.00 -0.05 µg/L |
| Cut-off | 0.11 µg/l | 0.6-1.5 ng/mL (Note: unit difference) |
| Specificity (Cardiac Troponin T) (at 1000 µg/L) | 0.2% | 0.34% |
| Specificity (Cardiac Troponin C) (at 1000 µg/L) | <0.001 | 0.00% |
| Specificity (Skeletal Troponin I) (at 1000 µg/L) | <0.001 | 0.04% |
| Analytical Detection Limit | < 0.01 µg/l | 0.04 µg/L |
| Dilution - Recovery Test | 80-120% | 98.6-106.4% |
| Interference (Bilirubin) | No significant interference (up to 510 µM) | No significant interference (up to 20 mg/dL) |
| Interference (Hemoglobin) | No significant interference (up to 332 µM) | No significant interference (up to 1000 mg/dL) |
| Interference (Lipemia/Triglycerides) | No significant interference (up to 30 mg/ml) | No significant interference (up to 3000 mg/dL) |
| Hook Effect (up to stated concentration) | No hook effect found up to 1000 µg/L | No hook effect found up to 1800 ng/mL |
| Clinical Method Comparison (Correlation Coefficient) | 0.97 | (N/A - This is a comparison between devices) |
| Clinical Method Comparison (Slope) | 0.42 (Confidence Interval: 0.38-0.44) | (N/A - This is a comparison between devices) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Method Comparison: 534 samples
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). It is described as a "sample comparison study," implying patient samples were collected and tested.
- Sample Size for Expected Values (Healthy Patients):
- VIDAS® TNIU: 747 patients with no cardiac symptoms
- Predicate Device: 101 apparently healthy patients
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Not Applicable (N/A) / Not explicitly stated. This device is an immunoassay for a biomarker (Troponin I). The "ground truth" for analytical performance studies would typically be established by reference measurements (e.g., gold standard analytical methods, spiked samples) or by clinical diagnosis for the "expected values" data, not by expert interpretation of images or symptoms in the same way as, for example, an imaging AI device.
- For the "expected values in healthy patients," the ground truth is simply the clinical status of the patient (e.g., "no cardiac symptoms" or "apparently healthy"). The document doesn't mention expert review of these patient status determinations beyond general clinical criteria.
4. Adjudication Method for the Test Set
- Not Applicable (N/A) / Not mentioned. Adjudication methods like 2+1 or 3+1 are typically used for studies where multiple human readers interpret data (e.g., medical images) and their interpretations need to be reconciled to establish a consensus ground truth. For an immunoassay, the measurement itself is the primary focus, and while clinical diagnosis (the outcome) might involve expert consensus, the assay performance itself is not adjudicated in this manner.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No. An MRMC study is not relevant for this type of in vitro diagnostic device (immunoassay). MRMC studies compare the diagnostic performance of different readers (humans, AI, or human+AI) on a set of cases. This submission is for an automated immunoassay for measuring a biomarker.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Yes, by nature of the device. The VIDAS® TNIU Assay is a standalone automated quantitative test. The results are generated automatically by the instrument, and then a report is printed. There is no explicit "human-in-the-loop" component in the generation of the quantitative result itself, though a clinician would interpret the result in the context of a patient's overall clinical picture. The performance data presented (e.g., correlation, detection limits) directly reflects the standalone performance of the assay.
7. The Type of Ground Truth Used
- Analytical Measurement Comparisons and Clinical Status:
- For Analytical Detection Limit, Dilution-Recovery, Interference, Hook Effect, Specificity: Ground truth is established by the known concentrations of analytes, spiked samples, or absence/presence of interfering substances under laboratory conditions.
- For Expected Values (Healthy Patients): Clinical documentation of the patient's health status (e.g., "no cardiac symptoms" or "apparently healthy") serves as the ground truth for that specific study component.
- For the Clinical Testing (Method Comparison): The "ground truth" is one device's measurement (Dimension RxL® CTNI Assay, the predicate) against which the new device (VIDAS® TNIU Assay) is compared to demonstrate correlation and substantial equivalence.
8. The Sample Size for the Training Set
- Not explicitly stated in relation to algorithm training. This device is an immunoassay, not an AI/machine learning algorithm that requires a "training set" in the conventional sense of computational models. The assay is based on chemical and biological reactions, not statistical pattern recognition trained on a large dataset.
- However, the development of such assays involves extensive research and development with numerous samples to optimize reagents, protocols, and establish performance characteristics, which could be conceptually considered akin to "training" in a broader sense, but not with a distinct "training set" as understood in AI.
9. How the Ground Truth for the Training Set Was Established
- Not applicable (N/A). As explained above, this is an immunoassay, not an AI/machine learning device that uses a "training set" with ground truth in the typical computational sense. The "ground truth" for optimizing the assay would involve using reference materials, known concentrations, and clinical samples whose true values (or clinical diagnoses) were independently established.
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DEC 1 4 2007
510(k) SUMMARY
VIDAS® Troponin | Ultra (TNIU) Assay
A. Submitter Information
| Submitter's Name:Address: | bioMérieux, Inc.595 Anglum RoadHazelwood, MO 63042 |
|---|---|
| Contact Person: | Nikita S. Mapp |
| Phone Number: | 314-731-7474 |
| Fax Number: | 314-731-8689 |
| Date of Preparation: | August 11, 2006 |
B. Device Name
| Trade Name: | VIDAS® Troponin I Ultra (TNIU) Assay |
|---|---|
| Common Name: | Troponin I Enzyme Immunoassay |
| Classification Name: | 21 CFR 862.1215, Product Code MMIImmunoassay method, Troponin Subunit |
C. Predicate Device Name
| Trade Name: | Dimension RxL® Cardiac Troponin I (CTNI) Assay |
|---|---|
| ------------- | ------------------------------------------------ |
D. Device Description
The VIDAS Troponin I Ultra (TNIU) Assay is an enzyme-linked fluorescent immunoassay (ELFA) performed in an automated VIDAS® instrument. All assay steps and assay temperature are controlled by the instrument. A pipette tip-like disposable device, the Solid Phase Receptacle (SPR), serves as the solid phase as well as a pipettor for the assay. Reagents for the assay are in the sealed TNIU Reagent Strips.
The sample is transferred into the wells containing anti-cardiac troponin i antibodies labeled with alkaline phosphatase (conjugate). The sample/conjugate mixture is cycled in and out of the SPR for a specified length of time. Troponin I present in the specimen will bind to the anticardiac troponin i immunoglobulin coating the interior of the SPR. Unbound sample components are washed away.
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A fluorescent substrate, 4-methylumbellifery| phosphate, is introduced into the SPR. Enzyme remaining on the SPR wall will catalyze the conversion of the substrate to the fluorescent product 4-methylumbelliferone. The optical scanner in the instrument measures the intensity of fluorescence. When the VIDAS TNIU assay is completed, the results are analyzed automatically by the computer, a test value is generated, and a report is printed for each sample.
E. Intended Use
VIDAS Troponin I Ultra (TNIU) Assay is an automated quantitative test for use on the VIDAS instruments for the determination of human cardiac troponin I in serum or plasma (lithium heparinate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique.
| Similarities | ||
|---|---|---|
| Item | VIDAS® TNIU | Dimension RxL® CTNI |
| Assay Principle | One-step automated immunoassay based onsandwich principle | Same |
| Intended Use | Quantitative determination of human cardiactroponin I in human serum or plasma (lithiumheparinate) | Same |
| Indications for Use | An aid in the diagnosis of mycocardial infarction | Same |
| Sample Type | Human serum or plasma (lithium heparin) | Same |
| Antibody | Capture: mouse monoclonal antibodyConjugate: mouse monoclonal antibodylabeled with alkaline phosphatase | Same |
F. Technological Characteristics Summary
| Differences | ||
|---|---|---|
| Item | VIDAS® TNIU | Dimension RxL® CTNI |
| Solid Phase | Solid Phase Receptacle (SPR) | Chrome |
| Final Detection oftroponin-I antigen | Fluorescence (ELFA) of 4-methyl-umbelliferyl measured at 450 nm | Colorimetric rate measurement at 510nm |
| Measurement range | 0.01 to 30 µg/L | 0.04 to 40 µg/L |
| Analytical Detection Limit | 0.01 µg/L | 0.04 µg/L |
| Hook effect | No hook effect found up toconcentrations of 1000 µg/L | No hook effect found up toconcentrations of 1800 µg/L |
| Sample Volume | 200 µl | 50 µl |
| Assay Time | ~20 minutes | ~17 minutes |
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G. Performance Data
Nonclinical Testing
| Dimension® RxL CTNI | VIDAS® TNIU | |
|---|---|---|
| Expected Values | 97.5% of 101 apparentlyhealthy patients had valuesof 0.00 -0.05 µg/L | 99% of 747 patients with nocardiac symptoms hadvalues of <0.01 µg/l |
| Cut-off | 0.6-1.5 ng/mL | 0.11 µg/l |
| SpecificityCardiac Troponin T | 1000 µg/L: 0.34% | 1000 µg/L: 0.2% |
| Cardiac Troponin C | 1000 µg/L: 0.00% | 1000 µg/L: <0.001 |
| Skeletal Troponin I | 1000 µg/L: 0.04% | 1000 µg/L: <0.001 |
| Analytical Detection Limit | 0.04 µg/L | < 0.01 µg/l |
| Dilution - Recovery Test | 98.6-106.4% | 80-120% |
| Interference | No significant interference | No significant interference |
| Bilirubin | 20 mg/dL | 510 µM |
| Hemoglobin | 1000 mg/dL | 332 µM |
| Lipemia (triglycerides) | 3000 mg/dL | 30 mg/ml |
| Hook Effect | 1800 ng/mL | 1000 µg/l |
Clinical Testing
Five-hundred and thirty-four samples were tested with both the VIDAS® TNIU Assay (Y) and the Dimension RxL ® CTNI Assay (X). Data from the sample comparison study was evaluated with a Passing-Bablok method and correlation coefficient and produced the following results:
Y = 0.42 X
Confidence interval for the slope: 0.38-0.44 Correlation coefficient = 0.97
H. Conclusion
The VIDAS Troponin I Ultra (TNIU) Assay is substantially equivalent to the Dimension RxL® Cardiac Troponin I (CTNI) Assay.
The 510(k) summary includes only information that is also covered in the body of the 510(k). The summary does not contain any puffery or unsubstantiated labeling claims. The summary does not contain any raw data, i.e., contains only summary data. The summary does not contain any trade secret or confidential commercial information. The summary does not contain any patient identification information.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
DEC 1 4 2007
bioMérieux, Inc. c/o Ms. Nikita S. Mapp Senior Regulatory Affairs Specialist 595 Anglum Road Hazelwood, MO 63042
Re: K063243 Trade/Device Name: Vidas Troponin I Ultra (TNIU) Assay, Model 30 448 21 CFR 862.1215 Regulation Number: Regulation Name: Creatine Phosphokinase/Creatine Kinase or Isoenzymes Test System. Regulatory Class: Class II Product Code: MMI Dated: September 14, 2007 Received: September 17, 2007
Dear Ms. Mapp:
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).
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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. Coopes, 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
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Indication for Use
510(k) Number (if known): K063243
Device Name: VIDAS Troponin I Ultra (TNIU)
Indication For Use: VIDAS® Troponin I Ultra is an automated quantitative test for use on the VIDAS instruments for the determination of human cardiac troponin I in human serum or plasma (lithium heparin) using the ELFA (Enzymc-Linked Fluorescent Assay) technique. VIDAS Troponin I Ultra is intended to be used as an aid in the diagnosis of myocardial infarction.
Prescription Use (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) K063243
§ 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.