(63 days)
Not Found
No
The device description details a standard immunoassay technology (LOCI) and does not mention any AI or ML components in its operation or data analysis. The performance studies focus on traditional analytical and clinical metrics.
No.
This device is an in vitro diagnostic (IVD) assay designed to measure cardiac troponin I in human plasma to aid in the diagnosis of acute myocardial infarction (AMI). It is used for diagnostic purposes, not for treating or preventing disease.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the assay "can be used to aid in the diagnosis of acute myocardial infarction (AMI)," which is a diagnostic purpose.
No
The device is an in vitro diagnostic assay that measures cardiac troponin I in human plasma using a specific integrated chemistry system (Dimension EXL with LOCI module). This involves physical reagents and a hardware system for analysis, not just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states, "The Dimension EXL High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use..." It also describes its use in the quantitative measurement of cardiac troponin I in human plasma to aid in the diagnosis of acute myocardial infarction (AMI), which is a diagnostic purpose performed outside of the body.
- Device Description: The description details a laboratory assay that analyzes human plasma samples using chemical and immunological reactions to measure a specific analyte (cardiac troponin I). This is characteristic of an in vitro diagnostic device.
- Performance Studies: The document describes various analytical and clinical performance studies conducted on human body fluids (plasma) to validate the assay's performance for diagnostic purposes.
- Key Metrics: The evaluation of clinical sensitivity, specificity, PPV, and NPV are standard metrics used to assess the performance of diagnostic tests.
All these elements clearly indicate that the Dimension EXL High-Sensitivity Troponin I (TNIH) assay is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Dimension EXL High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human plasma using the Dimension EXL integrated chemistry system with LOCI module. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
Product codes
MMI
Device Description
The Dimension EXL TNIH assay is a homogeneous, sandwich chemiluminescent immunoassay based on LOCl® technology. The LOCI reagents include two synthetic bead reagents and two biotinylated anti-cardiac troponin I monoclonal antibody fragments. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with a third anticardiac troponin I monoclonal antibody and contains chemilyminescent dve. Sample is incubated with Chemibeads and biotinylated antibodies to form bead-cardiac troponin Ibiotinylated antibody sandwiches. Sensibeads are added and bind to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads 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. Lithium heparin plasma specimens may be used. The reagent is stored unopened at 2-8 °C, is stable sealed on system for 30 days and opened on the system for 7 days. Calibration is performed every 21 days for a reagent lot.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
The 99th percentile values were determined using the non-parametric statistical method described in CLSI Guidance EP28-A3c. Sample type, gender, and age had no statistically significant effect on the 99th percentile.
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
A prospective study was performed to assess diagnostic accuracy for approximately 2500 subjects in lithium heparin plasma sample types to evaluate clinical performance. Specimens were collected at 29 emergency departments across the United States, from subjects presenting with symptoms consistent with acute coronary syndrome (ACS). All subject diagnoses were adjudicated by panels of certified cardiologists and emergency physicians according to the Third Universal Definition Of Myocardial Infarction - consensus guideline endorsed by the European Society of Cardiology (ESC), the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), and the World Heart Federation (WHF). The observed AMI prevalence in this study was 13.0 %.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Assay performance results for the Dimension EXL High-Sensitivity Troponin I (TNIH) assay was determined by processing the appropriate body fluids. Summary statistics for each are provided. The following data represent typical assay performance. All data were collected on the Dimension EXL with LM System.
LoB was 1.0 pg/mL
LoD was 1.0 - 1.8 pg/mL
The LoQ for TNIH of 4.0 pq/mL is consistent with the data.
The 10% CV limit for Dimension EXL TNIH of 12.0 pg/mL is consistent with the data.
Precision Study: All precision goals were met.
Plasma 1: Mean 48.0 pg/mL, SD 1.11 pg/mL, %CV 2.3 (Repeatability); SD 2.87 pg/mL, %CV 6.0 (Within-Lab)
Plasma 2: Mean 71.8 pg/mL, SD 1.45 pg/mL, %CV 2.0 (Repeatability); SD 2.09 pg/mL, %CV 2.9 (Within-Lab)
Plasma 3: Mean 155.7 pg/mL, SD 2.75 pg/mL, %CV 1.8 (Repeatability); SD 4.62 pg/mL, %CV 3.0 (Within-Lab)
QC: Mean 7411.7 pg/mL, SD 145.59 pg/mL, %CV 2.0 (Repeatability); SD 246.56 pg/mL, %CV 3.3 (Within-Lab)
Linearity from 4.0 - 25,000.0 pg/mL was confirmed.
Interferences: No interference was detected at the following analyte concentrations for Hemoglobin, Bilirubin (conjugated & unconjugated), and Lipemia. Various other potential interferents showed no interference at low/therapeutic and high/toxic concentrations.
No hook effect was found at 1,000,000 pg/mL troponin on the Dimension EXL TNIH assay.
Calibration interval was measured to be 21 days due to sufficient stability.
Open well stability of the reagents opened onboard the instrument was 7 days per well set.
Sample Stability: Separated samples are stable for 8 hours at room temperature and for 24 hours when stored at 2-8 °C. Samples can be frozen at or below -20 °C for up to 40 days in a nonfrost free freezer and at or below -70 ℃ for up to 1 year.
Expected Values: The overall observed 99th percentile of 60.4 pg/mL [ng/L] for combined gender and lithium heparin plasma. Female 99th percentile was 51.4 pg/mL and Male 99th percentile was 76.2 pg/mL.
Clinical Performance: The clinical concordance study evaluated clinical sensitivity, clinical specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Dimension EXL TNIH assay in terms of its correlation to the diagnosis of AMI.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Lithium Heparin Plasma (Pooled Gender, 99th percentile of 60.4 pg/mL)
- **0-
§ 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.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
May 17, 2019
Siemens Healthcare Diagnostics, Inc. Laura Duggan Sr. Mgr. Regulatory Affairs 500 GBC Drive Newark, DE 19714
Re: K190675
Trade/Device Name: Dimension EXL High-Sensitivity Troponin I (TNIH) Assay Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: Class II Product Code: MMI Dated: March 18, 2019 Received: March 19, 2019
Dear Laura Duggan:
We have reviewed vour 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. 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 located at https://www.accessdata.fda.gov/scripts/cdrh/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.
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
1
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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
for Kellie B. Kelm. Ph.D. Acting Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure:
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K190675
Device Name
Dimension EXL High-Sensitivity Troponin I (TNIH) assay
Indications for Use (Describe)
The Dimension EXL High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human plasma using the Dimension EXL integrated chemistry system with LOCI module. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
X Prescription Use (Part 21 CFR 801 Subpart D)
] Over-The-Counter Use (21 CFR 801 Subpart C)
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SECTION 7: 510(K) SUMMARY
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
ASSIGNED 510(K) NUMBER
The assigned 510(k) number is k190675_________________________________________________________________________________________________________________________________
APPLICANT AND DATE
Laura J. Duggan, Ph. D., RAC Siemens Healthcare Diagnostics Inc. 500 GBC Drive, M/S 514 Newark, DE 19714-6101 Email: laura.j.duggan@siemens-healthineers.com Phone: 302-631-7654 Fax: 302-631-0493
March 14. 2019
MANUFACTURER
Siemens Healthcare Diagnostics Inc. 500 GBC Drive Newark, DE 19714-6101
Registration Number: 2517506
REGULATORY INFORMATION
Regulatory Submission for the Dimension EXL High-Sensitivity Troponin I (TNIH) Assay
| Device: | Immunoassay method, troponin subunit |
|---|---|
| Regulation Description: | Creatine phosphokinase/creatine kinase or isoenzymes test system |
| Proprietary Name: | Dimension EXL High-Sensitivity Troponin I (TNIH) Assay |
| Regulation Number: | 21CFR862.1215 |
| Classification: | Class II |
| Product Code: | MMI |
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| Panel: | Clinical Chemistry |
|---|---|
| Predicate Device: | Elecsys Troponin T Gen 5 STAT |
| (K162895) |
DEVICE DESCRIPTION
DIMENSION EXL HIGH-SENSITIVITY TROPONIN I (TNIH) ASSAY
The Dimension EXL TNIH assay is a homogeneous, sandwich chemiluminescent immunoassay based on LOCl® technology. The LOCI reagents include two synthetic bead reagents and two biotinylated anti-cardiac troponin I monoclonal antibody fragments. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with a third anticardiac troponin I monoclonal antibody and contains chemilyminescent dve. Sample is incubated with Chemibeads and biotinylated antibodies to form bead-cardiac troponin Ibiotinylated antibody sandwiches. Sensibeads are added and bind to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads 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
Lithium heparin plasma specimens may be used. The reagent is stored unopened at 2 -8 °C, is stable sealed on system for 30 days and opened on the system for 7 days. Calibration is performed every 21 days for a reagent lot.
INTENDED USE/INDICATIONS FOR USE
DIMENSION EXL HIGH-SENSITIVITY TROPONIN I (TNIH) ASSAY
The Dimension EXL High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human plasma using the Dimension EXL integrated chemistry system with LOCI module. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
SUBSTANTIAL EQUIVALENCE COMPARISON
Below is a substantial equivalence comparison for the Dimension EXL High-Sensitivity Troponin I (TNIH) Assay vs. the Elecsys Troponin T Gen 5 STAT (K162895) device.
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| Feature | Predicate Device:
Elecsys Troponin T Gen 5
STAT (K162895) | New Device:
DIMENSION EXL HIGH-
SENSITIVITY TROPONIN I
(TNIH) ASSAY | |
|-----------------------------------|--------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| Intended Use : | Immunoassay for the in vitro
quantitative determination of
cardiac troponin T (cTnT) in
lithium heparin plasma. | The Dimension EXL High-
Sensitivity Troponin I (TNIH)
assay is for in vitro diagnostic
use in the quantitative
measurement of cardiac
troponin I in human plasma
using the
Dimension EXL integrated
chemistry system with LOCI
module. | |
| Indications for Use: | The immunoassay is
intended to aid in the
diagnosis of myocardial
infarction. | The assay can be used to aid
in the diagnosis of acute
myocardial infarction (AMI). | |
| Device Technology: | Electrochemiluminescence
immunoassay | Homogeneous immunoassay | |
| Sample Type: | Lithium Heparin Plasma | Lithium Heparin plasma | |
| Expected Values: | 99th percentile
were determined to be:
• 19 ng/L for both
• 14 ng/L for females
• 22 ng/L for males | 99th percentile determined for
for plasma
60.4 pg/mL overall
female 51.4 pg/mL plasma
male 76.2 pg/mL plasma | |
| Calibration
Frequency: | after 12 weeks when using
the same reagent lot | 21 days for any one lot | |
| Analytical Measuring
Interval: | 6-10,000 ng/L | 4.0 - 25,000.0 pg/mL [ng/L] | |
| Interferences: | No interference in plasma at:
Hemoglobin - 100 mg/dL
Bilirubin 25 mg/dL
Lipemia (Intralipid®) – 1500
mg/dL | No interferences in plasma at
approximately 40 pg/mL and
approximately 1350 pg/mL of
cardiac troponin I from:
Hemoglobin - 400 mg/dL | |
| | | Bilirubin (Unconjugated) – 40
mg/dL
Bilirubin (Conjugated) – 30
md/dL
Lipemia (Intralipid®) – 3000
mg/dL | |
| Calibrators: | Elecsys Troponin T Gen 5
STAT calibrators (CalSet
Troponin T Gen 5 STAT) | LOCI TNIH Calibrator, Cat.
No. RC627 | |
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SUMMARY OF PERFORMANCE TESTING
Assay performance results for the Dimension EXL High-Sensitivity Troponin I (TNIH) assay was determined by processing the appropriate body fluids. Summary statistics for each are provided. The following data represent typical assay performance. All data were collected on the Dimension EXL with LM System.
DETECTION LIMIT
The Limit of Blank (LoB) and Limit of Detection (LoD) were evaluated in accordance with CLSI EP17-A2 Protocols for Determination of Limits of Detection and Limits of Quantitation: Approved Guideline.
Assessment of LoB was the 95th percentile of all values (sorted from lowest to highest), using non-parametric approach. LoB Rank Position = 0.5 +0.95*B, where B=total reps=60; Rank = 57.5
The nonparametric approach described in EP17-A2 was followed to determine the Limit of Detection. LoD was tested separately for lithium heparin specimens.
| Dimension EXL High-Sensitivity Troponin I (TNIH) - Limit of Detection Results | ||
|---|---|---|
| Limit | Protocol | Result |
| LoB | 5 samples with no analyte (calibrator Level A, | |
| BSA based with HEPES buffer 5 individual vials) | ||
| were tested (N=4) for 3 days, one run per day, 3 | ||
| reagent lots | 1.0 pg/mL | |
| LoD | At least 5 low analyte samples were tested (N=4) | |
| for 3 days for native lithium heparin plasma, one | ||
| run per day, 3 reagent lots | 1.0 - 1.8 | |
| pg/mL |
Results are consistent with the claim of 2.7 pg/mL for LoD and 1.1 pg/mL for LoB.
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The Limit of Quantitation (LoQ) for plasma was determined as the analyte level with a within-lab CV of less than or equal to 20.0%. Testing was completed two times a day (n=2) for at least 20 days for a total of 80 replicates with at least 6 native lithium heparin plasma pools on one instrument.
LoQ Lot Summary
| Reagent Lot | Lot-1 | Lot-2 | Lot-3 |
|---|---|---|---|
| Lithium Heparin Plasma 20% CV (pg/mL) | 1.1 | 2.1 | 2.3 |
The LoQ for TNIH of 4.0 pq/mL is consistent with the data.
10% CV LIMIT
For lithium heparin plasma the analyte level with a within-lab CV of less than or equal to 10.0% was determined using CLSI EP5-A3, Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline - Third Edition. Testing was completed two times a day (n=2) for at least 20 days for a total of 80 replicates with at least 6 native lithium heparin plasma pools on one instrument.
10% CV Lot Summary
| Reagent Lot | Lot-1 | Lot-2 | Lot-3 |
|---|---|---|---|
| Lithium Heparin Plasma 10% CV (pg/mL) | 3.2 | 5.3 | 5.8 |
The 10% CV limit for Dimension EXL TNIH of 12.0 pg/mL is consistent with the data.
PRECISION STUDIES
Precision testing was performed in accordance with CLSI EP05-A3 Evaluation of Precision Performance of Quantitative Measurement Methods: Approved Guideline -Third Edition. Precision was tested n = 2 replicates, two times a day for at least 20 days for a total of 80 replicates with controls and plasma pools on one instrument. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of EP05-A3. The data are summarized in the following table. All precision goals were met.
| Repeatability | Within-Lab | ||||
|---|---|---|---|---|---|
| Material | Mean pg/mL [ng/L] | SDa pg/mL [ng/L] | %CVb | SD pg/mL [ng/L] | %CV |
| Plasma 1 | 48.0 | 1.11 | 2.3 | 2.87 | 6.0 |
| Plasma 2 | 71.8 | 1.45 | 2.0 | 2.09 | 2.9 |
| Plasma 3 | 155.7 | 2.75 | 1.8 | 4.62 | 3.0 |
| QC | 7411.7 | 145.59 | 2.0 | 246.56 | 3.3 |
ªSD = standard deviation
b CV = coefficient of variation
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Linearity was evaluated with 16 lithium heparin plasma samples which spanned the assay measuring interval. Each was prepared by mixing high and low concentration samples across the measurement interval as described in CLSI Evaluation of the Linearity of Quantitative Measurement Procedure (EP06-A). The high samples and the low samples for lithium heparin plasma were native. At least five replicates were measured for each sample. The mean of these replicates was used for the calculations.
The assay was considered linear across the measuring interval if the p values of nonlinear terms in the quadratic and cubic fit equations are nonsignificant (p ≤ 0.05). If the p-value is > 0.05, then the allowable bias is ≤ 10% or 4 pg/mL, whichever is greater.
The testing confirmed linearity from 4.0 - 25,000.0 pg/mL.
INTERFERENCES
CLSI EP7-A2 was followed for the interference testing. The interference study was conducted using a "paired difference scenario" approach where these compounds were spiked into fresh sample pools containing either low or high levels of troponin in lithium heparin troponin I pools. All exogeneous compounds were spiked into the troponin control pools at two levels. Endogeneous compounds were only tested at elevated levels as they are natively found in specimen samples.
Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent) expressed in percent. Bias exceeding 10% is considered interference. Dilution studies were conducted to determine the level at which the spiked substance no longer displayed significant interference. Dilution studies were conducted at two analyte concentrations, if both sample pools show significant interference.
| Substance Tested | Substance concentration | Bias (%) |
|---|---|---|
| Hemoglobin hemolysate (monomer) | 400 mg/dL [0.25 mmol/L] |