(85 days)
The DiaSorin TSH-CTK-3 is an immunoradiometric assay for the quantitative determination of thyrotropin (TSH) in human serum. Measurements of TSH levels are used as an aid in the diagnosis of thyroid or pituitary disorders.
The TSH-CTK-3 is an immunoradiometric assay for the quantitative determination of thyrotropin (TSH) in human serum. Two monoclonal antibodies recognizing different binding sites on the antigen (intact hTSH and ß subunit of TSH) are used in excess. The monoclonal antibody to intact hTSH is labeled with Iodine-125 (tracer). The other monoclonal antibody to the ß subunit of TSH is immobilized on the inner surface of the tube (coated tube system). During the incubation both antibodies react with TSH molecules of the sample to form a sandwich-type complex bound to the tube (bound fraction B). Unbound tracer is removed with a wash step. After the washing step the radioactivity of the tubes is measured. The radioactivity measured is directly proportional to the TSH concentration of the respective sample. Using samples of known TSH concentration (standards) a radioactivity-concentration-profile (standard curve) is constructed by which TSH values of unknown samples can be determined by means of their respective radioactivity. TSH concentrations in terms of mU TSH/L are calibrated against WHO 2nd IRP 80/558.
The TSH-CTK-3 device is an immunoradiometric assay (IRMA) intended for the quantitative determination of Thyrotropin (TSH) in human serum. Measurements of TSH levels are used as an aid in the diagnosis of thyroid and pituitary disorders.
Here's an analysis of its acceptance criteria and the study proving its performance:
1. Table of Acceptance Criteria and Reported Device Performance
| Parameter | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Sensitivity (Analytical) | Not explicitly stated | 0.04 mU/L |
| Sensitivity (Functional) | Not explicitly stated | 0.09 mU/L |
| Total Precision (%CV) | Not explicitly stated | 2% - 13% |
| Recovery (mean) | Not explicitly stated | 98.7% +/- 1.4% |
| Linearity | Correlation coefficient (r) close to 1 | y = 0.93x + 0.52, r = 0.998 |
| Linearity of Dilution | Correlation coefficient (r) close to 1 | y = 1.02x + 0.19, r = 0.999 |
| Endogenous Substance Interference | No significant interference | No significant interference observed at Hemoglobin (500mg/dL), Cholesterol (1000mg/dL), Bilirubin (15mg/dL). Interference observed with Triglycerides (330mg/dL) |
| Sample Types | Serum only | Serum. (Note: Serum and Plasma show some differences, so intended use is for Serum only.) |
| Reference Range (Serum Only) | Established range | 0.25 - 3.51 mU/L |
| Method Comparison (vs. Predicate) | High correlation (r) | Correlation coefficient of 0.99 with Ventrex hTSH 125I IRMA kit |
Note: The document provided does not explicitly state numerical acceptance criteria for many parameters, but rather reports the performance results. The implication for parameters like linearity and method comparison is that a high correlation coefficient (close to 1) indicates acceptable performance. For sensitivity and precision, the reported values are presented as the device's performance characteristics.
2. Sample Size Used for the Test Set and Data Provenance
- Analytical Sensitivity: 40 replicates of the zero standard. Data provenance is not specified but appears to be from internal laboratory testing.
- Functional Sensitivity: 14 serum pools, assayed in 1 run per day for 5 days. Data provenance is not specified but appears to be from internal laboratory testing.
- Total Precision: Not specified for the number of samples, but determined according to NCCLS guidelines. Data provenance is not specified but appears to be from internal laboratory testing.
- Linearity/Linearity of Dilution: Not specified for the number of samples, but "samples" were diluted. Data provenance is not specified but appears to be from internal laboratory testing.
- Endogenous Substance Interference: Not specified for the number of samples, but tested with specific concentrations of hemoglobin, cholesterol, bilirubin, and triglycerides. Data provenance is not specified but appears to be from internal laboratory testing.
- Method Comparison: 95 individuals. Data provenance is not specified but implies a clinical sample set. The study type is retrospective, as existing samples from individuals were evaluated in both kits.
- Reference Range: 100 apparently healthy adults from Western Europe. This is prospective for establishing the reference range for the device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an in-vitro diagnostic (IVD) assay for measuring a specific biomarker (TSH). The "ground truth" for such assays is typically established through biochemical methods, reference materials, and comparison to established predicate devices, rather than expert interpretation of images or observations.
- Standards/Calibration: Calibrated against WHO 2nd IRP 80/558. This is a globally recognized reference standard for TSH.
- Method Comparison: Compared against the Ventrex hTSH 125I IRMA kit (predicate device). The predicate device itself has established performance based on previous regulatory approvals.
Therefore, the concept of "experts establishing ground truth" in the manner of radiologists or pathologists for, say, an imaging device, does not directly apply here. The accuracy of the measurements itself, validated against reference standards and predicate devices, constitutes the "ground truth establishment." No specific number or qualifications of "experts" are stated in this context.
4. Adjudication Method for the Test Set
Not applicable in the context of a biochemical assay where quantitative measurements are directly compared to reference standards or predicate device results. There is no subjective interpretation requiring adjudication.
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 relevant for diagnostic devices that involve human interpretation (e.g., imaging devices read by radiologists). This device is an automated biochemical assay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, the performance data presented is for the standalone performance of the TSH-CTK-3 assay. It describes the analytical and functional characteristics of the device itself (e.g., sensitivity, precision, recovery, linearity, interference, method comparison) without human intervention in the measurement process after sample processing.
7. The Type of Ground Truth Used
- Reference Standard: WHO 2nd IRP 80/558 was used for calibrating TSH concentrations.
- Comparison to Predicate Device: The Ventrex hTSH 125I IRMA kit served as the comparative ground truth for method comparison.
- Biochemical Measurement: The inherent biochemical properties and accurate measurement of TSH concentration are the fundamental ground truth for this type of assay.
8. The Sample Size for the Training Set
This document does not specify a separate "training set" in the context of machine learning or AI algorithms. For traditional IVD assays like this IRMA, the development process involves using various samples (standards, controls, patient samples) during optimization and calibration. The "standards" (seven levels, human serum based) used to construct the radioactivity-concentration-profile serve as a form of calibration data, but the term "training set" with its specific implications for AI is not used or applicable here.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" in the AI sense is not applicable. For establishing the calibration curve (analogous to the "learning" phase for an assay), the device uses:
- Known TSH Concentrations (Standards): Seven levels of human serum-based standards with nominal concentrations ranging from 0.02-0.92 mU/L.
- Standardization: These standards are stated to be "Standardized against the World Health Organization (WHO) Reference Program 80/558." This means their TSH concentrations were accurately determined and traceable to an international reference material, establishing their "ground truth" for calibration purposes.
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K041014 72
JUL 1 4 2004
SUBMITTED BY: DiaSorin Inc.
510(k) Summary
David Ikeda
1951 Northwestern Ave. P.O. Box 285 Stillwater, MN 55082-0285 651.351.5592 Voice 651.351.5669 Fax March 31, 2004
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| NAME OF DEVICE: | |
|---|---|
| Trade Name | TSH-CTK-3 |
| Common Name/Description | Immunoradiometric assay (IRMA) for thequantitative determination of Thyrotropin |
| Classification Name: | Thyroid Stimulating Hormone Test System |
| PREDICATE DEVICE: | Ventrex hTSH 125I IRMA |
INTENDED USE: The TSH-CTK-3 is an immunoradiometric assay (IRMA) for the quantitative determination of Thyroid Stimulating Hormone(Thyrotropin) in human serum. Measurements of TSH levels are used as an aid in the diagnosis of thyroid and pituitary disorders.
DEVICE DESCRIPTION: The TSH-CTK-3 is an immunoradiometric assay for the quantitative determination of thyrotropin (TSH) in human serum. Two monoclonal antibodies recognizing different binding sites on the antigen (intact hTSH and ß subunit of TSH) are used in excess. The monoclonal antibody to intact hTSH is labeled with Iodine-125 (tracer). The other monoclonal antibody to the ß subunit of TSH is immobilized on the inner surface of the tube (coated tube system). During the incubation both antibodies react with TSH molecules of the sample to form a sandwich-type complex bound to the tube (bound fraction B). Unbound tracer is removed with a wash step. After the washing step the radioactivity of the tubes is measured. The radioactivity measured is directly proportional to the TSH concentration of the respective sample. Using samples of known TSH concentration (standards) a radioactivity-concentration-profile (standard curve) is constructed by which TSH values of unknown samples can be determined by means of their respective radioactivity. TSH concentrations in terms of mU TSH/L are calibrated against WHO 2nd IRP 80/558.
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| TECHNOLOGICAL COMPARISON TO PREDICATE: | ||
|---|---|---|
| ---------------------------------------- | -- | -- |
| Feature | Ventrex hTSH 125I IRMA (K920856) | TSH-CTK-3 |
|---|---|---|
| Analyte | Thyroid Stimulating Hormone(hTSH) | Thyroid Stimulating Hormone (hTSH) |
| IntendedUse | FOR in vitro DIAGNOSTIC USE.The Ventrex hTSH 125I IRMA kit is to beused for the quantitativedetermination of TSH (thyroid stimulatinghormone) concentrationin serum. | FOR in vitro DIAGNOSTIC USE.The DiaSorin TSH-CTK-3 is an immuno-radiometric assay for the determination ofthyrotropin(TSH) in human serum.Measurements of TSH are used as an aid inthe diagnosis of thyroid and pituitarydisorders. |
| AssayType | IRMA | IRMA |
| Coated | Mouse Monoclonal Anti-hTSH | Mouse Monoclonal Anti-Thyrotropinantibody |
| TubeTracer | 125I Goat Anti-hTSH | 125I Mouse Monoclonal Anti-Thyrotropinantibody |
| Standards | Eight levels, porcine serum based withnominal concentrations ranging from0.125-100mIU/L. Standardizedagainst the World Health Organization(WHO) Reference Program 80/558. | Seven levels, human serum based withnominal concentrations ranging from0.02-0.92mU/L. Standardized againstthe World Health Organization (WHO)Reference Program 80/558. |
| KitControls | None provided with the kit. | Three levels, human serum based. |
PERFORMANCE DATA: A summary of performance data is shown below.
| Parameter | Performance Results |
|---|---|
| Sensitivity (Analytical) | 0.04 mU/L |
| Sensitivity (Functional) | 0.09 mU/L |
| Total Precision(%CV) | 2% - 13% |
| Recovery(mean) | 98.7% +/- 1.4% |
| Linearity | y = 0.93x + 0.52, r = 0.998 |
| Linearity of Dilution | y = 1.02x + 0.19, r = 0.999 |
| Endogenous Substance Interference | No significant interference was observed atthe following concentrations: Hemoglobin(500mg/dL),Cholesterol (1000mg/dL) and Bilirubin (15mg/dL).Interference was observed with Triglycerides(330mg/dL) |
| Sample Types | Serum. |
| Reference Range(Serum Only) | 0.25 - 3.51 mU/L |
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Analytical Sensitivity was determined from 40 replicates of the zero standard (mean =71cpm). Functional Sensitivity was determined from 14 serum pools assayed in 1 run per day for 5 days (mean 0.09mU/L). Total Precision was determined to be 2% to 13% across the range of the assay according to NCCLS guidelines. Samples diluted linearly with a correlation coefficient of 0.999. Serum and Plasma do show some differences, so the intended use will be for Serum only. Samples frozen for 24 hrs gave similar results for hTSH, as samples stored at 4°C for 24hrs. The method comparison was conducted according to the guidelines in NCCLS reference document EP9-A2. Samples from 95 individuals spanning the assay range were evaluated in both kits. The TSH-CTK-3 assay correlated well with the Ventrex hTSH 125 IRMA kit, with a correlation coefficient of 0.99. The serum sample reference interval was established using 100 apparently healthy adults from Western Europe (0.25 – 3.51 mU/L, 95% confidence intervals).
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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 circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.
Public Health Service
Food and Drug Administratio 2098 Gaither Road Rockville MD 20850
JUL 1 4 2004
Mr. David M. Ikeda DiaSorin Inc. Manager, Regulatory Affairs & Quality Systems 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285
K041014 Re:
Trade/Device Name: TSH-CTK-3 Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid stimulating hormone test system Regulatory Class: Class II Product Code: JLW, JIT, JJX Dated: June 24, 2004 Received: June 29, 2004
Dear Mr. Ikeda:
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 Cosnietic 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 (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,
Seain M. Cooper, US, Dvim.
Jean M. Cooper, MS, 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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Indications for Use
510(k) Number (if known): _ K041014
Device Name: TSH-CTK-3
Indications For Use:
The DiaSorin TSH-CTK-3 is an immunoradiometric assay for the quantitative determination of thyrotropin (TSH) in human serum. Measurements of TSH levels are used as an aid in the diagnosis of thyroid or pituitary disorders.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 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
Division Sign-Off
Office of In Vitro Diagnostic
Device Evaluation and Safety
5100 K04/014
§ 862.1690 Thyroid stimulating hormone test system.
(a)
Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.(b)
Classification. Class II.