(56 days)
This in vitro diagnostic method is intended to quantitatively measure thyroid stimulating hormone in human serum or plasma on the Bayer Immuno 1 System. Measurements of TSH, with a 3td Generation sensitivity of <20% total CV at 0.01 uIUmL to 0.02 µIU/mL (as defined by the American Thyroid Association), are used as an aid in the diagnosis of thyroid or pituitary disorders.
This diagnostic method is not intended for use on any other system.
Not Found
Here's an analysis of the provided text regarding the acceptance criteria and the study proving the device meets them:
Device: 3rd Generation TSH Method for the Bayer Immuno 1™ System
Intended Use: To quantitatively measure thyroid stimulating hormone (TSH) in human serum or plasma with 3rd generation sensitivity on the Bayer Immuno 1 System, for use in the diagnosis of thyroid or pituitary disorders.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the performance benchmarks set against legally marketed predicate devices (Bayer Immuno 1 TSH Assay, (Chiron) Ciba-Corning ACS™ TSH-3 Assay, and (Roche) Boehringer-Mannheim Elecsys® TSH Assay). The specific acceptance criterion for sensitivity is explicitly stated in the "Indications For Use" as <20% total CV at 0.01 uIU/mL to 0.02 µIU/mL (as defined by the American Thyroid Association).
| Acceptance Criteria Category | Specific Acceptance Criterion | Reported Device Performance (Bayer Immuno 1 3GEN TSH) | Comparison to Predicate Devices (Examples given in text) |
|---|---|---|---|
| Sensitivity | <20% total CV at 0.01-0.02 µIU/mL | At 0.019 µIU/mL: %CV (total) = 5.1% | Meets criteria, and is competitive with/better than some predicate lowest concentration total CVs (e.g., ACS:180 Total CV for 0.1 µIU/mL is 13.0%, Elecsys Total CV for 0.026 µIU/mL is 15.8%) |
| Expected Values (Normal Range) | Comparable to predicate devices. | 0.31 - 4.7 µIU/mL | Within range of common predicate devices (e.g., ACS:180 TSH: 0.47 - 6.9 µIU/mL; Elecsys TSH: 0.25 - 4.2 µIU/mL) |
| Precision (Within-Run) | Low %CV across different TSH concentrations, comparable to predicate devices. | See table in prompt. Example: 0.019 µIU/mL: 4.1% CV; 4.68 µIU/mL: 2.8% CV. | Appears competitive. For instance, at 4.68 µIU/mL, 2.8% CV is better than ACS:180 TSH-3 at 9.0 µIU/mL (1.7% CV) and ACS:180 (within-run) 4.81 µIU/mL (3.3% CV). |
| Precision (Total) | Low %CV across different TSH concentrations, comparable to predicate devices. | See table in prompt. Example: 0.019 µIU/mL: 5.1% CV; 4.68 µIU/mL: 3.1% CV. | Appears competitive and meets the specific sensitivity criterion. |
| Correlation/Regression | High correlation (r value close to 1) and small Sy.x with predicate devices. | Correlation with TSH (2nd Gen): r = 0.998, Sy.x = 1.655.Correlation with ACS:180: r = 0.996, Sy.x = 0.676.Correlation with Elecsys: r = 0.997, Sy.x = 1.049. | All correlations are very high (close to 1), indicating strong agreement with established methods. The Sy.x values are low, suggesting good quantitative agreement. |
| Specificity (Cross-reactivity) | Low or no significant cross-reactivity with structurally similar compounds. | hCG: < 0.001%LH: < 0.001%FSH: < 0.001% | Demonstrates excellent specificity, as these common interfering hormones show negligible cross-reactivity. |
Study Details:
The document describes a series of performance evaluations rather than a single, formal "study" in the clinical trial sense. The data presented covers analytical performance characteristics.
2. Sample Size Used for the Test Set and Data Provenance
- Precision Tests (within-run and total): n = 20 over 10 days for each concentration level tested. This refers to 20 replicates measured over 10 days. The provenance (country of origin, retrospective/prospective) is not specified in the provided text.
- Correlation/Regression Studies:
- Comparison with TSH (2nd Gen): n = 218 samples.
- Comparison with ACS:180: n = 203 samples.
- Comparison with Elecsys: n = 56 samples.
The provenance of these samples (country of origin, retrospective/prospective) is not specified.
- Specificity (Cross-reactivity) Test: Normal human serum pools were used, spiked with the compounds. The number of pools or specific sample size beyond "pools" is not specified. Provenance is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- This device is an in vitro diagnostic (IVD) assay designed to provide quantitative measurements. For such devices, the "ground truth" for analytical performance (precision, accuracy, specificity) is typically established through reference methods, certified standards, or consensus values from established laboratory practices, rather than by human expert review of individual cases.
- The document does not mention the use of human experts to establish ground truth for the test set in the traditional sense of clinical adjudication. The ground truth for comparative studies is the result from the predicate devices or reference methods.
4. Adjudication Method for the Test Set
- Since the ground truth for this type of IVD performance study is based on analytical measurements (predicate device results, certified values, spiked samples), an "adjudication method" involving multiple human readers (e.g., 2+1, 3+1) is not applicable and not described in the document.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- An MRMC study is not applicable to this type of IVD device. The device does not involve human readers interpreting images or data; it provides a quantitative measurement. Therefore, no information on the effect size of human readers improving with AI vs. without AI assistance is present or relevant.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- This device is a standalone algorithm/assay (the "3rd Generation TSH Method"). The performance data presented (precision, correlation, specificity) is the standalone performance of the assay. There is no human-in-the-loop component for the measurement itself, though human interpretation of the results is part of the intended clinical use.
7. Type of Ground Truth Used
- For Precision: The ground truth is assumed to be the known concentration of commercially available controls or spiked samples used in the precision studies.
- For Correlation/Comparison: The ground truth is the measurement obtained from the predicate/established TSH assay methods (TSH (2nd Gen), Ciba-Corning ACS™ TSH-3, Boehringer-Mannheim Elecsys® TSH Assay).
- For Specificity: The ground truth is the known concentration of the spiked cross-reactant and the assumption that a highly specific assay should report negligible or no TSH value in the presence of these interfering substances.
8. Sample Size for the Training Set
- Details about a "training set" are not provided. Immunoassays typically do not involve machine learning models that require a separate, distinct "training set" in the same way AI algorithms do. The development process for an immunoassay involves extensive optimization and validation using various samples, but these are generally considered part of the assay development and analytical validation, not a distinct "training set" for an algorithm.
9. How the Ground Truth for the Training Set Was Established
- As a traditional immunoassay, the concept of a "training set" with established ground truth as it applies to AI/ML is not relevant or described. The ground truth for assay development would typically involve reference materials, spiked samples, and comparison to established methods or clinical samples with known TSH levels (e.g., hypothyroid, euthyroid, hyperthyroid). The document doesn't detail this developmental phase specifically.
{0}------------------------------------------------
JUN 5 1898
Summary of Safety and Effectiveness
3rd Generation TSH Method for the Bayer Immuno 1™ System
Listed below is a comparison of the performance of the Bayer Immuno 1™ 3rd Generation TSH (3Gen TSH) method and similar devices granted clearance of substantial equivalence (Bayer Immuno 1 TSH Assay, (Chiron) Ciba-Corning ACS™ TSH-3 Assay and (Roche) Boehringer-Mannheim Elecsys® TSH Assay). The information below was extracted from the Bayer Immuno 1 3rd Generation TSH method sheet and Package Inserts from the other three methods.
Intended Use
This in vitro diagnostic method is intended to quantitatively measure thyroid stimulating hormone (TSH) in human serum or plasma with 3d generation sensitivity on the Bayer Immuno 1 System. Measurements of TSH, produced by the anterior pituitary, are used in the diagnosis of thyroid or pituitary disorders.
| Bayer Corporation | Ciba-Corning | Boehringer-Mannheim | ||||||
|---|---|---|---|---|---|---|---|---|
| Bayer Immuno 1 | ACS:180 | Elecsys | ||||||
| 3GEN TSH | TSH | TSH-3 | TSH | |||||
| Part NumberReagentsCalibrators | T01-4038-51T03-4039-01 | T01-2942-51T03-3568-01 | 570056(rgnts and calibs) | 17314591731483 | ||||
| Expected Values | 0.31 - 4.7 µIU/mL | 0.47 - 6.9 µIU/mL | 0.35 - 5.5 µIU/mL | 0.25 - 4.2 µIU/mL | ||||
| Precision (within-run)(n = 20 over 10 days) | mean | % CV | mean | % CV | mean | % CV | mean | % CV |
| 0.008 | 12.6 | 0.1 | 8.0 | 0.026 | 10.7 | 0.084 | ||
| 0.019 | 4.1 | 1.3 | 5.5 | 0.077 | 6.5 | 0.091 | 2.1 | |
| 0.031 | 3.7 | 9.0 | 1.7 | 0.668 | 3.9 | 0.34 | 8.6 | |
| 0.50 | 4.0 | 22.5 | 1.6 | 4.81 | 3.3 | 2.45 | 1.9 | |
| 4.68 | 2.8 | 33.503 | 3.2 | 3.96 | 1.8 | |||
| 29.26 | 1.4 | 97.021 | 4.0 | 10.67 | 1.5 | |||
| 59.03 | 1.4 | |||||||
| Precision (total)(n = 20 over 10 days) | 0.008 | 12.6 | 0.1 | 13.0 | 0.026 | 15.8 | 0.084 | 5.4 |
| 0.019 | 5.1 | 1.3 | 6.3 | 0.077 | 8.4 | 0.091 | 3.3 | |
| 0.031 | 3.7 | 9.0 | 2.0 | 0.668 | 4.1 | 0.34 | 8.7 | |
| 0.50 | 4.2 | 22.5 | 1.8 | 4.810 | 3.5 | 2.45 | 2.2 | |
| 4.68 | 3.1 | 33.503 | 3.9 | 3.96 | 3.6 | |||
| 29.26 | 4.1 | 97.021 | 5.0 | 10.67 | 1.8 | |||
| 59.03 | 1.8 | |||||||
| Regression Equation | y = 0.980x - 0.011 | y = 0.928x - 0.021 | y = 0.988x - 0.122 | |||||
| where:y = | 3Gen TSH | |||||||
| x = | TSH (2nd Gen) | ACS:180 | Elecsys | |||||
| n = | 218 | 203 | 56 | |||||
| r = | 0.998 | 0.996 | 0.997 | |||||
| Sy.x = | 1.655 | 0.676 | 1.049 | |||||
| range = | 0.05 - 104.5 | 0.01 - 68.1 | 0.01 - 65.3 |
{1}------------------------------------------------
Specificity: Cross Reactants Spiked into Normal Human Serum Pools.
| Compound | Test Concentration(µIU/mL) | Crossreactivity(%) |
|---|---|---|
| human Chorionic Gonadotropin (hCG) | 250,000 | < 0.001 |
| Leutinizing Hormone (LH) | 2,000 | < 0.001 |
| Follicle Stimulating Hormone (FSH) | 2,000 | < 0.001 |
Gabriel J. Muraca Jr.
Gabriel J. Muraca, Jr.
Gabriel J. Muraca, Jr. Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097
4/6/98
Date
{2}------------------------------------------------
Image /page/2/Picture/1 description: The image shows the words "Public Health Service" in bold, black font. The words are stacked on top of each other, with "Public Health" on the first line and "Service" on the second line. The text appears to be extracted from a document or sign.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
2 1898 JUN
Gabriel Muraca, Jr. Manager Regulatory Affairs Baver Corporation 511 Benedict Avenue 10591-5097 Tarrytown, New York
K981312 Re: 3rd Generation TSH Assay for the Bayer Immuno 1™ System Regulatory Class: I & II Product Code: JLW, JIS, JJX April 7, 1998 Dated: Received: April 10, 1998
Dear Mr. Muraca:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major requlations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Reqister. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
{3}------------------------------------------------
Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".
Sincerely yours,
Steven Gutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
{4}------------------------------------------------
Page 1 of 1
510(k) Number (if known): K981312
Baver Immuno 1™ System Device Name: 3rd Generation Thyroid Stimulating Hormone (TSH) Assay
Indications For Use:
This in vitro diagnostic method is intended to quantitatively measure thyroid stimulating hormone in human serum or plasma on the Bayer Immuno 1 System. Measurements of TSH, with a 3td Generation sensitivity of <20% total CV at 0.01 uIUmL to 0.02 µIU/mL (as defined by the American Thyroid Association), are used as an aid in the diagnosis of thyroid or pituitary disorders.
This diagnostic method is not intended for use on any other system.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use __
Optional Format 1-2-96
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K981312
§ 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.