The ADVIA Centaur® TSH3-Ultra II (TSH3ULII) assay is for in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in human serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur® XP system. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

Device Description

This assay is a third-generation assay that employs anti-FITC monoclonal antibody covalently bound to paramagnetic particles, an FITC-labeled anti-TSH capture mouse monoclonal antibody, and a tracer consisting of a proprietary acridinium ester and an anti-TSH mouse monoclonal antibody conjugated to bovine serum albumin (BSA) for chemiluminescent detection.

AI/ML Overview

The provided text describes the ADVIA Centaur® TSH3-Ultra II (TSH3ULII) assay, a device for in vitro diagnostic quantitative determination of thyroid-stimulating hormone (TSH). The document covers the device's indications for use, comparison with a predicate device, and performance characteristics data.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (Design Goal)	Reported Device Performance
Detection Capability	N/A (LoB, LoD, LoQ are reported values, not acceptance criteria for determination)	- Limit of Blank (LoB): 0.005 µIU/mL (mIU/L) - Limit of Detection (LoD): 0.008 µIU/mL (mIU/L) - Limit of Quantitation (LoQ): 0.010 µIU/mL (mIU/L) (Lower than predicate device's LoQ of 0.008 µIU/mL, but within acceptable range for the new device as specified in assay range)
Precision	- Repeatability (Within-Run): - ≤ 12% CV for 0.020–0.299 µIU/mL (mIU/L) - ≤ 6% CV for ≥ 0.300–90.000 µIU/mL (mIU/L) - ≤ 7% CV for > 90.000 µIU/mL (mIU/L) - Within-Laboratory (Total Precision): - ≤ 16% CV for 0.020–0.299 µIU/mL (mIU/L) - ≤ 8% CV for ≥ 0.300–90.000 µIU/mL (mIU/L) - ≤ 10% CV for > 90.000 µIU/mL (mIU/L)	Reported values (all calculated Repeatability CV and Within-Laboratory CV values are within the specified limits): - Serum A (0.088 µIU/mL): Repeatability CV 2.5%, Within-Lab CV 3.6% - Serum B (0.196 µIU/mL): Repeatability CV 1.8%, Within-Lab CV 3.1% - Serum C (0.507 µIU/mL): Repeatability CV 1.7%, Within-Lab CV 2.6% - Serum D (4.752 µIU/mL): Repeatability CV 2.3%, Within-Lab CV 2.7% - Serum E (46.749 µIU/mL): Repeatability CV 2.4%, Within-Lab CV 4.0% - Serum F (97.929 µIU/mL): Repeatability CV 2.2%, Within-Lab CV 3.5% Similar acceptable results for Plasma and Controls.
Reproducibility	- Reproducibility (Total): - ≤ 18.5% CV for 0.020-0.299 µIU/mL (mIU/L) - ≤ 10.5% CV for ≥ 0.300-90.000 µIU/mL (mIU/L) - ≤ 12.5% CV for > 90.000 µIU/mL (mIU/L)	Reported values (all calculated Reproducibility CV values are within the specified limits): - Serum A (0.090 µIU/mL): Reproducibility CV 3.11% - Serum B (0.178 µIU/mL): Reproducibility CV 4.87% - Serum C (0.474 µIU/mL): Reproducibility CV 2.21% - Serum D (4.684 µIU/mL): Reproducibility CV 2.47% - Serum E (56.562 µIU/mL): Reproducibility CV 2.33% - Serum F (99.522 µIU/mL): Reproducibility CV 4.12% Similar acceptable results for Plasma and Controls.
Assay Comparison	- Correlation coefficient (r) ≥ 0.95 - Slope of 1.0 ± 0.1	- Correlation coefficient (r): 0.999 - Regression Equation (Slope): 0.97 (within 1.0 ± 0.1)
Specimen Equivalency	- Correlation coefficient (r) ≥ 0.95 - Slope of 0.95-1.05	- Plasma, EDTA vs. Serum: r = 0.999, Slope = 0.99 (within 0.95-1.05) - Plasma, lithium heparin vs. Serum: r = 0.990, Slope = 1.01 (within 0.95-1.05)
Interferences (HIL)	Bias due to hemoglobin, bilirubin (conjugated/unconjugated), and Intralipid does not exceed 10%	Hemoglobin (500mg/dL), Bilirubin (40mg/dL), Intralipid (1000mg/dL) do not exceed 10% bias at TSH concentrations of ~0.900 µIU/mL and ~8.000 µIU/mL.
Interferences (Other Substances)	Bias due to various common substances does not exceed 10%	Various substances (e.g., Acetaminophen, Aspirin, Biotin, Heparin, Ibuprofen, Levothyroxine) at specified concentrations do not exceed 10% bias at TSH concentrations of ~0.900 µIU/mL and ~8.000 µIU/mL.
Cross-Reactivity	Cross-reactivity of hCG, FSH, and LH does not exceed 5%	hCG (200000 mIU/mL), FSH (1500 mIU/mL), LH (600 mIU/mL) at specified concentrations do not exceed 5% cross-reactivity at TSH concentrations of ~0.400, 5.00, 17.00, and 90.00 µIU/mL.
Linearity	Device is linear throughout its measuring interval (0.010–150.000 µIU/mL)	"The assay is linear for the measuring interval of 0.010–150.000 µIU/mL (mIU/L)."
High-Dose Hook Effect	Results for TSH concentrations above the measuring interval and up to 3000 µIU/mL should report > 150 µIU/mL (not a paradoxical decrease)	"Patient samples with TSH concentrations above the measuring interval and as high as 3000 µIU/mL will report > 150 µIU/mL (mIU/L)." (This confirms the absence of a significant high-dose hook effect within this specified range, meaning the device displays the result as above the measurable range.)

The study that proves the device meets the acceptance criteria is detailed across the "Performance Characteristics Data" section (Section 8) of the 510(k) Summary.

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

Detection Capability (LoQ): Not specified (CLSI Document EP17-A2 was followed).
Precision: 80 measurements (replicates of 2, 2 runs/day, 20-day protocol) for each of the 6 serum samples, 5 plasma samples, and 5 control samples. Total N for Precision study is 80 x (6+5+5) = 1280 measurements.
Reproducibility: 225 measurements (replicates of 5, 1 run/day, 5-day protocol) for each of the 6 serum samples, 5 plasma samples, and 5 control samples. Total N for Reproducibility study is 225 x (6+5+5) = 3600 measurements.
Assay Comparison: 973 samples.
Specimen Equivalency:
- Plasma, EDTA vs. Serum: 52 samples.
- Plasma, lithium heparin vs. Serum: 57 samples.
Interferences (HIL and Other Substances): Samples at two TSH concentrations (~0.900 µIU/mL and ~8.000 µIU/mL) were tested for each interfering substance. The exact number of individual samples tested is not given, but multiple samples would be required for the two TSH levels per substance.
Cross-Reactivity: Samples at four TSH concentrations (~0.400, 5.00, 17.00, and 90.00 µIU/mL) were spiked with hCG, FSH, or LH. The exact number of individual samples is not given.
Linearity: Not explicitly stated, but performed in accordance with CLSI Document EP06-ed2, which involves testing multiple diluted samples.
High-Dose Hook Effect: Samples with TSH concentrations up to 3000 µIU/mL were evaluated. The number of samples tested is not explicitly stated.

Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given it's an in vitro diagnostic device, the samples would generally be human biological specimens, likely collected from a clinical laboratory setting. The use of CLSI documents (Clinical and Laboratory Standards Institute) suggests standard laboratory practices.

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

This information is not provided in the document. For an in vitro diagnostic assay like TSH, "ground truth" is typically established by:

The reference method against which the new assay is compared (for accuracy/assay comparison). In this case, "ADVIA Centaur TSH3-UL assay" is used as the comparative assay (the predicate device).
Traceability to an international standard (WHO 3rd International Reference Preparation for human TSH (IRP 81/565)), which implies that the TSH values are calibrated against a universally accepted standard, rather than expert consensus on individual patient cases.

4. Adjudication Method for the Test Set

This refers to the process of resolving discrepancies in expert opinions, which is not applicable here as it is an analytical performance study for an IVD, not an interpretative AI device requiring human expert label agreement.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for AI-assisted diagnostic imaging devices where human readers interpret medical images with and without AI assistance. This document pertains to an in vitro diagnostic assay, which involves automated quantitative measurement of a biomarker.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, implicitly. The entire performance characterization (Detection Capability, Precision, Reproducibility, Assay Comparison, Specimen Equivalency, Interferences, Cross-Reactivity, Linearity, High-Dose Hook Effect) is describing the standalone performance of the TSH3-Ultra II assay as an automated laboratory test. There is no mention of "human-in-the-loop" for this device's intended diagnostic function.

7. Type of Ground Truth Used

The ground truth for the performance studies is established by:

Reference materials/standards: For accuracy, the assay is traceable to the World Health Organization (WHO) 3rd International Reference Preparation for human TSH (IRP 81/565).
Comparative method: For assay comparison, the predicate device (ADVIA Centaur TSH3-UL assay) results serve as the comparative standard.
Defined concentrations: For precision, linearity, interferences, and cross-reactivity, samples with known or spiked concentrations of TSH or interfering substances are used.

8. Sample Size for the Training Set

The document does not report a training set sample size. This is because the ADVIA Centaur TSH3-Ultra II is a chemical immunoassay, not a machine learning or AI-based device that would typically involve a "training set" in the computational sense. The "development" process for such an assay involves reagent formulation, assay optimization, and calibration curve development, which are distinct from training an AI model.

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

As there is no "training set" in the context of an AI/ML model, this question is not applicable. The assay's analytical characteristics are established through various studies (precision, accuracy, linearity, etc.) using calibrated materials and established reference methods, as detailed in the performance characteristics.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo in blue, with the words "U.S. FOOD & DRUG" on top and "ADMINISTRATION" on the bottom.

April 4, 2024

Siemens Healthcare Diagnostics, Inc. Kelly Scuderi Regulatory Affairs Professional 511 Benedict Avenue Tarrytown, New York 10591

Re: K233050

Trade/Device Name: ADVIA Centaur® TSH3-Ultra II (TSH3ULII) Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid Stimulating Hormone Test System Regulatory Class: Class II Product Code: JLW Dated: March 1, 2024 Received: March 1, 2024

Dear Kelly Scuderi:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Paula V. Caposino -S

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known) K233050

Device Name ADVIA Centaur® TSH3-Ultra II (TSH3ULII)

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

510(k) Summary of Safety and Effectiveness

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

The assigned 510(k) number is: K233050

1. Applicant

Siemens Healthcare Diagnostics, Inc. 511 Benedict Avenue Tarrytown, NY 10591 USA

Contact: Kelly Scuderi Requlatory Affairs Professional Title: E-mail: kelly.scuderi@siemens-healthineers.com Phone: 781-856-6516

Date of Preparation: September 25, 2023

2. Device

Requlatory Information

Device Name:	ADVIA Centaur® TSH3-Ultra II (TSH3ULII)
Classification Name:	Thyroid stimulating hormone test system
Regulation Number:	21 CFR 862.1690
Classification:	Class II
Product Code:	JLW
Review Panel:	Clinical Chemistry

3. Predicate Device

The predicate device, ADVIA Centaur® TSH3-Ultra manufactured by Siemens Healthcare Diagnostics, Inc. Tarrytown, NY USA, was cleared by the FDA under K083844 and K150403.

4. Device Description

5. Intended Use

The ADVIA Centaur® TSH3-Ultra II (TSH3ULII) assay is for in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in human serum

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and plasma (EDTA and lithium heparin) using the ADVIA Centaur® XP system. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

6. Indications for Use

Same as Intended use.

7. Comparison of Technological Characteristics with the Predicate Device

The following table provides a comparison between the predicate and candidate device.

Attribute	Candidate Device:ADVIA Centaur TSH3-Ultra II(TSH3ULII)	Predicate Device:ADVIA Centaur TSH3-UltraK083844/K150403
Intended Use / Indications forUse	The ADVIA Centaur TSH3-Ultra II(TSH3ULII) assay is for in vitro diagnosticuse in the quantitative determination ofthyroid-stimulating hormone (TSH,thyrotropin) in human serum and plasma(EDTA and lithium heparin) using theADVIA Centaur® XP system.Measurements of thyroid stimulatinghormone produced by the anteriorpituitary are used in the diagnosis ofthyroid or pituitary disorders.	Same
Analyte	TSH	Same
Automated	Automated assay	Same
Measurement	Quantitative	Same
Sample Type	Human serum and plasma	Same
Detection Limit	LoQ: 0.010 µIU/mL (mIU/L)	LoQ: 0.008 µIU/mL (mIU/L)
Assay Range	0.010-150.000 µIU/mL (mIU/L)	0.008–150 µIU/mL (mIU/L)
Operating Principle	Immunologic sandwich	Same
Technology	Direct chemiluminescent	Same
Lite Reagent Antibody	Mouse monoclonal anti-TSH antibodyBSA conjugate labeled with acridiniumester	Same
Solid Phase Antibody	FITC-labeled mouse monoclonal anti-TSHantibody and mouse monoclonal anti-fluorescein antibody linked toparamagnetic particles	Mouse monoclonal anti-fluoresceinantibody linked toparamagnetic particles
Ancillary Antibody	FITC conjugated to mouse monoclonalanti-TSH antibody	Same
Sample Volume	100 µL	Same
Calibrator	After reconstitution, TSH (human); buffer;equine serum; sodium azide (< 0.1%);stabilizers; preservatives	Same
Number of Calibrators	2	Same
Calibrators Packaging	Provided with reagent kit	Same
Use of Controls	Yes (recommended)	Same
Traceability	Traceable to the World HealthOrganization (WHO) 3rd InternationalReference Preparation for human TSH(IRP 81/565)	Same

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8. Performance Characteristics Data

Detection Capability

Limit of Blank (LoB) 0.005 µIU/mL (mIU/L) Limit of Detection (LoD) 0.008 µlU/mL (mIU/L) Limit of Quantitation (LoQ) 0.010 µlU/mL (mIU/L)

Detection capability was determined in accordance with CLSI Document EP17-A2.

The LoB corresponds to the highest measurement result likely to be observed for a blank sample with a probability of 95%. The LoD corresponds to the lowest analyte concentration that can be detected with a probability of 95%. The LoQ corresponds to the lowest analyte concentration at which the within laboratory CV is ≤ 20%.

Precision

Precision was determined in accordance with CLSI Document EP05-A3. Samples were assayed in replicates of 2 with 2 runs per day using a 20-day protocol.

Sample	Na	MeanµIU/mL (mIU/L)	Repeatability		Within-Laboratory Precision
			SDbµIU/mL (mIU/L)	CVc(%)	SDµIU/mL (mIU/L)	CV(%)
Serum A	80	0.088	0.0022	2.5	0.0032	3.6
Serum B	80	0.196	0.0035	1.8	0.0062	3.1
Serum C	80	0.507	0.0086	1.7	0.0134	2.6
Serum D	80	4.752	0.1083	2.3	0.1293	2.7
Serum E	80	46.749	1.1297	2.4	1.8749	4.0
Serum F	80	97.929	2.1282	2.2	3.4288	3.5
Plasma, lithium heparin A	80	0.099	0.0014	1.4	0.0029	2.9
Plasma, lithium heparin B	80	0.520	0.0089	1.7	0.0175	3.4
Plasma, lithium heparin C	80	4.908	0.0763	1.6	0.1139	2.3
Plasma, lithium heparin D	80	53.262	0.7579	1.4	1.5032	2.8

The following results are representative of the performance of the assay:

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			Repeatability		Within-Laboratory Precision
Sample	Na	MeanµIU/mL (mIU/L)	SDbµIU/mL (mIU/L)	CVc(%)	SDµIU/mL (mIU/L)	CV(%)
Plasma, lithium heparin E	80	91.993	3.2754	3.6	5.7348	6.2
Control 1	80	0.104	0.0021	2.1	0.0035	3.4
Control 2	80	0.516	0.0087	1.7	0.0203	3.9
Control 3	80	4.778	0.0811	1.7	0.1316	2.8
Control 4	80	47.494	0.6508	1.4	1.7552	3.7
Control 5	80	99.366	1.5194	1.5	2.9443	3.0

a Number of measurements.

b Standard deviation.

Coefficient of variation.

The assay was designed to have the following precision when using a 20-day protocol in accordance with CLSI Document EP05-A3:

	Precision
Concentration Interval	Repeatability (Within-Run)	Within-Laboratory (Total Precision)
0.020–0.299 µIU/mL (mIU/L)	≤ 12% CV	≤ 16% CV
≥ 0.300–90.000 µIU/mL (mIU/L)	≤ 6% CV	≤ 8% CV
> 90.000 µIU/mL (mIU/L)	≤ 7% CV	≤ 10% CV

Reproducibility

Reproducibility was determined in accordance with CLSI Document EP05-A3. Testing was performed using 3 instruments and 3 reagent lots. Samples were assayed in replicates of 5 with 1 run per day using a 5-day protocol (225 measurements per sample).

The following results are representative of the performance of the assay:

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		Repeatability		Between Day		Between Lot		BetweenInstrument		Reproducibility
Sample	MeanµIU/mL(mIU/L)	SDªµIU/mL(mIU/L)	CVᵇ(%)	SDµIU/mL(mIU/L)	CV(%)	SDµIU/mL(mIU/L)	CV(%)	SDµIU/mL(mIU/L)	CV(%)	SDµIU/mL(mIU/L)	CV(%)
Serum A	0.090	0.002	1.99	0.001	1.41	0.002	1.80	0.001	0.67	0.003	3.11
Serum B	0.178	0.008	4.73	0.002	0.91	0.001	0.70	0.000	0.22	0.009	4.87
Serum C	0.474	0.007	1.47	0.005	0.95	0.006	1.34	0.000	0.00	0.010	2.21
Serum D	4.684	0.075	1.61	0.061	1.29	0.062	1.32	0.015	0.32	0.116	2.47
Serum E	56.562	0.953	1.68	0.539	0.95	0.337	0.60	0.649	1.15	1.316	2.33
Serum F	99.522	2.118	2.13	1.101	1.11	2.448	2.46	2.254	2.26	4.095	4.12
Plasma A	0.093	0.002	2.17	0.001	1.42	0.001	1.50	0.000	0.44	0.003	3.03
Plasma B	0.436	0.011	2.63	0.007	1.72	0.005	1.11	0.003	0.71	0.015	3.40
Plasma C	4.490	0.115	2.55	0.103	2.30	0.043	0.96	0.036	0.80	0.164	3.66
Plasma D	49.569	1.129	2.28	1.275	2.57	0.305	0.62	1.212	2.44	2.112	4.26
Plasma E	102.084	1.879	1.84	1.202	1.18	0.502	0.49	2.239	2.19	3.200	3.13
Control 1	0.103	0.002	2.03	0.001	0.75	0.002	1.79	0.001	1.01	0.003	2.98
Control 2	0.516	0.007	1.38	0.004	0.82	0.007	1.36	0.000	0.00	0.011	2.10
Control 3	4.716	0.069	1.47	0.036	0.76	0.065	1.37	0.000	0.00	0.101	2.15
Control 4	47.003	0.712	1.52	0.572	1.22	0.272	0.58	0.521	1.11	1.086	2.31
Control 5	99.051	1.790	1.81	2.111	2.13	0.000	0.00	1.930	1.95	3.374	3.41

a Standard deviation.

b Coefficient of variation.

The assay was designed to have the following reproducibility when using a 5-day protocol in accordance with CLSI Document EP05-A3:

Concentration Interval	Reproducibility
0.020-0.299 µIU/mL (mIU/L)	≤ 18.5% CV
≥ 0.300-90.000 µIU/mL (mIU/L)	≤ 10.5% CV
> 90.000 µIU/mL (mIU/L)	≤ 12.5% CV

Assay Comparison

Assay comparison was determined with the Passing-Bablok regression model in accordance with CLSI Document EP09c-ed3.

Agreement of the assays may vary depending on the study design, comparative assay, and population tested.

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Sample	Comparative Assay (x)	Regression Equation	Sample Interval	Na	rb
Serum	ADVIA Centaur TSH3-UL assay usingthe ADVIA Centaur XP system	$y = 0.97x - 0.007 \muIU/mL$	0.012-147.3 $\muIU/mL$	973	0.999

a Number of samples tested.

b Correlation coefficient.

The assay is designed to have a correlation coefficient of ≥ 0.95 and a slope of 1.0 ± 0.1.

Specimen Equivalency

Specimen equivalency was determined with the Passing-Bablok regression model using the ADVIA Centaur XP system in accordance with CLSI Document EP09c-ed3.

Agreement of the specimen types may vary depending on the study design and population tested.

Tube (y) vs. Serum (x)	Regression Equation	Sample Interval	Na	rb
Plasma, EDTA	$y = 0.99x - 0.019 \mu IU/mL$	0.050-147.805 $\mu$ IU/mL	52	0.999
Plasma, lithium heparin	$y = 1.01x - 0.034 \mu IU/mL$	0.115-135.881 $\mu$ IU/mL	57	0.990

a Number of samples tested.

b Correlation coefficient.

The assay is designed to have a correlation coefficient of ≥ 0.95 and a slope of 0.95-1.05.

Interferences

Hemolysis, Icterus, Lipemia (HIL):

Interference testing was performed using the ADVIA Centaur XP system in accordance with CLSI Document EP07-ed3.

The following substances do not interfere with the assay when present in serum at the concentrations indicated. Bias due to these substances does not exceed 10% at a TSH concentration of approximately 0.900 µIU/mL (mIU/L) and 8.000 µIU/mL (mIU/L).

Substance	Substance Test Concentration
Hemoglobin	500 mg/dL (5.00 g/L)
Bilirubin, conjugated	40 mg/dL (474 $\mu$ mol/L)
Bilirubin, unconjugated	40 mg/dL (684 $\mu$ mol/L)
Lipemia (Intralipid)	1000 mg/dL (11.3 mmol/L)

{9}------------------------------------------------

Other Substances:

Interference testing was performed using the ADVIA Centaur XP system in accordance with CLSI Document EP07-ed3.

The following substances do not interfere with the assay when present in serum at the concentrations indicated. Bias due to these substances does not exceed 10% at TSH concentrations of approximately 0.900 µIU/mL (mIU/L) and 8.000 µIU/mL (mIU/L).

Substance	Substance Test Concentration	Substance	Substance Test Concentration
Acetaminophen	15.6 mg/dL (1033 µmol/L)	Liothyronine	0.0075 mg/dL (0.116 µmol/L)
Acetylsalicylic acid	3.0 mg/dL (167 µmol/L)	Methimazole	8.0 mg/dL (701 µmol/L)
Ampicillin	7.5 mg/dL (215 µmol/L)	Methyldopa	2.25 mg/dL (107 µmol/L)
Ascorbic Acid	5.25 mg/dL (298 µmol/L)	Metronidazole	12.3 mg/dL (719 µmol/L)
Biotin	0.35 mg/dL (14.3 µmol/L)	N-Acetylcysteine	15.0 mg/dL (920 µmol/L)
Carbimazole	3.0 mg/dL (161 µmol/L)	Octreotide	0.03 mg/dL (0.294 µmol/L)
Cefoxitin	495 mg/dL (11583 µmol/L)	Phenylbutazone	32.1 mg/dL (1040 µmol/L)
Cholesterol	400 mg/dL (10.3 mmol/L)	Propranolol	24 mg/dL (926 µmol/L)
Cyclosporine	0.18 mg/dL (1.50 µmol/L)	Propylthiouracil	30 mg/dL (1762 µmol/L)
Doxycycline	1.8 mg/dL (40.5 µmol/L)	Rheumatoid Factor	1500 IU/mL
Heparin	7500 U/dL	Rifampicin	4.8 mg/dL (58.6 µmol/L)
Ibuprofen	21.9 mg/dL (1062 µmol/L)	Theophylline	6.0 mg/dL (333 µmol/L)
Levodopa	0.75 mg/dL (38.0 µmol/L)	Total Protein	15 g/dL (150 g/L)
Levothyroxine	0.0429 mg/dL (0.552 µmol/L)

Cross-Reactivity

Cross-reactivity was determined using the ADVIA Centaur XP system in accordance with CLSI Document EP07-ed3.21 Cross-reactivity of samples spiked with various substances does not exceed 5% at TSH concentrations of approximately 0.400 µIU/mL (mIU/L), 5.00 µIU/mL (mIU/L), 17.00 µIU/mL (mIU/L), and 90.00 µIU/mL (mIU/L).

Substance	Substance Test Concentration
hCG	200000 mIU/mL
FSH	1500 mIU/mL
LH	600 mIU/mL

{10}------------------------------------------------

Linearity

Linearity testing was performed in accordance with CLSI Document EP06-ed2.

The assay is linear for the measuring interval of 0.010–150.000 µlU/mL (mIU/L).

High-Dose Hook Effect

High TSH concentrations can cause a paradoxical decrease in the RLUs (high-dose hook effect). In this assay, patient samples with TSH concentrations above the measuring interval and as high as 3000 µlU/mL will report > 150 µlU/mL (mlU/L).

Standardization

The assay standardization is traceable to the World Health Organization (WHO) 3rd International Reference Preparation for human TSH (IRP 81/565).

Assigned values for calibrators are traceable to this standardization.

9. Conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Regulation Number and Section

§ 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.