Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard in vitro diagnostic immunoassay for measuring TSH levels. There is no mention of AI, ML, image processing, or any other technology typically associated with AI/ML applications in medical devices. The performance studies are based on standard analytical validation methods for IVD assays.

Therapeutic

No.
This device is an in vitro diagnostic assay used for the quantitative determination of thyroid-stimulating hormone (TSH) to aid in the diagnosis of thyroid or pituitary disorders. It does not provide treatment or therapy.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states that the assay is for "in vitro diagnostic use" and that "Measurements of thyroid stimulating hormone... are used in the diagnosis of thyroid or pituitary disorders."

SaMD (Software as a Medical Device)

No

The device is an in vitro diagnostic assay, which involves chemical reagents and is used with a specific hardware system (ADVIA Centaur® XP system), indicating it is not a software-only medical device.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "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..."

This statement clearly identifies the device as being intended for use outside of the body to examine specimens from the human body for the purpose of providing information for the diagnosis of thyroid or pituitary disorders. This aligns directly with the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for 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 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.

Product codes

JLW

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.

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

Not Found

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

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

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	Mean µIU/mL (mIU/L)	Repeatability SDb µIU/mL (mIU/L)	CVc (%)	Within-Laboratory Precision SD µIU/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
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

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

Concentration Interval	Precision 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).

Sample	Mean µIU/mL (mIU/L)	Repeatability SDª µIU/mL (mIU/L)	CVᵇ (%)	Between Day SD µIU/mL (mIU/L)	CV (%)	Between Lot SD µIU/mL (mIU/L)	CV (%)	Between Instrument SD µIU/mL (mIU/L)	CV (%)	Reproducibility SD µIU/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

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.

Sample	Comparative Assay (x)	Regression Equation	Sample Interval	Na	rb
Serum	ADVIA Centaur TSH3-UL assay using the ADVIA Centaur XP system	y = 0.97x - 0.007 µIU/mL	0.012-147.3 µIU/mL	973	0.999
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 µIU/mL	0.050-147.805 µIU/mL	52	0.999
Plasma, lithium heparin	y = 1.01x - 0.034 µIU/mL	0.115-135.881 µIU/mL	57	0.990
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) and 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 a TSH concentration of approximately 0.900 µIU/mL (mIU/L) and 8.000 µIU/mL (mIU/L).

Substance	Substance Test Concentration	Substance	Substance Test Concentration
Hemoglobin	500 mg/dL (5.00 g/L)	Acetaminophen	15.6 mg/dL (1033 µmol/L)
Bilirubin, conjugated	40 mg/dL (474 µmol/L)	Liothyronine	0.0075 mg/dL (0.116 µmol/L)
Bilirubin, unconjugated	40 mg/dL (684 µmol/L)	Methimazole	8.0 mg/dL (701 µmol/L)
Lipemia (Intralipid)	1000 mg/dL (11.3 mmol/L)	Methyldopa	2.25 mg/dL (107 µmol/L)
Acetylsalicylic acid	3.0 mg/dL (167 µmol/L)	Metronidazole	12.3 mg/dL (719 µmol/L)
Ampicillin	7.5 mg/dL (215 µmol/L)	N-Acetylcysteine	15.0 mg/dL (920 µmol/L)
Ascorbic Acid	5.25 mg/dL (298 µmol/L)	Octreotide	0.03 mg/dL (0.294 µmol/L)
Biotin	0.35 mg/dL (14.3 µmol/L)	Phenylbutazone	32.1 mg/dL (1040 µmol/L)
Carbimazole	3.0 mg/dL (161 µmol/L)	Propranolol	24 mg/dL (926 µmol/L)
Cefoxitin	495 mg/dL (11583 µmol/L)	Propylthiouracil	30 mg/dL (1762 µmol/L)
Cholesterol	400 mg/dL (10.3 mmol/L)	Rheumatoid Factor	1500 IU/mL
Cyclosporine	0.18 mg/dL (1.50 µmol/L)	Rifampicin	4.8 mg/dL (58.6 µmol/L)
Doxycycline	1.8 mg/dL (40.5 µmol/L)	Theophylline	6.0 mg/dL (333 µmol/L)
Heparin	7500 U/dL	Total Protein	15 g/dL (150 g/L)
Ibuprofen	21.9 mg/dL (1062 µmol/L)
Levodopa	0.75 mg/dL (38.0 µmol/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

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.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s)

K083844, K150403

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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.

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).

1

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

2

Indications for Use

510(k) Number (if known) K233050

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

Indications for Use (Describe)

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.

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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3

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

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.

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

4

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-Ultra
K083844/K150403 |
|---------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------|
| Intended Use / Indications for
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 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. | 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 antibody
BSA conjugate labeled with acridinium
ester | Same |
| Solid Phase Antibody | FITC-labeled mouse monoclonal anti-TSH
antibody and mouse monoclonal anti-
fluorescein antibody linked to
paramagnetic particles | Mouse monoclonal anti-fluorescein
antibody linked to
paramagnetic particles |
| Ancillary Antibody | FITC conjugated to mouse monoclonal
anti-TSH antibody | Same |
| Sample Volume | 100 µL | Same |
| Calibrator | After reconstitution, TSH (human); buffer;
equine serum; sodium azide ( 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:

7

| | | Repeatability | | Between Day | | Between Lot | | Between
Instrument | | Reproducibility | |
|-----------|---------------------------|--------------------------|------------|-------------------------|-----------|-------------------------|-----------|-------------------------|-----------|-------------------------|-----------|
| Sample | Mean
µIU/mL
(mIU/L) | SDª
µIU/mL
(mIU/L) | CVᵇ
(%) | SD
µIU/mL
(mIU/L) | CV
(%) | SD
µIU/mL
(mIU/L) | CV
(%) | SD
µIU/mL
(mIU/L) | CV
(%) | SD
µIU/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 using
the 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)

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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

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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.