ADVIA Centaur® TSH3-Ultra II (TSH3ULII)

K233050 · Siemens Healthcare Diagnostics, Inc. · JLW · Apr 4, 2024 · Clinical Chemistry

Device Facts

• Record ID: K233050
• Device Name: ADVIA Centaur® TSH3-Ultra II (TSH3ULII)
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: JLW · Clinical Chemistry
• Decision Date: Apr 4, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1690
• Device Class: Class 2
• Attributes: Pediatric

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 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 Story

The ADVIA Centaur TSH3-Ultra II is an automated, third-generation in vitro diagnostic assay for quantitative TSH measurement. It utilizes an immunologic sandwich principle with direct chemiluminescent detection on the ADVIA Centaur XP system. Input samples consist of human serum or plasma (EDTA/lithium heparin). The assay employs paramagnetic particles coated with anti-fluorescein antibodies, an FITC-labeled anti-TSH capture antibody, and a tracer antibody conjugated to acridinium ester and BSA. The system processes these components to produce a chemiluminescent signal proportional to TSH concentration. Used in clinical laboratories, the device provides quantitative results to physicians to assist in diagnosing thyroid or pituitary dysfunction. The assay is standardized to the WHO 3rd IRP 81/565.

Clinical Evidence

Bench testing only. Precision studies (repeatability/within-lab) performed per CLSI EP05-A3; linearity per CLSI EP06; interference/cross-reactivity per CLSI EP07; detection limits (LoB/LoD/LoQ) per CLSI EP17-A2. Method comparison against predicate (N=404) showed slope 0.948, r=0.999. Matrix comparison (serum vs. EDTA/lithium heparin) showed high correlation (r≥0.990). No clinical studies were required.

Technological Characteristics

Direct chemiluminescent immunoassay; immunologic sandwich principle. Solid phase: paramagnetic particles with anti-fluorescein and FITC-labeled anti-TSH antibodies. Tracer: acridinium ester-labeled anti-TSH antibody. Automated system (ADVIA Centaur XP). Traceable to WHO 3rd IRP 81/565. Measuring range: 0.010–150.000 µIU/mL. Sample volume: 100 µL.

Indications for Use

Indicated for the quantitative determination of TSH in human serum and plasma (EDTA and lithium heparin) to aid in the diagnosis of thyroid or pituitary disorders in patients.

Regulatory Classification

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.

Predicate Devices

• ADVIA Centaur® TSH3-Ultra (K083844, K150403)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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)

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) | |
|-------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|
| <label><input checked="" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D)</label> | <label><input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C)</label> |

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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: [e-mail] Phone: [phone]

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

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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:<br>ADVIA Centaur TSH3-Ultra II<br>(TSH3ULII) | Predicate Device:<br>ADVIA Centaur TSH3-Ultra<br>K083844/K150403 |
|---------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------|
| Intended Use / Indications for<br>Use | The ADVIA Centaur TSH3-Ultra II<br>(TSH3ULII) assay is for <i>in vitro</i> diagnostic<br>use in the quantitative determination of<br>thyroid-stimulating hormone (TSH,<br>thyrotropin) in human serum and plasma<br>(EDTA and lithium heparin) using the<br>ADVIA Centaur® XP system.<br>Measurements of thyroid stimulating<br>hormone produced by the anterior<br>pituitary are used in the diagnosis of<br>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<br>BSA conjugate labeled with acridinium<br>ester | Same |
| Solid Phase Antibody | FITC-labeled mouse monoclonal anti-TSH<br>antibody and mouse monoclonal anti-<br>fluorescein antibody linked to<br>paramagnetic particles | Mouse monoclonal anti-fluorescein<br>antibody linked to<br>paramagnetic particles |
| Ancillary Antibody | FITC conjugated to mouse monoclonal<br>anti-TSH antibody | Same |
| Sample Volume | 100 µL | Same |
| Calibrator | After reconstitution, TSH (human); buffer;<br>equine serum; sodium azide (< 0.1%);<br>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 Health<br>Organization (WHO) 3rd International<br>Reference Preparation for human TSH<br>(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 | Mean<br>µIU/mL (mIU/L) | Repeatability | | Within-Laboratory Precision | |
|---------------------------|----|------------------------|-----------------------|------------|-----------------------------|-----------|
| | | | SDb<br>µIU/mL (mIU/L) | CVc<br>(%) | SD<br>µIU/mL (mIU/L) | CV<br>(%) |
| 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 | Mean<br>µIU/mL (mIU/L) | SDb<br>µIU/mL (mIU/L) | CVc<br>(%) | SD<br>µIU/mL (mIU/L) | CV<br>(%) |
| 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 | | Between<br>Instrument | | Reproducibility | |
|-----------|---------------------------|--------------------------|------------|-------------------------|-----------|-------------------------|-----------|-------------------------|-----------|-------------------------|-----------|
| Sample | Mean<br>µIU/mL<br>(mIU/L) | SDª<br>µIU/mL<br>(mIU/L) | CVᵇ<br>(%) | SD<br>µIU/mL<br>(mIU/L) | CV<br>(%) | SD<br>µIU/mL<br>(mIU/L) | CV<br>(%) | SD<br>µIU/mL<br>(mIU/L) | CV<br>(%) | SD<br>µIU/mL<br>(mIU/L) | CV<br>(%) |
| 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<br>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.