ADVIA Centaur TSH3-Ultra

K150403 · Siemens Healthcare Diagnostics, Inc. · JLW · May 1, 2015 · Clinical Chemistry

Device Facts

• Record ID: K150403
• Device Name: ADVIA Centaur TSH3-Ultra
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: JLW · Clinical Chemistry
• Decision Date: May 1, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1690
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

For in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in serum, heparinized plasma, and EDTA plasma using the ADVIA Centaur and ADVIA Centaur XP systems. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

Device Story

In vitro diagnostic assay for quantitative TSH measurement in serum, heparinized plasma, and EDTA plasma; performed on ADVIA Centaur XP systems. Device measures TSH levels to assist clinicians in diagnosing thyroid or pituitary disorders. Operation involves automated immunoassay processing; results provided to healthcare providers for clinical decision-making regarding thyroid function. Benefits include standardized reference intervals for pediatric populations (infants, children, adolescents) to improve diagnostic accuracy across age groups.

Clinical Evidence

No new clinical performance testing was conducted for this submission. The device relies on previously established analytical performance data from K083844. Pediatric reference intervals were established by analyzing data from 442 patients (94 infants, 198 children, 150 adolescents) to define normal ranges for these populations.

Technological Characteristics

In vitro diagnostic immunoassay; quantitative determination of TSH. Utilizes ADVIA Centaur XP system instrumentation. Analytical measuring range: 0.008 – 150 µIU/mL. No changes to materials, sensing principle, or manufacturing process compared to predicate. Software-controlled automated analysis.

Indications for Use

Indicated for quantitative determination of TSH in serum, heparinized plasma, and EDTA plasma for the diagnosis of thyroid or pituitary disorders in patients including infants (1-23 months), children (2-12 years), adolescents (13-21 years), and adults.

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)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k150403

B. Purpose for Submission:
Adding updated pediatric reference ranges and new infant reference ranges to a previously cleared assay, k083844.

C. Measurand:
Thyroid Stimulating Hormone (TSH)

D. Type of Test:
Quantitative, chemiluminescence immunoassay

E. Applicant:
Siemens Healthcare Diagnostics Inc.

F. Proprietary and Established Names:
ADVIA Centaur TSH3-Ultra

G. Regulatory Information:
1. Regulation section:
21 CFR § 862.1690, Thyroid stimulating hormone test system
2. Classification:
Class II
3. Product code:
JLW
4. Panel:
Clinical Chemistry (75)

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H. Intended Use:

1. Intended use(s):

See Indications(s) for use below

2. Indication(s) for use:

For in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in serum, heparinized plasma, and EDTA plasma using the ADVIA Centaur and ADVIA Centaur XP systems. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.

3. Special conditions for use statement(s):

For prescription use

4. Special instrument requirements:

ADVIA Centaur and ADVIA Centaur XP systems.

I. Device Description:

ADVIA Centaur TSH3-Ultra (TSH3-UL) kit consists of the following reagents:

Ultra-Lite Reagent- bovine serum albumin (BSA) conjugated to monoclonal anti- TSH (~0.3 µg/mL) labeled with acridinium ester in HEPES buffered saline, mouse IgG, BSA, goat serum, surfactant, and preservatives.

Solid Phase Reagent - anti-fluorescein monoclonal mouse antibody covalently linked to paramagnetic particles (PMP) (~85 µg/mL) in HEPES buffered saline, BSA, goat serum, surfactant, and preservative.

Ancillary Well Reagent - Fluorescein isothiocyanate conjugated to monoclonal anti-TSH (~3 µg/mL) in HEPES buffered saline, mouse IgG, BSA, goat serum, surfactant, and preservative.

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J. Substantial Equivalence Information:

1. Predicate device name(s):
ADVIA Centaur TSH3-Ultra

2. Predicate 510(k) number(s):
k083844

3. Comparison with predicate:

| Similarities and Differences | | |
| --- | --- | --- |
| Item | Candidate device ADVIA Centaur TSH3-Ultra | Predicate Device ADVIA Centaur TSH3-Ultra (k083844) |
| Intended Use | For in vitro diagnostic use in the quantitative determination of thyroid-stimulating hormone (TSH, thyrotropin) in serum, heparinized plasma, and EDTA plasma. | Same |
| Reagents | ADVIA Centaur TSH3-Ultra | Same |
| Analyzers | ADVIA Centaur, ADVIA Centaur XP | Same |
| Analytical Measuring Range (Assay Range) | 0.008 – 150 μIU/mL | Same |
| Infant Reference Intervals | 1 month -23 months: 0.87 - 6.15 μIU/mL | None |
| Children Reference Intervals | 2 to 12 years: 0.67 - 4.16 μIU/mL | 2 to less than 12 years: 0.636 -6.267 μIU/mL |

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| Adolescents Reference Intervals | 13 years – 20 years: 0.48 - 4.17 μIU/mL | 12 to less than 18 years: 0.51-4.94 μIU/mL |
| --- | --- | --- |
| Adult Reference Intervals | 21 years and older: 0.55– 4.78 μIU/mL | 18 years and older: 0.55– 4.78 μIU/mL |

K. Standard/Guidance Document Referenced (if applicable):

Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition (CLSI C28-A3).

L. Test Principle:

The ADVIA Centaur TSH3-Ultra assay is a third-generation assay that employs anti-FITC monoclonal antibody covalently bound to paramagnetic particles, and FITC-labeled anti-TSH capture monoclonal antibody, and a tracer consisting of a proprietary acridinium ester and an anti-TSH monoclonal antibody conjugated to bovine serum albumin (BSA) for chemiluminescent detection. A direct relationship exists between the amount of TSH present in the patient sample and the amount of relative light units (RLUs) detected by the system.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Provided in k083844.

b. Linearity/assay reportable range:

Provided in k083844.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Provided in k083844.

d. Detection limit:

Provided in k083844.

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e. Analytical specificity:
Provided in k083844.

f. Assay cut-off:
Not applicable

2. Comparison studies:
a. Method comparison with predicate device:
Provided in k083844.
b. Matrix comparison:
Provided in k083844.

3. Clinical studies:
a. Clinical Sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
A pediatric reference range study using population age from 1 month old to 20 years old was conducted. Serum samples were collected at 8 U.S. sites to be representative of the U.S. population diversity. Data from a total of 442 pediatric patients (94 infants, 198 children, and 150 adolescents) from one ADVIA Centaur analyzer and three reagent lots were analyzed to establish the ADVIA Centaur TSH-3 Ultra assay reference ranges for the studied pediatric population. Results from the $2.5^{\text{th}}$ to $97.5^{\text{th}}$ percentile were used as the pediatric reference ranges. The reference interval for the infant group was calculated

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by performing a log-transformation of the raw data followed by the application of the robust symmetric method to the transformed data. This approach was selected to be most appropriate for the smaller sample size as the data from this population was highly skewed to the right and a transformation was necessary to obtain a normal distribution. The sponsor has added language to their package insert explaining the uncertainty in the value for the upper limit of the reference range. A non- parametric approach was used to establish the reference intervals for children and adolescents based on the CLSI C28-A3 recommendation because the sample size was greater than 120. Reference ranges are summarized in the table below.

| Age Range | Reference Ranges |
| --- | --- |
| Infants (01 – 23 months) | 0.87 - 6.15 μIU/mL |
| Children (02 – 12 years) | 0.67 - 4.16 μIU/mL |
| Adolescents (13 – 20 years) | 0.48- 4.17 μIU/mL |

Confidence intervals for the limits of the infant reference range are as follows:

| | Lower Limit of reference range | Upper Limit of reference range |
| --- | --- | --- |
| 90% confidence intervals: | 0.74- 1.04 μIU/mL | 5.32 – 6.98 μIU/mL |

# N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

# O. Conclusion:

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