ADVIA Centaur Total IgE (tIgE)

K193493 · Siemens Healthcare Diagnostics, Inc. · DGC · Jan 15, 2020 · Immunology

Device Facts

• Record ID: K193493
• Device Name: ADVIA Centaur Total IgE (tIgE)
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: DGC · Immunology
• Decision Date: Jan 15, 2020
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5510
• Device Class: Class 2

Intended Use

For in vitro diagnostic use in the quantitative determination of total IgE in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur®, ADVIA Centaur XP, and ADVIA Centaur XPT systems.

Device Story

ADVIA Centaur Total IgE (tIgE) is a two-site sandwich immunoassay using direct chemiluminometric technology. It measures total IgE in serum and plasma (EDTA and lithium heparin) samples. The assay utilizes a goat anti-human IgE antibody labeled with acridinium ester (Lite Reagent) and a mouse anti-human IgE antibody coupled to paramagnetic particles (Solid Phase Reagent). The device is used in clinical laboratory settings on the ADVIA Centaur family of analyzers. Results are determined via a 2-point calibration curve and a master curve. Healthcare providers use the quantitative IgE results to assist in clinical decision-making related to immunological conditions. The device benefits patients by providing standardized IgE measurements for diagnostic assessment.

Clinical Evidence

No clinical data. Evidence consists of analytical performance testing, including interference studies (spiking K2-EDTA and lithium heparin at 3x and 5x concentrations) and matrix comparison studies. Matrix comparison used 73 paired serum/K2-EDTA samples and 73 paired serum/Li-heparin samples, demonstrating equivalence with slopes of 0.99 and 1.00 respectively and correlation coefficients of 1.00.

Technological Characteristics

Two-site sandwich immunoassay; direct chemiluminometric technology. Capture antibody: mouse anti-human IgE on paramagnetic particles. Detection antibody: goat anti-human IgE labeled with acridinium ester. Sample volume: 30 µL. Calibration: 2-point. Traceability: WHO 75/502. Analyzers: ADVIA Centaur, XP, XPT. Standards: CLSI EP07-ed3, CLSI EP17-A2, CLSI EP09-A3.

Indications for Use

Indicated for the quantitative determination of total IgE in serum and plasma (EDTA and lithium heparin) for in vitro diagnostic use on ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT systems.

Regulatory Classification

Identification

An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.

Predicate Devices

• Acs Total Ige Immunoassay (K920372)

Submission Summary (Full Text)

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January 15, 2020

Siemens Healthcare Diagnostics Inc. Ian Thompson Regulatory Clinical Affairs Specialist 511 Benedict Avenue Tarrytown, New York 10591

Re: K193493

Trade/Device Name: ADVIA Centaur Total IgE (tIgE) Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A, G, M, D, and E immunological test system Regulatory Class: Class II Product Code: DGC Dated: December 16, 2019 Received: December 17, 2019

Dear Ian Thompson:

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 (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 located 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.

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

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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 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,

Carolina Kagan Acting Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) K193493

Device Name ADVIA Centaur® Total IgE (tIgE)

Indications for Use (Describe)

For in vitro diagnostic use in the quantitative determination of total IgE in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur®, ADVIA Centaur XP, and ADVIA Centaur XPT systems.

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of 21 CFR 807.92 and the Safe Medical Device Act of 1990.

The assigned 510(k) Number is: K193493

## 1. Date Prepared

December 13, 2019

### 2. Applicant Information

| Contact: | Ian Thompson<br>Regulatory Clinical Affairs Specialist |
|----------|-----------------------------------------------------------------------------------|
| Address: | Siemens Healthcare Diagnostics Inc.<br>511 Benedict Avenue<br>Tarrytown, NY 10591 |
| Phone: | 914-524-2296 |
| Fax: | 914-524-2101 |
| Email: | [e-mail] |

#### Regulatory Information 3.

# Table 1. Regulatory Information for ADVIA Centaur® Total IgE (tlgE)

| Trade Name | ADVIA Centaur Total IgE (tIgE) |
|------------------------|-------------------------------------------------------------|
| Device | IgE, Antigen, Antiserum, Control |
| Regulation Description | Immunoglobulins A, G, M, D, and E immunological test system |
| FDA Classification | Class II |
| Review Panel | Immunology |
| Product Code | DGC |
| Regulation Number | 21 CFR 866.5510 |

#### 4. Predicate Device Information

Predicate Device Name: ADVIA Centaur® Total IgE (tIgE)

510(k) Number: K920372

The ADVIA Centaur Total IgE (tlgE) assay with the addition of the plasma (EDTA and lithium heparin) sample and new detection capability [Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ)] claims in the Instructions for Use (Package Inserts) are substantially equivalent to the ADVIA Centaur Total IgE (tlgE) assay that was cleared under 510(k) K920372, as shown below in the Substantial Equivalence Information section.

## 5. Intended Use

For in vitro diagnostic use in the quantitative determination of total IgE in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur®, ADVIA Centaur XP, and ADVIA Centaur XPT systems.

## 6. Indications for Use

Same as Intended use.

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# Special Conditions for Use Statement(s): For prescription use only

### Device Description 7.

The ADVIA Centaur Total IgE (tlgE) assay is a two-site sandwich immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies to IqE. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve with the reagent bar code. The ADVIA Centaur Total IgE (tlgE) assay is intended for use on the ADVIA Centaur family of analyzers. The ADVIA Centaur Calibrator 80 is a set of 2 level calibrators for the assay. Siemens Healthcare Diagnostics recommends the use of commercially available quality control materials with at least 2 levels (low and high).

The ADVIA Centaur Total IgE (tlgE) reagent kit contains the following:

- ADVIA Centaur Total IgE ReadyPack primary reagent pack contains Lite Reagent and Solid . Phase Reagent.
Materials Required but Not provided:

- ADVIA Centaur Calibrator 80: consists of 2 levels (low and high) of human IgE calibrators in ● equine serum and preservatives; lyophilized.
Optional Reagents:

- ADVIA Centaur IgE Diluent: consists of IgE-free human plasma with sodium azide (0.1%).
- ADVIA Centaur IgE Master Curve Material: consists of MCM 1 that is Iyophilized human plasma ● with sodium azide (0.1% after reconstitution) and preservatives and MCM 2-7 that are various levels of IgE in Iyophilized human plasma with sodium azide (0.1% after reconstitution) and preservatives.

## 8. Purpose of the Submission

The purpose of this submission is for the addition of the plasma (EDTA and lithium heparin) sample claim and updating the detection capability claim for the ADVIA Centaur Total IgE (tlgE) assay.

# Substantial Equivalence Information - Comparison of Candidate 9. Device and Predicate Device

The following table demonstrates substantial equivalence between the ADVIA Centaur Total IgE (tlgE) assay (Candidate Device) that has modified Instructions for Use (Package Inserts) with the addition of plasma (EDTA and lithium heparin) sample and new detection capability (LoB, LoD, and LoQ) claims and the currently marketed ADVIA Centaur Total IgE (tlgE) assay (Predicate Device) that was cleared under 510(k) K920372.

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| Trade Name | Candidate Device | Predicate Device |
|---------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | ADVIA Centaur Total IgE (tIgE)<br>(Modified Labeling) | ADVIA Centaur Total IgE (tIgE)<br>(Unmodified Labeling) |
| Intended Use /<br>Indications for Use | For in vitro diagnostic use in the<br>quantitative determination of total IgE in<br>serum and plasma (EDTA and lithium<br>heparin) using the ADVIA Centaur®, ADVIA<br>Centaur XP, and ADVIA Centaur<br>XPT systems. | For in vitro diagnostic use in the<br>quantitative determination of total IgE in<br>serum using the ADVIA Centaur®,<br>ADVIA Centaur XP, and ADVIA Centaur<br>XPT systems. |
| Measurement | Quantitative | Same |
| Detection<br>Capability | LoB: 1.5 IU/mL<br>LoD: 2.0 IU/mL<br>LoQ: 2.5 IU/mL | Analytical Sensitivity: 1.5 IU/mL<br>NA*<br>NA |
| Assay Range | Serum and plasma: 2.5-3000 IU/mL | Serum: 1.5-3000 IU/mL |
| Operating Principle | two-site sandwich immunoassay | Same |
| Technology | Direct chemiluminescent | Same |
| Sample Type | Serum, plasma (EDTA and lithium heparin) | Serum |
| Sample Volume | 30 µL (serum and plasma) | 30 µL (serum) |
| Traceability/<br>Standardization | World Health Organization (WHO)<br>75/502 | Same |
| Calibration | 2-point | Same |
| Calibrator/Levels | Calibrator 80/2 levels | Same |
| Controls/Levels | Commercial Controls/2 levels | Same |
| Master Curve<br>Materials | Seven levels (MCM1-7) | Same |
| Detection Antibody | Goat anti-human IgE antibody labeled with<br>acridinium ester | Same |
| Capture Antibody | Mouse anti-human IgE antibody covalently<br>coupled to paramagnetic particles | Same |

* NA = Not applicable.

# Standard/Guidance Document References 10.

The following recognized standards from Clinical Laboratory Standards Institute (CLSI) were used as a basis of the study procedures described in this submission:

- Interference Testing in Clinical Chemistry; Approved Guideline-Third Edition. (CLSI EP07-● ed3).
- Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved ● Guideline-Second Edition (CLSI EP17-A2).

## Test Principle 11.

The ADVIA Centaur Total IgE (tlgE) assay is a two-site sandwich immunoassay using direct chemiluminometric technology, which uses constant amounts of two antibodies to lgE. The first antibody, in the Lite Reagent, is a goat anti-human IqE antibody labeled with acridinium ester. The second antibody, in the Solid Phase, is a mouse anti-human IgE antibody, which is covalently coupled to paramagnetic particles.

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# 12. Performance Characteristics

The addition of the plasma (EDTA and lithium heparin) sample and detection capability (LoB, LoD, and LoQ) claims in the Instructions for Use (Package Inserts) for the ADVIA Centaur Total IgE (tlgE) assay was demonstrated by testing the performance characteristics with the following studies:

- . Specimen Equivalence by Method Comparison
- . Detection Capability (LoB, LoD, LoQ)
- . Interferences: EDTA and Heparin

The plasma (EDTA and lithium heparin) sample and detection capability (LoB, LoD, and LoQ) claims for the ADVIA Centaur Total IgE (tlgE) assay do not require the collection of additional analytical performance data. Therefore, all analytical performance data previously reviewed for the ADVIA Centaur Total IgE (tlqE) assay continues to apply to this assay, because the assay was not modified.

#### Detection Limit 12.1

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

| Limit of Blank (LoB) | 1.5 IU/mL |
|-----------------------------|-----------|
| Limit of Detection (LoD) | 2.0 IU/mL |
| Limit of Quantitation (LoQ) | 2.5 IU/mL |

The LoB corresponds to the highest measurement likely to be observed for a blank sample with a probability of 95%.

The LoD corresponds to the lowest concentration of total IgE that can be detected with a probability of 95%.

The LoQ corresponds to the lowest amount of total IgE in a sample at which the within laboratory CV is ≤ 20%.

#### 12.2 Specimen Equivalence by Method Comparison

Specimen equivalency was determined with the weighted Deming linear regression model in accordance with CLSI Document EP09-A3. The following results were obtained:

| Comparison | N* | Sample Interval | Slope<br>(95% CI) | Intercept<br>(95% CI) | Correlation<br>Coefficient (r) |
|--------------------------------------|----|----------------------|-------------------------|--------------------------------|--------------------------------|
| Dipotassium EDTA Plasma<br>vs. Serum | 73 | 2.80 – 2748.84 IU/mL | 0.99<br>(0.975 - 1.012) | 0.28 IU/mL<br>(0.086 - 0.475) | 1.00 |
| Lithium Heparin vs. Serum | 73 | 2.80 - 2748.84 IU/mL | 1.00<br>(0.989 - 1.020) | 0.18 IU/mL<br>(-0.102 - 0.458) | 1.00 |

* N = Number of samples tested.

The assay is designed to have a slope of 0.90–1.10 for alternate tube types versus serum.

#### 12.3 Interferences: EDTA and Heparin

Interference testing was performed in accordance with CLSI Document EP07-ed3. The following results were obtained:

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| Interferent | Interferent Concentration | Analyte Concentration (IU/mL) | Bias (%) |
|------------------|---------------------------|-------------------------------|----------|
| Dipotassium EDTA | 9.0 mg/mL | 121.51 | -1.7 |
| | | 1624.13 | 1.4 |
| Heparin | 75 U/mL | 167.48 | -1.7 |
| | | 1450.12 | -1.1 |

#### Clinical Studies 12.4

Not applicable.

#### 12.5 Clinical Cut-off

Not applicable.

#### 13. Conclusion

The ADVIA Centaur Total IgE (tlgE) assay with the addition of the plasma (EDTA and lithium heparin) sample and new detection capability (LoB, LoD, and LoQ) claims in the Instructions for Use (package insert) is substantially equivalent to the currently marketed ADVIA Centaur Total IgE (tlgE) assay (K920372).