ADVIA Centaur IgE Master Curve Material

K143680 · Siemens Healthcare Diagnostics, Inc. · JJX · Jan 27, 2015 · Clinical Chemistry

Device Facts

• Record ID: K143680
• Device Name: ADVIA Centaur IgE Master Curve Material
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: JJX · Clinical Chemistry
• Decision Date: Jan 27, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1660
• Device Class: Class 1

Intended Use

The ADVIA Centaur® IgE Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Total IgE assay.

Device Story

ADVIA Centaur IgE Master Curve Material (MCM) consists of seven levels of lyophilized human plasma spiked with IgE, sodium azide, and preservatives; used for bi-annual calibration verification and linearity checks of ADVIA Centaur Total IgE assays. Operated by laboratory technicians on ADVIA Centaur systems. Device provides target values (0.0 to 3150 IU/mL) for comparison against system-generated results. Discrepancies between observed and target values indicate need for recalibration or maintenance. Benefits include ensuring assay accuracy and compliance with accreditation requirements.

Clinical Evidence

Bench testing only. Stability studies (real-time shelf-life, open-vial, and on-board) confirmed performance within specifications. Value assignment was validated using reference calibrators traceable to WHO 75/502 standard.

Technological Characteristics

Lyophilized human plasma matrix with 0.1% sodium azide. Seven-level set (MCM1-7). Traceable to WHO 75/502 reference material. Designed for use on ADVIA Centaur systems. Stability: 8 months unopened at 2-8°C; 28 days reconstituted at 2-8°C; 4 hours on-board.

Indications for Use

Indicated for use as a quality control material to verify calibration and reportable range of the ADVIA Centaur Total IgE assay in a clinical laboratory setting.

Regulatory Classification

Identification

A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

January 27, 2015

Siemens Healthcare Diagnostics, Inc. c/o Ms. Fatima Pacheco Regulatory Clinical Affairs Specialist 511 Benedict Avenue Tarrytown, NY 10591

Re: k143680

Trade/Device Name: ADVIA Centaur® IgE Master Curve Material Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: Class I, Reserved Product Code: JJX Dated: December 19, 2014 Received: January 5, 2015

Dear Ms. Pacheco:

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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

## Leonthena R. Carrington -A

Leonthena Carrington, MS, MBA, MT (ASCP) Director (Acting) Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known) k143680

Device Name

ADVIA Centaur® IgE Master Curve Material

Indications for Use (Describe)

The ADVIA Centaur® IgE Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Total IgE assay.

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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# SIEMENS

## 510(k) Summary

### 510(k) Summary – ADVIA Centaur IgE Master Curve Material

Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.

#### The assigned 510(k) Number: k143680

| 1. Applicant Information | Siemens Healthcare Diagnostics Inc. |
|--------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Mailing Address: | 511 Benedict Avenue<br>Tarrytown, NY 10591 USA |
| Contact Person: | Fatima Pacheco<br>Regulatory Clinical Affairs Specialist |
| Phone Number: | [phone] |
| Fax Number: | [phone] |
| E-mail Address: | [e-mail] |
| Date Prepared: | January 26, 2015 |
| 2. Device Name | |
| Proprietary Name: | ADVIA Centaur® IgE Master Curve Material |
| Measurand: | Quality Control materials for ADVIA Centaur IgE assay |
| Type of Test: | Master Curve Material (MCM) for ADVIA Centaur IgE assay<br>21 CFR 862.1660, Quality Control Material |
| Regulation Section: | Class I Reserved |
| Classification: | JJX - Single (Specified) Analyte Controls (Assayed and<br>Unassayed) |
| Products Code: | Unassayed) |
| Panel: | Immunology (82) |
| 3. Predicate Device Name | IMMULITE 2000 Total IgE Calibration Verification Material<br>(CVM) |
| Predicate 510(k) No: | k133122 |
| 4. Device Description: | ADVIA Centaur® IgE Master Curve Material is an <i>in vitro</i><br>diagnostic product containing various levels of IgE spiked in<br>lyophilized human plasma with sodium azide (0.1%) and<br>preservatives. Each set contains seven levels (MCM1–7); with a<br>reconstituted volume of 1.0 mL/vial per level. MCM1contains<br>no analyte. The MCMs assigned values are lot-specific of target |

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# SIEMENS

| | values: 0.0, 12.5, 40.0, 270, 1000, 1700, and 3150 IU/mL. |
|-----------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 5. Intended Use:<br>Indication for Use: | See Indications for Use Statement below:<br>The ADVIA Centaur® IgE Master Curve Material is for in vitro<br>diagnostic use in the verification of calibration and reportable<br>range of the ADVIA Centaur Total IgE assay. |
| Special Conditions for<br>Use Statement(s): | For prescription use only |
| Special Instrument<br>Requirements: | ADVIA Centaur® Systems<br>A description of the ADVIA Centaur system is documented<br>in k971418. Subsequent modifications to the instrument have<br>been reviewed and cleared in k032525 and k041133. |
| 6. Technological Characteristics<br>and Substantial Equivalence<br>Comparison with Predicate: | A comparison of the device features, intended use, and other<br>information demonstrates that the ADVIA Centaur IgE MCM is<br>substantially equivalent to the predicate device as summarized<br>in Table 1. |

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| SIMILARITIES | | |
|-----------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Candidate Device | Predicate Device |
| Item | ADVIA Centaur IgE MCM | IMMULITE 2000 Total IgE<br>Calibration Verification Material<br>(CVM) |
| Intended<br>Use | The ADVIA Centaur IgE Master Curve<br>Material is for <i>in vitro</i> diagnostic use in<br>the verification of calibration and<br>reportable range of the ADVIA<br>Centaur tIgE assay. | The IMMULITE 2000 Total IgE<br>Calibration Verification Material<br>(CVM) is intended for <i>in vitro</i><br>diagnostic use, as a control for<br>calibration verification of the<br>IMMULITE 2000 Total IgE assay on<br>IMMULITE 2000 systems as<br>indicated in the CVM Package Insert. |
| Analyte | IgE | Same |
| DIFFERENCES | | |
| Form | Lyophilized | Liquid |
| Storage | 2-8°C | ≤ -20°C |
| Use | Multiple Use | Single Use |
| Matrix | Human plasma | Equine serum |
| Levels | 7 | 4 |
| Stability | Unopened - Stable when stored<br>unopened at 2-8°C for 8 months.<br>Opened (Reconstituted) – Stable<br>when stored at 2-8°C for 28 days; or<br>on-board for 4 hours. | Unopened - Stable until the<br>expiration date on the vial. |

Table 1: Substantial Equivalence Comparison

#### 7. Standard/Guidance Document References

The following recognized standard and guidance documents were used:

- Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic ● Calibrators
- Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control ● Material

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### 8. Test Principle

The MCMs are specifically intended for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur assays for use on the ADVIA Centaur systems. Customers may use MCMs for bi-annual calibration verification checks of the assay range and linearity in order to meet the requirements of hospital accreditation bodies.

#### 9. Performance Characteristics

#### 9.1 Analytical performance:

The following studies are not applicable for the purpose of this submission:

- Precision/Reproducibility ●
- Linearity/Assay Reportable Range .
- Detection limit ●
- Analytical Specificity ●
- Assay cut-off ●
- Method Comparison Studies ●
- Clinical Studies (Sensitivity, Specificity, and cut-off) ●

#### 9.2 Non-Clinical Performance Testing

#### 9.2.1 Stability Studies

Stability studies were conducted on the ADVIA Centaur system to support the shelf life (unopened) and reconstituted material for the ADVIA Centaur IgE MCMs to ensure that it maintains optimal product performance throughout the established shelf-life. The data supports the stability claims detailed in the ADVIA Centaur IgE MCM Instructions for Use.

The following stability studies were performed for ADVIA Centaur IgE MCM:

- Real Time/Shelf Life (unopened) Stability
- In Use Open Vial (reconstituted) stored at 2-8°C Stability ●
- On-Board Stability

Real time shelf-life studies (unopened): Test IgE MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 7 months, 8 months, 9 months, 11 months,12 months, 18 months, 35 months and 36 months. Shelf life claims are based upon real time stability carried out one month after the duration claimed. Real time shelf-life stability studies of MCMs were determined by comparison of dose recoveries at T=0. Current testing meets the sponsor's acceptance criteria for the real-time stability study up to the 9 months' time point, which supports a shelf-life claim of 8 months. Storage shelf-life (unopened) at 2-8°C is indicated by the expiration date on the vial label.

In-Use Open Vial (Reconstituted): Test IgE MCMs were reconstituted, each level pooled, aliquotted and stored at 2-8°C, tested in 5 replicates per level at T=0, 7, 14, 21, 28, and 29 days on the ADVIA Centaur XP system. Acceptance criteria for the open vial (reconstituted) stability study were met to the 29 days' time point, which supports the open vial claim of 28 days when properly stored at 2-8°C.

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On-board Stability: Pooled aliquots of test IgE MCMs in sample cups were stored on the ADVIA Centaur XP system and measured at time point T=0, 2, 4 and 5 hours. On-board stability studies of MCMs were determined by comparison of dose recoveries to the T=0 dose recovery results. Acceptance criteria for the on-board stability study were met up to 5 hours, which supports the on-board stability claim for 4 hours.

#### Stability Acceptance Criteria

The stability specifications acceptance criteria for the ADVIA Centaur IgE MCM are as follows:

- Real Time/Shelf life (Unopened): The dose recovery for MCM1 must be . ≤ 2.0 IU/mL dose; MCM2-7, the % dose recovery met the sponsor's required acceptance criteria.
- In-Use Open Vial (Reconstituted): The dose recovery for MCM1 must be < 2.0 IU/mL dose: MCM2-7, the % dose recovery met the sponsor's required acceptance criteria.
- On-Board: The dose recovery for MCM1 must be ≤ 2.0 IU/mL dose; . MCM2-7, the % dose recovery met the sponsor's required acceptance criteria.

#### 9.2.2 Value Assignment

The ADVIA Centaur IgE MCMs are value assigned using assigned reference calibrators and MCMs. The assigned reference calibrators are prepared using IgE stock and are traceable to internal material which is standardized against World Health Organization (WHO) 75/502 reference material. The MCMs are manufactured using qualified materials and measurement procedures.

For each new IgE MCM lot manufactured, MCM1 is run in 5 replicates on two separate runs using one reagent kit lot on the ADVIA Centaur system. A nested testing run protocol is used for MCM2-MCM7 value assignment. This consists of running alternating samples of the reference and new MCM level in the same run. MCM2-MCM7 were tested on 20 replicates in total, comprised of one run and four sample cups run in 5 replicates on one system and one reagent kit lot. This protocol is designed to remove system and run variation. The new MCM doses must fall within the final value assignment specification for IgE MCMs. The MCMs dose values are generated using the two-point calibration. The new MCM dose is calculated based on the relationship between the observed reference MCM dose and its assigned value. A performance verification run consisting of 6 replicates of each MCM level is run using one instrument, one reagent kit lot and Bio-Rad controls. The mean MCM doses of the new MCM lot manufactured must fall within the customer range specifications.

The target for MCM1 is assigned a 0.0 dose. MCM1 is analyte-free basepool comprising of only the matrix and preservatives. The quality control specifications and final value assignment limits for IgE MCM ensure that MCM1 measures at or below the IgE assay sensitivity limit. MCM7 targeted greater than

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the assay range is diluted with the MCM1 to meet the reportable range of the assay.

#### 9.2.3 Expected Values

The expected values are the lot-specific assigned values obtained at value assignment and the lot-specific assigned ranges are the lot-specific customer ranges are established per the sponsor's internal procedural specifications for IgE MCM.

ADVIA Centaur IgE MCM levels and target values are provided in Table 2.

| MCM level | Target Values<br>(IU/mL) |
|-------------|--------------------------|
| MCM1 | 0.00 |
| MCM2 | 12.5 |
| MCM3 | 40.0 |
| MCM4 | 270 |
| MCM5 | 1000 |
| MCM6 | 1700 |
| MCM7 | 3150 |
| Assay Range | 1.5-3000 IU/mL |

Table 2: IgE MCM Levels and Target Values

#### 9.2.4 Traceability

The ADVIA Centaur tIgE assay is standardized against the World Health Organization (WHO) 75/502. Assigned values for calibrators and MCMs are traceable to this standardization. Assigned values for calibrators and MCMs are traceable to this standardization. The IgE MCMs are manufactured using qualified materials and measurement procedures.

#### 10. Proposed Labeling

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

#### 11. Conclusion

The ADVIA Centaur IgE Master Curve Material (MCM) is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed IMMULITE 2000 Total IgE CVM. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur IgE Master Curve Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.