The ADVIA Centaur® Follicle Stimulating Hormone (FSH) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur FSH assay.
The ADVIA Centaur® Free thyroxine (FT4) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur FT4 assay.
The ADVIA Centaur® Thyroxine (T4) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur T4 assay.
The ADVIA Centaur® Triiodothyronine (T3) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur T3 assay.

Device Description

ADVIA Centaur® FSH Master Curve Material is an in vitro diagnostic product containing various levels of follicle stimulating hormone spiked in lyophilized equine serum with sodium azide (0.1% after reconstitution) and preservatives. Each set contains eight levels (MCM1–8); with a reconstituted volume of 1.0 mL/vial per level. MCM1contains no analyte. The MCMs assigned values are lot-specific of target values: 0.00, 1.50, 4.50, 12.0, 30.0, 62.5, 130, 225 mIU/mL.
ADVIA Centaur® FT4 Master Curve Material is an in vitro diagnostic product containing various levels of thyroxine in human plasma with sodium azide. Each set contains seven levels; with a reconstituted volume of 1.0 mL/vial per level. MCM1 contains no analyte. The FT4 MCMs assigned values are lot-specific of target values: 0.00, 2.00, 5.00, 10.0, 15.0, 22.0, and 35.0 µg/dL which corresponds to FT4 values of 0.00, 0.42, 0.80, 1.70, 3.0, 5.6, and 13.5 ng/dL.
ADVIA Centaur® T4 Master Curve Material is an in vitro diagnostic product containing various levels of levothyroxine in human plasma with sodium azide and preservatives. Each set contains six levels; with a reconstituted volume of 1.0 mL/vial per level. MCM1 contains no analyte. The T4 MCMs assigned values are lot-specific of target values: 0.00, 2.50, 5.00, 10.0, 15.0. and 35.0 µg/dL.
ADVIA Centaur® T3 Master Curve Material is an in vitro diagnostic product containing various levels of liothyronine in human plasma with sodium azide and preservatives. Each se contains seven levels; with a reconstituted volume of 1.0 mL/vial per level. MCM1 contains no analyte. The T3 MCMs assigned values are lot-specific of target values: 0.00, 0.42, 0.69, 1.11, 1.65, 3.87, and 7.00 ng/mL.

AI/ML Overview

The provided document describes the Siemens Healthcare Diagnostics ADVIA Centaur® Master Curve Materials (MCM) for Follicle Stimulating Hormone (FSH), Free Thyroxine (FT4), Thyroxine (T4), and Triiodothyronine (T3). These devices are quality control materials used for verification of calibration and reportable ranges of their respective ADVIA Centaur assays. The information is presented as a 510(k) Summary, which focuses on demonstrating substantial equivalence to predicate devices, rather than a detailed report of a clinical study for device performance against specific patient outcomes or diagnostic accuracy.

Here's a breakdown of the requested information based on the provided text, with an emphasis on its applicability to in vitro diagnostic quality control materials rather than typical diagnostic imaging AI studies, which often involve human readers and expert consensus.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for these devices are primarily related to stability (shelf-life, open vial, and on-board stability) and value assignment. The reported performance indicates that these criteria were met.

ADVIA Centaur® FSH Master Curve Material

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Stability
Real Time/Shelf Life (Unopened)	The dose recovery for MCM1 (analyte-free) and the % dose recoveries for MCM2-8 met the sponsor's required acceptance criteria.	Current testing meets acceptance criteria up to the 7 months' time point, supporting a 6-month shelf-life claim (storage unopened at 2-8°C). Real-time studies are ongoing.
In-Use Open Vial (Reconstituted)	The dose recovery for MCM1 (analyte-free) and the % dose recoveries for MCM2-8 met the sponsor's required acceptance criteria.	Acceptance criteria for open vial (reconstituted) stability study were met up to the 29 days' time point, supporting an open vial claim of 28 days (when properly stored at 2-8°C).
On-Board Stability	The dose recovery for MCM1 (analyte-free) and the % dose recoveries for MCM2-8 met the sponsor's required acceptance criteria.	On-board stability study met acceptance criteria at the 5 hours' time point, supporting an on-board stability claim for 4 hours.
Value Assignment	The new MCM doses must fall within the final value assignment specification for FSH MCMs. The mean MCM doses of the new MCM lot manufactured must fall within the customer range specifications. MCM1 must measure at or below the FSH assay sensitivity limit.	The document states MCMs are value assigned using assigned reference calibrators and MCMs, and that MCMs are manufactured using qualified materials and measurement procedures. Performance verification runs (6 replicates per level) are conducted to ensure mean MCM doses fall within customer range specifications. No specific values or a pass/fail statement for a particular lot is provided, but implies acceptance criteria were met as part of the overall substantial equivalence.
Expected Values	Lot-specific assigned values and customer ranges are established per sponsor's internal procedural specifications.	Example target values (mIU/mL): MCM1: 0.00, MCM2: 1.50, MCM3: 4.50, MCM4: 12.0, MCM5: 30.0, MCM6: 62.5, MCM7: 130, MCM8: 225. Assay Range: 0.3–200 mIU/mL.
Traceability	Standardized against WHO 2nd International Standard for human FSH (IS 94/632).	ADVIA Centaur FSH = 0.91 (WHO) - 0.18 mIU/mL (r = 0.999). Assigned values for calibrators/MCMs are traceable to this standardization.

ADVIA Centaur® FT4 Master Curve Material

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Stability
Real Time/Shelf Life (Unopened)	The dose recovery for MCM1 and the % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.	Acceptance criteria met up to the 7 months' time point, supporting a 6-month shelf-life claim (storage unopened at 2-8°C). Real-time studies are ongoing.
In-Use Open Vial (Reconstituted)	The dose recovery for MCM1 and the % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.	Acceptance criteria met, supporting an open vial claim of 14 days (when properly stored at 2–8°C).
On-Board Stability	The dose recovery for MCM1 and the % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.	Acceptance criteria met up to 5 hours, supporting an on-board stability claim for 4 hours.
Value Assignment	The new MCM doses must fall within the final value assignment specification for FT4 MCMs. The mean MCM doses must fall within customer range specifications. MCM1 must measure at or below the FT4 assay sensitivity limit.	MCMs are value assigned using assigned reference calibrators and MCMs. Performance verification run (6 replicates per level) ensures mean MCM doses fall within customer range specifications. A nested testing run protocol is used for MCM2-7 value assignment (20 replicates in total). Implies acceptance criteria were met.
Expected Values	Lot-specific assigned values and customer ranges are established per sponsor's internal procedural specifications.	Example target values (ng/dL): MCM1: 0.00, MCM2: 0.42, MCM3: 0.80, MCM4: 1.70, MCM5: 3.0, MCM6: 5.6, MCM7: 13.5. Assay Range: 0.1-12.0 ng/dL.
Traceability	Standardized to an internal standard manufactured using USP (United States Pharmacopeia) material.	Assigned values for calibrators and MCMs are traceable to this standardization.

ADVIA Centaur® T4 Master Curve Material

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Stability
Real Time/Shelf Life (Unopened)	The dose recovery for MCM1 and the % dose recoveries for MCM2-6 met the sponsor's required acceptance criteria.	Acceptance criteria met up to the 11 months' time point, supporting a 10-month shelf-life claim (storage unopened at 2-8°C). Real-time studies are ongoing. (No information on open vial or on-board stability for T4 MCM in this summary)
Value Assignment	The new MCM doses must fall within the final value assignment specification for T4 MCMs. The mean MCM doses must fall within customer range specifications. MCM1 must measure at or below the T4 assay sensitivity limit.	MCMs are value assigned using assigned reference calibrators and MCMs. Performance verification run (6 replicates per level) ensures mean MCM doses fall within customer range specifications. A nested testing run protocol is used for MCM2-6 value assignment (20 replicates in total). MCM6 is diluted 1:4 before testing to meet reportable range. Implies acceptance criteria were met.
Expected Values	Lot-specific assigned values and customer ranges are established per sponsor's internal procedural specifications.	Example target values (µg/dL): MCM1: 0.00, MCM2: 2.50, MCM3: 5.00, MCM4: 10.0, MCM5: 15.0, MCM6: 35.0. Assay Range: 0.3–30.0 µg/dL.
Traceability	Standardized to an internal standard manufactured using USP (United States Pharmacopeia) material.	Assigned values for calibrators and MCMs are traceable to this standardization.

ADVIA Centaur® T3 Master Curve Material

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Stability
Real Time/Shelf Life (Unopened)	The dose recovery for MCM1 and the % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.	Acceptance criteria met up to the 11 months' time point, supporting a 10-month shelf-life claim (storage unopened at 2-8°C). Real-time studies are ongoing.
In-Use Open Vial (Reconstituted)	The dose recovery for MCM1 and the % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.	Acceptance criteria met up to the 22 days' time point, supporting an open vial claim of 21 days (when properly stored at 2-8°C).
On-Board Stability	The dose recovery for MCM1 and the % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.	Acceptance criteria met up to 5 hours, supporting an on-board stability claim for 4 hours.
Value Assignment	The new MCM doses must fall within the final value assignment specification for T3 MCMs. The mean MCM doses must fall within customer range specifications. MCM1 must measure at or below the T3 assay sensitivity limit.	MCMs are value assigned using assigned reference calibrators and MCMs. Performance verification run (6 replicates per level) ensures mean MCM doses fall within customer range specifications. A nested testing run protocol is used for MCM2-7 value assignment (20 replicates in total). Implies acceptance criteria were met.
Expected Values	Lot-specific assigned values and customer ranges are established per sponsor's internal procedural specifications.	Example target values (ng/mL): MCM1: 0.00, MCM2: 0.42, MCM3: 0.69, MCM4: 1.11, MCM5: 1.65, MCM6: 3.87, MCM7: 7.00. Assay Range: 0.1-8 ng/mL.
Traceability	Standardized to an internal standard manufactured using USP (United States Pharmacopeia) material.	Assigned values for calibrators and MCMs are traceable to this standardization.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document describes several non-clinical performance tests, primarily stability studies and value assignment. These are prospective tests conducted by the sponsor (Siemens Healthcare Diagnostics Inc.).

Stability Studies (Test Set):
- Real Time/Shelf Life (Unopened): Each MCM (FSH, FT4, T4, T3) was stored unopened at 2-8°C and tested at T=0, 7 months, and 10 or 11 months. Ongoing studies were mentioned at further time points (e.g., 14, 18, 24, 25 months for FSH; 15, 19, 24, 30, 31 months for FT4, T4, T3). The comparison was made against -80°C reference MCMs. No specific number of replicate MCM vials tested at each time point is explicitly stated, other than 'test FSH MCMs were stored'.
- In-Use Open Vial (Reconstituted): Each MCM (FSH, FT4, T3) was reconstituted, pooled, aliquoted, and stored at 2-8°C. They were tested in 5 replicates per level at T=0, 7, 14, 21, 28, and 29 days (for FSH, T3) or T=0, 7, 14, 21, 28, and 29 days (for FT4). T4 MCM summary did not include open vial stability data details.
- On-Board Stability: Pooled aliquots of each MCM (FSH, FT4, T3) in sample cups were stored on the ADVIA Centaur system and measured at T=0, 2, 4, and 5 hours. T4 MCM summary did not include on-board stability data details.
Value Assignment (Test Set):
- For each new MCM lot, MCM1 (analyte-free) was run in 5 replicates on two separate runs.
- Other MCM levels (MCM2-8 for FSH, MCM2-7 for FT4/T3, MCM2-6 for T4) were tested using a nested testing run protocol with alternating samples of reference and new MCM, totaling 20 replicates.
- A performance verification run consisted of 6 replicates of each MCM level.
Data Provenance: The studies were conducted by Siemens Healthcare Diagnostics Inc., likely in the USA. The data is prospective, generated specifically for this 510(k) submission.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This type of in vitro diagnostic quality control material does not rely on "expert" interpretation in the same way as, for example, an imaging device. The "ground truth" for these materials is established through a process of:

Traceability: Standardization to internationally recognized reference materials (e.g., WHO 2nd International Standard for human FSH) or internal standards traceable to official pharmacopeia (USP T4, T3 stock).
Assigned Values: The values of the MCMs are assigned by the manufacturer based on these traceable standards and validated measurement procedures.
Internal Protocols: The "sponsor's internal procedural specifications" and "qualified materials and measurement procedures" form the basis for establishing the expected values and ranges.

Therefore, there are no "experts" (like radiologists) establishing ground truth in terms of diagnostic interpretation from patient data. The ground truth is analytical and based on metrological traceability and rigorous laboratory procedures.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Adjudication methods like 2+1 or 3+1 (where multiple experts independently assess and then resolve discrepancies) are not applicable here. These methods are used in scenarios involving subjective expert interpretation, often for imaging or clinical diagnosis. For these quality control materials, "ground truth" and performance are determined through quantitative analytical measurements against established reference values and statistical methods to ensure measurements fall within specified limits.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

MRMC studies are typically performed for diagnostic imaging devices where human readers (e.g., radiologists) interpret cases, sometimes with AI assistance. This document describes in vitro diagnostic quality control materials, not a diagnostic AI device that involves human interpretation of cases. Therefore, no MRMC comparative effectiveness study was performed, and thus no effect size for human reader improvement with AI assistance is mentioned.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies described are standalone in the sense that they evaluate the performance of the quality control materials themselves (stability, value assignment) within the ADVIA Centaur assay system, without direct human cognitive input being part of the 'device's' analytical function during testing. The "algorithm" here is the underlying immunoassay technology, and the MCM's performance is tested analytically.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth used for these quality control materials is analytical traceability to recognized international standards (WHO) or national pharmacopeia (USP) for the respective analytes. It also includes reliance on the sponsor's "qualified materials and measurement procedures" and internal procedural specifications for value assignment. This is an objective, quantitative ground truth, not derived from expert consensus, pathology, or outcomes data.

8. The sample size for the training set

The concept of a "training set" is relevant for machine learning algorithms. These devices are chemical/biological reagents designed as quality control materials for immunoassays, not AI algorithms. Therefore, there is no "training set" as understood in machine learning. The manufacturing processes and associated testing are quality control steps, not a machine learning training phase.

9. How the ground truth for the training set was established

As there is no "training set" in the machine learning sense for these devices, this question is not applicable. The establishment of ground truth for the performance evaluation (test set, as discussed in point 7) is through analytical traceability to standards.

Summary

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

July 17, 2015

SIEMENS HEALTHCARE DIAGNOSTICS, INC. FATIMA PACHECO REGULATORY CLINICAL AFFAIRS SPECIALIST 511 BENEDICT AVENUE TARRYTOWN NY 10591

Re: K143687

Trade/Device Name: ADVIA Centaur® Follicle Stimulating Hormone (FSH) Master Curve Material. ADVIA Centaur® FT4 Master Curve Material, ADVIA Centaur® T4 Master Curve Material, ADVIA Centaur® T3 Master Curve Material Regulation Number: 21 CFR 862.1660 Regulation Name: Ouality control material (assayed and unassayed) Regulatory Class: I, Reserved Product Code: JJX Dated: June 01, 2015 Received: June 02, 2015

Dear Fatima 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements

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as set forth in the quality systems (OS) 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 regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

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

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 (800) 638-2041 or (301) 796-7100 or at its Internet address

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

Sincerely yours,

Courtney Lias -S

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known) K143687

Device Name

ADVIA Centaur® Follicle Stimulating Hormone (FSH) Master Curve Material

Indications for Use (Describe)

The ADVIA Centaur® Follicle Stimulating Hormone (FSH) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur FSH 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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW!

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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510(k) Number (if known) K143687

Device Name

ADVIA Centaur® FT4 Master Curve Material

Indications for Use (Describe)

The ADVIA Centaur® Free thyroxine (FT4) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur FT4 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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW!

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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510(k) Number (if known) K143687

Device Name ADVIA Centaur® T4 Master Curve Material

Indications for Use (Describe)

The ADVIA Centaur® Thyroxine (T4) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur T4 assay.

Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW!

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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510(k) Number (if known) K143687

Device Name

ADVIA Centaur® T3 Master Curve Material

Indications for Use (Describe)

The ADVIA Centaur® Triiodothyronine (T3) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur T3 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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW!

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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Section 006: 510(k) Summary

510(k) Summary - ADVIA Centaur FSH 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: K143687

1. Applicant InformationMailing Address:	Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591 USA
Contact Person:	Fatima PachecoRegulatory Clinical Affairs Specialist
Phone Number:	(914) 524-2450
Fax Number:	(914) 524-3579
E-mail Address:	fatima.pacheco@siemens.com
Date Prepared:	July 13, 2015
2. Device Name
Proprietary Name:	ADVIA Centaur® Follicle Stimulating Hormone (FSH)Master Curve Material
Measurand:	Master Curve Material
Type of Test:	Quality Control materials for ADVIA Centaur FSH assayMaster Curve Material (MCM) for ADVIA Centaur FSH assay
Regulation Section:	21 CFR 862.1660, Quality Control Material
Classification:	Class I Reserved
Products Code:	JJX-Single (Specified) Analyte Controls (Assayed andUnassayed)
Panel:	Clinical Chemistry (75)
3. Predicate Device Name	IMMULITE 2000 FSH Calibration Verification Material(CVM)
Predicate 510(k) No:	K133124
4. Device Description:	ADVIA Centaur® FSH Master Curve Material is anin vitro diagnostic product containing various levels of folliclestimulating hormone spiked in lyophilized equine serum withsodium azide (0.1% after reconstitution) and preservatives.Each set contains eight levels (MCM1–8); with a reconstituted

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(Bundled) Abbreviated 510(k) Premarket Notification
ADVIA Centaur® FSH, FT4, T4, and T3 Master Curve Material (MCM)
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volume of 1.0 mL/vial per level. MCM1contains no analyte. The MCMs assigned values are lot-specific of target values: 0.00, 1.50, 4.50, 12.0, 30.0, 62.5, 130, 225 mIU/mL.

1. Intended Use: See Indications for Use Statement below: The ADVIA Centaur® Follicle Stimulating Hormone (FSH) Indication for Use: Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur FSH assay. Special Conditions for For prescription use only Use Statement(s):
- ADVIA Centaur® Systems Special Instrument Requirements: A description of the ADVIA Centaur system is documented in K971418. Subsequent modifications to the instrument have been reviewed and cleared in K032525 and K041133.
A comparison of the device features, intended use, and other 6. Technological Characteristics information demonstrates that the ADVIA Centaur FSH MCM and Substantial Equivalence Comparison with Predicate: is substantially equivalent to the predicate device as summarized in Table 1.

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SIMILARITIES
	Candidate Device	Predicate Device
Item	ADVIA Centaur FSH MCM	IMMULITE 2000 FSH CalibrationVerification Material (CVM)
IntendedUse	The ADVIA Centaur FollicleStimulating Hormone (FSH) MasterCurve Material is for in vitrodiagnostic use in the verification ofcalibration and reportable range of theADVIA Centaur FSH assay.	The IMMULITE FSH CalibrationVerification Material (CVM) is forin vitro diagnostic use in theverification of calibration of theIMMULITE FSH assay on theIMMULITE 2000systems.
Analyte	Follicle stimulating Hormone	Same
Matrix	Equine serum	Bovine serum
DIFFERENCES
Use	Multiple Use	Single Use
Form	Lyophilized	Liquid
Storage	2–8°C	≤ -20°C
Levels	8	4
Stability	Unopened – Stable when storedunopened at 2-8°C for 6 months.Opened (Reconstituted) – Stablewhen stored at 2–8°C for 28 days; oron-board for 4 hours.	Unopened - Stable at ≤ -20°C up tothe expiration date.

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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SIEMENS

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

Stability Studies 9.2.1

Stability studies were conducted on the ADVIA Centaur XP system to support the shelf life (unopened) and reconstituted material for the ADVIA Centaur FSH 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 FSH MCM Instructions for Use.

The following stability studies were performed for ADVIA Centaur FSH 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 FSH MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 7 months and 10 months. Real time studies are on-going at T=14 months, 18 months, 24 months, and 25 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 to -80°C reference MCMs. Current testing meets the sponsor's acceptance criteria for the real-time stability study up to the 7 months' time point, which supports a shelf-life claim of 6 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 FSH 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. The sponsor's 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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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® FSH, FT4, T4, and T3 Master Curve Material (MCM)

On-board Stability: Pooled aliquots of test FSH MCMs in sample cups were stored on the ADVIA Centaur 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. The on-board stability study met the sponsor's acceptance criteria at the 5 hours' time point, which supports the onboard stability claim for 4 hours.

Stability Acceptance Criteria

The sponsor's stability specifications acceptance criteria for the ADVIA Centaur FSH MCM are as follows:

Real Time/Shelf life (Unopened): The dose recovery for MCM1 and the ● % dose recoveries for MCM2-8 met the sponsor's required acceptance criteria.
. In-Use Open Vial (Reconstituted): The dose recovery for MCM1 and the % dose recoveries for MCM2-8 met the sponsor's required acceptance criteria.
On-Board: The dose recovery for MCM1 and the % dose recoveries for . MCM2-8 met the sponsor's required acceptance criteria.

9.2.2 Value Assignment

The ADVIA Centaur FSH MCMs are value assigned using assigned reference calibrators and MCMs. The assigned reference calibrators are prepared using follicle-stimulating hormone stock and are traceable to internal material which is standardized against World Health Organization (WHO) 2nd International Standard for human FSH (IS 94/632) reference material. The MCMs are manufactured using qualified materials and measurement procedures.

The new MCM doses must fall within the final value assignment specification for FSH 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 FSH MCM ensure that MCM1 measures at or below the FSH assay sensitivity limit. MCM8 targeted greater than the assay range is diluted with the MCM1 to meet the reportable range of the assay.

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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 established per the sponsor's internal procedural specifications for FSH MCM.

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

MCM level	Target Values(mIU/mL)
MCM1	0.00
MCM2	1.50
MCM3	4.50
MCM4	12.0
MCM5	30.0
MCM6	62.5
MCM7	130
MCM8	225
Assay Range	0.3—200 mIU/mL

Table 2: Example FSH MCM Levels and Target Values

Traceability 9.2.4

The ADVIA Centaur FSH assay is standardized against World Health Organization (WHO) 2nd International Standard for human FSH (IS 94/632) reference material based on the following correlation: ADVIA Centaur FSH = 0.91 (WHO) - 0.18 mIU/mL

r = 0.999

Assigned values for calibrators and MCMs are traceable to this standardization.

10. Proposed Labeling

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

11. Conclusion

The ADVIA Centaur FSH 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 FSH Calibration Verification Material (CVM). Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur FSH Master Curve Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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SIEMENS

(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® FSH, FT4, T4, and T3 Master Curve Material (MCM)

510(k) Summary – ADVIA Centaur FT4 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: K143687

1. Applicant InformationMailing Address:	Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591 USA
Contact Person:	Fatima PachecoRegulatory Clinical Affairs Specialist
Phone Number:	(914) 524-2450
Fax Number:	(914) 524-3579
E-mail Address:	fatima.pacheco@siemens.com
Date Prepared:	July 13, 2015
2. Device Name
Proprietary Name:	ADVIA Centaur® FT4 Master Curve Material
Measurand:	Quality Control materials for ADVIA Centaur FT4 assay
Type of Test:	Master Curve Material (MCM) for ADVIA Centaur FT4 assay
Regulation Section:	21 CFR 862.1660, Quality Control Material
Classification:	Class I Reserved
Products Code:	JJX - Single (Specified) Analyte Controls (Assayed and
	Unassayed)
Panel:	Clinical Chemistry (75)
3. Predicate Device NamePredicate 510(k) No:	IMMULITE 2000 FT4 Calibration Verification Material (CVM)K140818
4. Device Description:	ADVIA Centaur® FT4 Master Curve Material is an in vitrodiagnostic product containing various levels of thyroxine inhuman plasma with sodium azide. Each set contains sevenlevels; with a reconstituted volume of 1.0 mL/vial per level.MCM1 contains no analyte. The FT4 MCMs assigned valuesare lot-specific of target values: 0.00, 2.00, 5.00, 10.0, 15.0,22.0, and 35.0 µg/dL which corresponds to FT4 values of 0.00,0.42, 0.80, 1.70, 3.0, 5.6, and 13.5 ng/dL.
5. Intended Use:
Indication for Use:	See Indications for Use Statement below:The ADVIA Centaur® Free thyroxine (FT4) Master CurveMaterial is for in vitro diagnostic use in the verification ofcalibration and reportable range of the ADVIA Centaur FT4assay.
Special Conditions forUse Statement(s):	For prescription use only
Special InstrumentRequirements:	ADVIA Centaur® SystemsA description of the ADVIA Centaur system is documented inK971418. Subsequent modifications to the instrument have beenreviewed and cleared in K032525 and K041133.
6. Technological Characteristicsand Substantial EquivalenceComparison with Predicate:	A comparison of the device features, intended use, and otherinformation demonstrates that the ADVIA Centaur FT4 MCMis substantially equivalent to the predicate device assummarized in Table 1

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SIMILARITIES
	Candidate Device	Predicate Device
Item	ADVIA Centaur FT4 MCM	IMMULITE 2000 FT4 CalibrationVerification Material (CVM)
IntendedUse	The ADVIA Centaur Free thyroxine(FT4) MCM is for in vitro diagnosticuse in the verification of calibrationand reportable range of the ADVIACentaur FT4 assay.	The IMMULITE Free T4 CalibrationVerification Material (CVM) is forin vitro diagnostic use in the verificationof calibration of the IMMULITE Free T4assay on the IMMULITE 2000 systems.
Analyte	Free thyroxine	Same
Form	Lyophilized	Same
Matrix	Human plasma	Human serum
DIFFERENCES
Use	Multiple Use	Single Use
Storage	2–8°C	$\leq$ -20°C
Levels	7	4
Stability	Unopened – Stable when storedunopened at 2-8°C for 6 months.Opened (Reconstituted) – Stablewhen stored at 2–8°C for 14 days; oron-board for 4 hours.	Unopened - Stored at $\leq$ -20°C until theexpiration date.Opened (Reconstituted) – Stable for 8hours at 15-25°C.

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

8. Test Principle

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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 XP system to support the shelf life unopened and reconstituted material for the ADVIA Centaur FT4 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 FT4 MCM Instructions for Use.

The following stability studies were performed for ADVIA Centaur FT4 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 FT4 MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 7 months and 11 months. Real time studies are on-going at T=15 months, 19 months, 24months, 30 months, and 31 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 to the -80°C stored reference MCM. The sponsor's acceptance criteria for the real-time stability study were met up to the 7 months' time point, which supports a shelflife claim of 6 months. Unopened storage shelf-life is indicated by the expiration date on the vial label.

In-Use Open Vial (Reconstituted): Test FT4 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. The sponsor's acceptance criteria for the open vial (reconstituted) data supports the open vial claim of 14 days when properly stored at 2–8°C.

On-board Stability: Pooled aliquots of test FT4 MCMs in sample cups were stored on the ADVIA Centaur system and measured at time point T= 0, 2, 4 and 5 hours. The sponsor's acceptance criteria for the on-board stability study were met up to 5 hours, which supports the on-board stability claim for 4 hours.

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Stability Acceptance Criteria

The sponsor's stability specifications acceptance criteria for the ADVIA Centaur FT4 MCM are as follows:

Real Time/Shelf life (Unopened): The dose recovery for MCM1 and the ● % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.
In-Use Open Vial (Reconstituted): The dose recovery for MCM1 and the ● % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.
On-Board: The dose recovery for MCM1 and the % dose recoveries for ● MCM2-7 met the sponsor's required acceptance criteria.

9.2.2 Value Assignment

The ADVIA Centaur FT4 MCMs are value assigned using assigned reference calibrators and MCMs. The assigned reference calibrators are prepared using USP (United States Pharmacopeia) T4 stock and are traceable to USP internal material. The MCMs are manufactured using qualified materials and measurement procedures.

For each new FT4 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 MCM2-7 value assignment. This consists of running alternating samples of the reference and new MCM level in the same run. MCM2-7 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 FT4 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 FT4 MCM ensure that MCM1 measures at or below the FT4 assay sensitivity limit. MCM7 targeted greater than 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

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ranges are established per the sponsor's internal procedural specifications for FT4 MCM.

ADVIA Centaur FT4 MCM levels and target values are provided in Table 2.

MCM Level	Target Values (ng/dL)
MCM1	0.00
MCM2	0.42
MCM3	0.80
MCM4	1.70
MCM5	3.0
MCM6	5.6
MCM7	13.5
Assay Range	0.1-12.0 ng/dL

Table 2: Example FT4 MCM Levels and Target Values

9.2.4 Traceability

The ADVIA Centaur FT4 assay is standardized to an internal standard manufactured using USP (United States Pharmacopeia) material. Assigned values for calibrators and MCMs are traceable to this standardization.

10. Proposed Labeling

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

11. Conclusion

The ADVIA Centaur FT4 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 FT4 CVM. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur FT4 Maser Curve Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

{18}------------------------------------------------

SIEMENS

(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® FSH, FT4, T4, and T3 Master Curve Material (MCM)

510(k) Summary – ADVIA Centaur T4 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: K143687

1. Applicant Information	Siemens Healthcare Diagnostics Inc.
Mailing Address:	511 Benedict Avenue
	Tarrytown, NY 10591 USA
Contact Person:	Fatima Pacheco
	Regulatory Clinical Affairs Specialist
Phone Number:	(914) 524-2450
Fax Number:	(914) 524-3579
E-mail Address:	fatima.pacheco@siemens.com
Date Prepared:	July 13, 2015
2. Device Name
Proprietary Name:	ADVIA Centaur® T4 Master Curve Material
Measurand:	Quality Control materials for ADVIA Centaur T4 assay
Type of Test:	Master Curve Material (MCM) for ADVIA Centaur T4 assay
Regulation Section:	21 CFR 862.1660, Quality Control Material
Classification:	Class I Reserved
Products Code:	JJX – Single (Specified) Analyte Controls (Assayed and
	Unassayed)
Panel:	Clinical Chemistry (75)
3. Predicate Device Name	Elecsys T4 Calcheck 5
Predicate 510(k) No:	K112528
4. Device Description:	ADVIA Centaur® T4 Master Curve Material is an in vitrodiagnostic product containing various levels of levothyroxine inhuman plasma with sodium azide and preservatives. Each setcontains six levels; with a reconstituted volume of 1.0 mL/vialper level. MCM1 contains no analyte. The T4 MCMs assignedvalues are lot-specific of target values: 0.00, 2.50, 5.00, 10.0,15.0. and 35.0 µg/dL.
5. Intended Use:Indication for Use:	See Indications for Use Statement below:The ADVIA Centaur® Thyroxine (T4) Master Curve Material isfor in vitro diagnostic use in the verification of calibration andreportable range of the ADVIA Centaur T4 assay.
Special Conditions forUse Statement(s):	For prescription use only
Special InstrumentRequirements:	ADVIA Centaur® SystemsA description of the ADVIA Centaur system is documented inK971418. Subsequent modifications to the instrument have beenreviewed and cleared in K032525 and K041133.
6. Technological Characteristicsand Substantial EquivalenceComparison with Predicate:	A comparison of the device features, intended use, and otherinformation demonstrates that the ADVIA Centaur T4 MCM issubstantially equivalent to the predicate device as summarizedin Table 1.

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SIMILARITIES
	Candidate Device	Predicate Device
Item	ADVIA Centaur T4 MCM	Elecsys T4 Calcheck 5
IntendedUse	The ADVIA Centaur Thyroxine (T4)MCM is for in vitro diagnostic use inthe verification of calibration andreportable range of the ADVIACentaur T4 assay.	The Elecsys T4 CalCheck 5 is an assayedcontrol for use in calibration verificationand for use in the verification of theassay range established by the Elecsys T4reagent on the indicated Elecsys andcobas e immunoassay analyzers.
Analyte	Thyroxine	Same
Form	Lyophilized	Same
Matrix	Human plasma	Human serum
Storage	2–8°C	2–8°C
DIFFERENCES
Levels	6	5
Stability	Unopened - Stable when storedunopened at 2-8°C for 10 months.	Unopened - Stored at 2-8°C until theexpiration date printed on the bottlelabels.Opened (Reconstituted) - Stable for4 hours at 20-25°C.
Use	Single Use Only	Multiple Use

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

8. Test Principle

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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 XP system to support the shelf life unopened and reconstituted material for the ADVIA Centaur T4 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 T4 MCM Instructions for Use.

The following stability studies were performed for ADVIA Centaur T4 MCM:

Real time shelf-life studies (unopened): Test T4 MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 7 months and 11 months. Real time studies are on-going at T=15 months, 19 months, 24 months. 30 months, and 31 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 to the -80°C stored reference MCM. Acceptance criteria for the real-time stability study were met up to the 11 months' time point, which supports a shelf-life claim of 10 months. Unopened storage shelf-life is indicated by the expiration date on the vial label.

Stability Acceptance Criteria

The sponsor's stability specifications acceptance criteria for the ADVIA Centaur T4 MCM are as follows:

Real Time/Shelf life (Unopened): The dose recovery for MCM1 and the % dose recoveries for MCM2-6 met the sponsor's required acceptance criteria.

9.2.2 Value Assignment

The ADVIA Centaur T4 MCMs are value assigned using assigned reference calibrators and MCMs. The assigned reference calibrators are prepared using USP (United States Pharmacopeia) T4 stock and are traceable to USP internal material. The MCMs are manufactured using qualified materials and measurement procedures.

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® FSH, FT4, T4, and T3 Master Curve Material (MCM)

For each new T4 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 MCM2-6 value assignment. This consists of running alternating samples of the reference and new MCM level in the same run. MCM2-6 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 T4 MCMs. MCM6 is expected to read above the assay range of 30.0 ug/dL, therefore the MCM6 level is also diluted 1:4 before testing. 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 ug/dL dose. MCM1 is analyte-free basepool comprising of only the matrix and preservatives. The quality control specifications and final value assignment limits for T4 MCM ensure that MCM1 measures at or below the T4 assay sensitivity limit. MCM6 targeted greater than 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 T4 MCM.

ADVIA Centaur T4 MCM levels and target values are provided in Table 2.

MCM Level	Target Values(µg/dL)
MCM1	0.00
MCM2	2.50
MCM3	5.00
MCM4	10.0
MCM5	15.0
MCM6	35.0
Assay Range	0.3–30.0 µg/dL

Table 2: Example T4 MCM Levels and Target Values

9.2.4 Traceability

The ADVIA Centaur T4 assay is standardized to an internal standard manufactured using USP (United States Pharmacopeia) material. Assigned values for calibrators and MCMs are traceable to this standardization.

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10. Proposed Labeling

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

11. Conclusion

The ADVIA Centaur T4 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 Elescys T4 Calcheck 5. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur T4 Maser Curve Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

{24}------------------------------------------------

SIEMENS

(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® FSH, FT4, T4, and T3 Master Curve Material (MCM)

510(k) Summary – ADVIA Centaur T3 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: K143687

1. Applicant Information	Siemens Healthcare Diagnostics Inc.
Mailing Address:	511 Benedict Avenue
	Tarrytown, NY 10591 USA
Contact Person:	Fatima Pacheco
	Regulatory Clinical Affairs Specialist
Phone Number:	(914) 524-2450
Fax Number:	(914) 524-3579
E-mail Address:	fatima.pacheco@siemens.com
Date Prepared:	July 13, 2015
2. Device Name
Proprietary Name:	ADVIA Centaur® T3 Master Curve Material
Measurand:	Quality Control materials for ADVIA Centaur T3 assay
Type of Test:	Master Curve Material (MCM) for ADVIA Centaur T3 assay
Regulation Section:	21 CFR 862.1660, Quality Control Material
Classification:	Class I Reserved
Products Code:	JJX - Single (Specified) Analyte Controls (Assayed and
	Unassayed)
Panel:	Clinical Chemistry (75)
3. Predicate Device Name	Elecsys T3 Calcheck 5
Predicate 510(k) No:	K111552
4. Device Description:	ADVIA Centaur® T3 Master Curve Material is an in vitrodiagnostic product containing various levels of liothyronine inhuman plasma with sodium azide and preservatives. Each secontains seven levels; with a reconstituted volume of1.0 mL/vial per level. MCM1 contains no analyte. The T3MCMs assigned values are lot-specific of target values: 0.00,0.42, 0.69, 1.11, 1.65, 3.87, and 7.00 ng/mL.
5. Intended Use:Indication for Use:	See Indications for Use Statement below:The ADVIA Centaur® Triiodothyronine (T3) Master CurveMaterial is for in vitro diagnostic use in the verification ocalibration and reportable range of the ADVIA Centaur T3assay.
Special Conditions forUse Statement(s):	For prescription use only
Special InstrumentRequirements:	ADVIA Centaur® SystemsA description of the ADVIA Centaur system is documented inK971418. Subsequent modifications to the instrument have beenreviewed and cleared in K032525 and K041133.
6. Technological Characteristicsand Substantial EquivalenceComparison with Predicate:	A comparison of the device features, intended use. and otherinformation demonstrates that the ADVIA Centaur T3 MCM issubstantially equivalent to the predicate device as summarizedin Table 1.

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SIMILARITIES
	Candidate Device	Predicate Device
Item	ADVIA Centaur T3 MCM	Elecsys T3 Calcheck 5
IntendedUse	The ADVIA CentaurTriiodothyronine (T3) MCM is for invitro diagnostic use in theverification of calibration andreportable range of the ADVIACentaur T3 assay.	The Elecsys T3 CalCheck 5 is an assayedcontrol for use in calibration verificationand for use in the verification of theassay range established by the Elecsys T3reagent on the indicated Elecsys andcobas e immunoassay analyzers.
Analyte	Triiodothyronine	Same
Form	Lyophilized	Same
Matrix	Human plasma	Human serum
Use	Multiple Use	Same
Storage	2–8°C	2–8°C
DIFFERENCES
Levels	7	5
Stability	Unopened – Stable when storedunopened at 2–8°C for 10 months.Opened (Reconstituted) – Stablewhen stored at 2–8°C for 21days; oron-board for 4 hours.	Unopened - Stored at 2–8°C until theexpiration date printed on the bottlelabels.Opened (Reconstituted) – Stable for 4hours at 20–25°C.

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

8. Test Principle

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® FSH, FT4, T4, and T3 Master Curve Material (MCM)

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 XP system to support the shelf life unopened and reconstituted material for the ADVIA Centaur T3 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 T3 MCM Instructions for Use.

The following stability studies were performed for ADVIA Centaur T3 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 T3 MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 7 months and 11 months. Real time studies are on-going at T=15 months, 19 months, 24months, 30 months, and 31 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 to the -80°C stored reference MCM. The sponsor's acceptance criteria for the real-time stability study were met up to the 11 months' time point, which supports a shelflife claim of 10 months. Unopened storage shelf-life is indicated by the expiration date on the vial label.

In-Use Open Vial (Reconstituted): Test T3 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. The sponsor's acceptance criteria for the open vial (reconstituted) stability study were met to the 22 days' time point, which supports the open vial claim of 21 days when properly stored at 2-8°C.

On-board Stability: Pooled aliquots of test T3 MCMs in sample cups were stored on the ADVIA Centaur system and measured at time point T= 0. 2, 4 and 5 hours. The sponsor's acceptance criteria for the on-board stability study were met up to 5 hours, which supports the on-board stability claim for 4 hours.

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Stability Acceptance Criteria

The sponsor's stability specifications acceptance criteria for the ADVIA Centaur T3 MCM are as follows:

Real Time/Shelf life (Unopened): The dose recovery for MCM1 and the . % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.
In-Use Open Vial (Reconstituted): The dose recovery for MCM1 and the ● % dose recoveries for MCM2-7 met the sponsor's required acceptance criteria.
On-Board: The dose recovery for MCM1 and the % dose recoveries for . MCM2-7 met the sponsor's required acceptance criteria.

9.2.2 Value Assignment

The ADVIA Centaur T3 MCMs are value assigned using assigned reference calibrators and MCMs. The assigned reference calibrators are prepared using USP (United States Pharmacopeia) T3 stock and are traceable to USP internal material. The MCMs are manufactured using qualified materials and measurement procedures.

For each new T3 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 MCM2-7 value assignment. This consists of running alternating samples of the reference and new MCM level in the same run. MCM2-7 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 T3 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 T3 MCM ensure that MCM1 measures at or below the T3 assay sensitivity limit.

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9.2.3 Expected Values

ADVIA Centaur T3 MCM levels and target values are provided in Table 2.

MCM Level	Target Values(ng/mL)
MCM1	0.00
MCM2	0.42
MCM3	0.69
MCM4	1.11
MCM5	1.65
MCM6	3.87
MCM7	7.00
Assay Range	0.1-8 ng/mL

Table 2: Example T3 MCM Levels and Target Values

9.2.4 Traceability

The ADVIA Centaur T3 assay is standardized to an internal standard manufactured using USP (United States Pharmacopeia) material. Assigned values for calibrators and MCMs are traceable to this standardization.

10. Proposed Labeling

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

11. Conclusion

The ADVIA Centaur T3 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 Elescys T3 Calcheck 5. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur T3 Maser Curve Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
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.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.