ADIVA Centaur Prolactin Master Curve Material (MCM), ADIVA Centaur Cortisol Master Curve Material (MCM) by SIEMENS HEALTHCARE DIAGNOSTICS, INC.

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

Device Description

ADVIA Centaur® Prolactin Master Curve Material is an in vitro diagnostic product containing various levels of prolactin spiked in lyophilized equine serum with sodium azide (0.1%) and preservatives including amphotericin B. Each set contains ten levels (MCM1–10); with a reconstituted volume of 1.0 mL per level. MCM1contains no analyte. The MCMs assigned values are lot-specific of target values: 0.00, 2.11, 4.61, 9.21, 26.0, 51.1, 82.9, 113, 161, and 218 ng/mL.
ADVIA Centaur® Cortisol Master Curve Materials is an in vitro diagnostic product containing various levels of cortisol in lyophilized human plasma with sodium azide. Each set contains seven lyophilized levels (MCM1-7); with a reconstituted volume of 1.0 mL each. MCM1 contains no analyte. The COR MCMs assigned values are lot-specific of target values: 0.00, 1.00, 2.00, 6.00, 12.0, 30.0, and 80.0 µg/dL.

AI/ML Overview

The provided text describes the acceptance criteria and supporting studies for two Master Curve Materials (MCMs): ADVIA Centaur Prolactin (PRL) MCM and ADVIA Centaur Cortisol (COR) MCM. These materials are intended for in vitro diagnostic use in verifying the calibration and reportable range of their respective assays.

Here's a breakdown of the requested information:

ADVIA Centaur Prolactin (PRL) Master Curve Material

1. Table of acceptance criteria and reported device performance:

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Stability
Real Time/Shelf Life (Unopened)	Dose recovery for MCM1 and % dose recovery for MCM2-10 met the requirements of the acceptance criteria and no adverse trends.	Met up to the 30 months' time point, supporting a shelf-life claim of 29 months when stored at 2-8°C.
In-Use Open Vial (Reconstituted)	Dose recovery for MCM1 and the % dose recovery MCM2-10 met the requirements of the acceptance criteria.	Met to the 29 days' time point, supporting an open vial claim of 28 days when properly stored at 2-8°C.
On-Board	Dose recovery for MCM1 and the % dose recovery for MCM2-10 met the requirements of the acceptance criteria.	Met up to 5 hours, supporting an on-board stability claim for 4 hours.
Value Assignment	MCM1 measures at or below the PRL assay sensitivity limit. New MCM doses fall within the final value assignment specification for PRL MCMs. Mean MCM doses of the new MCM lot fall within the customer range specifications.	MCM1 target is 0.0 dose and is analyte-free. MCMs are manufactured using qualified materials and measurement procedures. New MCM doses are calculated based on the relationship between observed reference MCM dose and its assigned value using a two-point calibration. Performance verification runs ensure mean MCM doses fall within customer range specifications. (Specific quantitative results for individual lots are lot-specific as shown in Table 2, page 9).
Expected Values	Lot-specific assigned values and lot-specific customer ranges established per % interval (MCM1: N/A, MCM2: 40%, MCM3-MCM9: 25%, MCM10: 20%).	Example lot-specific target and assigned values are provided, demonstrating adherence to the defined intervals (e.g., Table 2). The assay range is 0.3–200 ng/mL.
Traceability	The ADVIA Centaur Prolactin assay is traceable to World Health Organization (WHO) 3rd IRP for Prolactin (84/500). Assigned values for calibrators and MCMs are traceable to this standardization. The PRL MCMs are manufactured using qualified materials and measurement procedures.	The PRL MCMs are traceable to WHO 3rd IRP for Prolactin (84/500) through internal material standardized against it. MCMs are manufactured using qualified materials and measurement procedures.

2. Sample size used for the test set and the data provenance:

Real Time/Shelf Life (unopened): Test PRL MCMs stored unopened. Tested at T=0, 12 months, and 30 months. The sample size for each time point is not explicitly stated in terms of number of individual units, but it's implied that multiple samples were tested to establish dose recovery.
In-Use Open Vial (reconstituted): Reconstituted PRL MCMs, 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. (10 levels * 5 replicates * 6 time points = 300 measurements total, minimum).
On-Board Stability: Pooled aliquots of test PRL MCMs in sample cups. Measured at T=0, 2, 4, and 5 hours. Sample size not explicitly stated for number of individual units, but likely multiple measurements per time point.
Value Assignment Test Set: For a new PRL MCM lot, MCM1 is run in 5 replicates on two separate runs. MCM2-MCM10 were tested on 20 replicates in total (one run and four sample cups run in 5 replicates). Performance verification run used 6 replicates of each MCM level.
Data Provenance: The studies were conducted by Siemens Healthcare Diagnostics, Inc. The data is retrospective for the purpose of demonstrating the device's performance for this 510(k) submission. Country of origin not explicitly stated, but the manufacturer is based in the USA.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
Not applicable. These are in vitro diagnostic materials used for calibration verification, not for making clinical diagnoses based on subjective expert review. The "ground truth" for the MCMs is established by their formulation (analyte-free for MCM1, spiked levels for others) and traceability to recognized standards (WHO 3rd IRP for Prolactin 84/500) and internal reference materials.

4. Adjudication method for the test set:
Not applicable for this type of device and study. Performance is assessed against quantitative, pre-defined acceptance criteria, not through expert adjudication of results.

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:
Not applicable. This is an in vitro diagnostic (IVD) material, not an AI-powered diagnostic device, and therefore no MRMC study was performed.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Not applicable. This is an IVD material, not an algorithm. Its performance is evaluated intrinsically through stability and value assignment studies on an automated analyzer (ADVIA Centaur system).

7. The type of ground truth used:
The ground truth for the PRL MCMs is primarily based on:

Traceability to International Standards: Specifically, the World Health Organization (WHO) 3rd International Reference Preparation (IRP) for human Prolactin 84/500.
Analytical Procedures: MCMs are manufactured using qualified materials and measurement procedures, and for MCMs 2-10, known concentrations of prolactin are spiked into a matrix. MCM1 is analyte-free basepool.
Value Assignment: Reference calibrators are prepared using Prolactin stock traceable to the WHO standard. The MCMs are value assigned against these reference calibrators using a nested testing run protocol to account for system and run variation.

8. The sample size for the training set:
Not applicable. This is an IVD material, not an AI model that requires a training set.

9. How the ground truth for the training set was established:
Not applicable.

ADVIA Centaur Cortisol (COR) Master Curve Material

1. Table of acceptance criteria and reported device performance:

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Stability
Real Time/Shelf Life (Unopened)	Dose recovery for MCM1 and % dose recovery for MCM2-7 met the requirements of the acceptance criteria and no adverse trends.	Met up to the 23 months' time point, supporting a shelf-life claim of 22 months when stored at 2-8°C.
In-Use Open Vial (Reconstituted)	Dose recovery for MCM1 and % dose recovery for MCM2-7 met the requirements of the acceptance criteria.	Met to the 15 days' time point, supporting an open vial claim of 14 days when properly stored at 2-8°C.
On-Board	Dose recovery for MCM1 and % dose recovery for MCM2-7 met the requirements of the acceptance criteria.	Met up to 5 hours, supporting an on-board stability claim for 4 hours.
Value Assignment	MCM1 measures at or below the Cortisol assay sensitivity limit. New MCM doses fall within the final value assignment specification for COR MCMs. Mean MCM doses of the new MCM lot fall within the customer range specifications.	MCM1 target is 0.0 dose and is analyte-free. MCMs are manufactured using qualified materials and measurement procedures. New MCM doses are calculated based on the relationship between observed reference MCM dose and its assigned value using a two-point calibration. Performance verification runs ensure mean MCM doses fall within customer range specifications. (Specific quantitative results for individual lots are lot-specific as shown in Table 2, page 16).
Expected Values	Lot-specific assigned values and lot-specific customer ranges established per % interval (MCM1: N/A, MCM2: 35%, MCM3-MCM6: 30%, MCM7: 20%).	Example lot-specific target and assigned values are provided, demonstrating adherence to the defined intervals (e.g., Table 2). The assay range is 0.20–75 µg/dL.
Traceability	The ADVIA Centaur Cortisol assay is standardized using internal standards manufactured analytically which are traceable to gas chromatography-mass spectroscopy (GCMS). Assigned values for calibrators and MCMs are traceable to this standardization. The COR MCMs are manufactured using qualified materials and measurement procedures.	The COR MCMs are traceable to gas chromatography-mass spectroscopy (GCMS) through analytically prepared internal materials. MCMs are manufactured using qualified materials and measurement procedures.

2. Sample size used for the test set and the data provenance:

Real Time/Shelf Life (unopened): Test COR MCMs stored unopened. Tested at T=0, 12 months, 18 months, and 23 months. The sample size for each time point is not explicitly stated in terms of number of individual units, but it's implied that multiple samples were tested to establish dose recovery.
In-Use Open Vial (reconstituted): Reconstituted COR MCMs, each level pooled, aliquotted, and stored at 2-8°C. Tested in 5 replicates per level at T=0, 2, 4, 7, 11, 14, and 15 days. (7 levels * 5 replicates * 7 time points = 245 measurements total, minimum).
On-Board Stability: Pooled aliquots of test COR MCMs in sample cups. Measured at T=0, 2, 4, and 5 hours. Sample size not explicitly stated for number of individual units, but likely multiple measurements per time point.
Value Assignment Test Set: For a new COR MCM lot, MCM1 is run in 5 replicates on two separate runs. MCM2-MCM7 were tested on 20 replicates in total (one run and four sample cups run in 5 replicates). Performance verification run used 6 replicates of each MCM level.
Data Provenance: The studies were conducted by Siemens Healthcare Diagnostics, Inc. The data is retrospective for the purpose of demonstrating the device's performance for this 510(k) submission. Country of origin not explicitly stated, but the manufacturer is based in the USA.

7. The type of ground truth used:
The ground truth for the COR MCMs is primarily based on:

Traceability to Reference Methods: Specifically, gas chromatography-mass spectroscopy (GCMS) through analytically prepared internal standards.
Analytical Procedures: MCMs are manufactured using qualified materials and measurement procedures, and for MCMs 2-7, known concentrations of cortisol are spiked into a matrix. MCM1 is analyte-free basepool.
Value Assignment: Reference calibrators are prepared using cortisol stock traceable to GCMS. The MCMs are value assigned against these reference calibrators using a nested testing run protocol to account for system and run variation.

8. The sample size for the training set:
Not applicable. This is an IVD material, not an AI model that requires a training set.

9. How the ground truth for the training set was established:
Not applicable.

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features three human profiles facing right, connected by a wavy line. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.

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

December 5, 2014

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

Re: K143194

Trade/Device Name: ADVIA Centaur® Prolactin Master Curve Material (MCM), ADVIA Centaur® Cortisol Master Curve Material (MCM) Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I. Reserved Product Code: JJX Dated: October 31, 2014 Received: November 6, 2014

Dear Ms. 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 as set 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.

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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,

Stayce Beck -S

For : 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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Indications for Use

510(k) Number (if known) K143194

Device Name

ADVIA Centaur® Prolactin Master Curve Material (MCM)

Indications for Use (Describe)

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

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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Indications for Use

510(k) Number (if known) K143194

Device Name

ADVIA Centaur® Cortisol Master Curve Material (MCM)

Indications for Use (Describe)

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

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

Section 006: 510(k) Summary

510(k) Summary – ADVIA Centaur Prolactin 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: K143194

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:	November 25, 2014
2. Device Name	ADVIA Centaur® Prolactin (PRL) Master Curve Material
Proprietary Name:	Quality Control materials for ADVIA Centaur PRL assay
Measurand:	Master Curve Material (MCM) for ADVIA Centaur PRL assay
Type of Test:	21 CFR 862.1660, Quality Control Material
Regulation Section:	Class I Reserved
Classification:	JJX – Single (Specified) Analyte Controls (Assayed andUnassayed)
Products Code:	Clinical Chemistry (75)
Panel:	Elecsys Prolactin II CalCheck 5K110613
3. Predicate Device NamePredicate 510(k) No:	ADVIA Centaur® Prolactin Master Curve Material is anin vitro diagnostic product containing various levels of prolactinspiked in lyophilized equine serum with sodium azide (0.1%)and preservatives including amphotericin B. Each set containsten levels (MCM1–10); with a reconstituted volume of 1.0 mLper level. MCM1contains no analyte. The MCMs assignedvalues are lot-specific of target values: 0.00, 2.11, 4.61, 9.21,26.0, 51.1, 82.9, 113, 161, and 218 ng/mL.
4. Device Description:

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(Bundled) Abbreviated 510(k) Premarket Notification

ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

5. Intended Use:Indication for Use:	See Indications for Use Statement below:The ADVIA Centaur® Prolactin (PRL) Master Curve Material isfor in vitro diagnostic use in the verification of calibration andreportable range of the ADVIA Centaur Prolactin assay.
Special Conditions forUse Statement(s):	For prescription use only
Special InstrumentRequirements:	ADVIA Centaur® SystemsA description of the ADVIA Centaur system is documentedin K971418. Subsequent modifications to the instrument havebeen reviewed 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 PRL MCMis substantially equivalent to the predicate device assummarized in Table 1.

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

SIMILARITIES
	Candidate Device	Predicate Device
Item	ADVIA Centaur PRL MCM	Elecsys Prolactin II CalCheck 5
IntendedUse	The ADVIA Centaur Prolactin (PRL)Master Curve Material is for in vitrodiagnostic use in the verification ofcalibration and reportable range of theADVIA Centaur Prolactin assay.	The Elecsys Prolactin II CalCheck 5is an assayed control for usein calibration verification and for usein the verification of the assayrange established by the ElecsysProlactin II reagent on the indicatedElecsys and cobas e immunoassayanalyzers.
Analyte	Prolactin	Same
Use	Multiple Use	Same
Storage	2–8°C	Same
Form	Lyophilized	Same
Matrix	Equine serum	Same
DIFFERENCES
Levels	10	5
Stability	Unopened – Stable when storedunopened at 2-8°C for 29 months.Opened (Reconstituted) – Stablewhen stored at 2–8°C for 28 days; oron-board for 4 hours.	Unopened - Stable at 2-8°C up tothe expiration date printed on thebottle labels.Reconstituted – Stable for 4 hours at20-25°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

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

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

The following studies were conducted on the ADVIA Centaur XP system.

9.2.1 Stability Studies

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

The following stability studies were performed for ADVIA Centaur PRL 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 PRL MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 12 months, and 30 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 T=0 dose recovery results. Acceptance criteria for the real-time stability study were met up to the 30 months' time point, which supports a shelf-life claim of 29 months. Storage shelflife (unopened) at 2-8°C is indicated by the expiration date on the vial label.

In-Use Open Vial (Reconstituted): Test PRL 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. 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 PRL 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. 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 PRL MCM are as follows:

Real Time/Shelf life (Unopened): The dose recovery for MCM1 and . % dose recovery for MCM2-10 met the requirements of the acceptance criteria and no adverse trends.
In-Use Open Vial (Reconstituted): The dose recovery for MCM1 and the % dose recovery MCM2-10 met the requirements of the acceptance criteria.
. On-Board: The dose recovery for MCM1 and the % dose recovery for MCM2-10 met the requirements of the acceptance criteria.

9.2.2 Value Assignment

The ADVIA Centaur PRL MCMs are value assigned using assigned reference calibrators and MCMs. The assigned reference calibrators are prepared using Prolactin stock and are traceable to internal material which is standardized against World Health Organization (WHO) 3td IRP for human Prolactin 84/500 reference material. The MCMs are manufactured using qualified materials and measurement procedures.

For each new PRL MCM lot manufactured, MCM1 is run in 5 replicates on two separate runs using one reagent kit lot. A nested testing run protocol is used for MCM2-MCM10 value assignment. This consists of running alternating samples of the reference and new MCM level in the same run. MCM2-MCM10 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 PRL 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 PRL MCM ensure that MCM1 measures at or below the PRL assay sensitivity limit. MCM10 targeted greater

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

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 % interval as below.

MCM Level	% Interval
MCM1	N/A
MCM2	40%
MCM3	25%
MCM4	25%
MCM5	25%
MCM6	25%
MCM7	25%
MCM8	25%
MCM9	25%
MCM10	20%

Example Lot-specific target and assigned values are provided in the ADVIA Centaur PRL MCM lot-specific value sheet in the example provided in Table 2.

MCM level	Target Values(ng/mL)	Assigned Values(ng/mL)
MCM1	0.00	0.00
MCM2	2.11	2.02
MCM3	4.61	5.21
MCM4	9.21	9.09
MCM5	26.0	25.9
MCM6	51.1	52.0
MCM7	82.9	87.4
MCM8	113	124
MCM9	161	148
MCM10	218	243
Assay Range	0.3–200 ng/mL

Table 2: Example Lot-specific PRL MCM Target and Assigned Values

9.2.4 Traceability

The ADVIA Centaur Prolactin assay is traceable to World Health Organization (WHO) 3te IRP for Prolactin (84/500). Assigned values for calibrators and MCMs are traceable to this standardization. The PRL MCMs are manufactured using qualified materials and measurement procedures.

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

10. Proposed Labeling

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

11. Conclusion

The ADVIA Centaur PRL 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 Elecsys Prolactin II CalCheck 5. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur PRL 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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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

510(k) Summary – ADVIA Centaur COR 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: K143194

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:	November 25, 2014
2. Device Name	ADVIA Centaur® COR Master Curve Material
Proprietary Name:Measurand:Type of Test:	Quality Control materials for ADVIA Centaur COR assayMaster Curve Material (MCM) for ADVIA Centaur COR 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 NamePredicate 510(k) No:	Elecsys Cortisol CalCheckK000576
4. Device Description:	ADVIA Centaur® Cortisol Master Curve Materials is an in vitrodiagnostic product containing various levels of cortisol inlyophilized human plasma with sodium azide. Each set containsseven lyophilized levels (MCM1-7); with a reconstitutedvolume of 1.0 mL each. MCM1 contains no analyte. The CORMCMs assigned values are lot-specific of target values: 0.00,1.00, 2.00, 6.00, 12.0, 30.0, and 80.0 µg/dL.
5. Intended Use:Indication for Use:	See Indications for Use Statement below:The ADVIA Centaur® Cortisol (COR) Master Curve Material isfor in vitro diagnostic use in the verification of calibration andreportable range of the ADVIA Centaur Cortisol 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 havebeen reviewed and cleared in K032525 and K041133.

Section 006, Page 8 of 13

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

1. Technological Characteristics and Substantial Equivalence Comparison with Predicate:
  A comparison of the device features, intended use, and other information demonstrates that the ADVIA Centaur COR MCM substantially equivalent to the predicate device as is summarized in Table 1.

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

SIMILARITIES
	Candidate Device	Predicate Device
Item	ADVIA Centaur COR MCM	Elecsys Cortisol CalCheck
IntendedUse	The ADVIA Centaur Cortisol (COR)MCM is for in vitro diagnostic use inthe verification of calibration andreportable range of the ADVIACentaur Cortisol assay.	For use in the verification of thecalibration established by the ElecsysCortisol reagent on the indicated Elecsysand cobas e immunoassay analyzers.
Analyte	Cortisol	Same
Use	Multiple Use	Same
Storage	2–8°C	Same
Form	Lyophilized	Same
DIFFERENCES
Matrix	Human Plasma	Human Serum
Levels	7	3
Stability	Unopened – Stable when storedunopened at 2-8°C for 22 months;Opened (Reconstituted) – Stablewhen stored at 2–8°C for 14 days; oron-board for 4 hours	Unopened - Stable at 2-8°C up to theexpiration date printed on the bottlelabels.Opened (Reconstituted) - Stable for4 hours 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® Prolactin and Cortisol 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 ●
Assav cut-off ●
Method Comparison Studies ●
Clinical Studies (Sensitivity, Specificity, and cut-off)

9.2 Non-Clinical Performance Testing

The following studies were conducted on the ADVIA Centaur XP system.

9.2.1 Stability Studies

Stability studies were conducted to support the shelf life unopened and reconstituted material for the ADVIA Centaur COR 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 COR MCM Instructions for Use.

The following stability studies were performed for ADVIA Centaur COR 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 COR MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 12 months, 18 months, and 23 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 T=0 dose recovery results. Acceptance criteria for the real-time stability study were met up to the 23 months' time point, which supports a shelf-life claim of 22 months. Unopened storage shelf-life is indicated by the expiration date on the vial label.

In-Use Open Vial (Reconstituted): Test COR MCMs were reconstituted, each level pooled, aliquotted and stored at 2-8°C, tested in 5 replicates per level at T=0, 2, 4, 7, 11, 14, and 15 days. Acceptance criteria for the open vial (reconstituted) stability study were met to the 15 days' time point, which supports the open vial claim of 14 days when properly stored at 2-8°C.

On-board Stability: Pooled aliquots of test COR MCMs in sample cups were stored on the ADVIA Centaur system and measured at time point T= 0, 2, 4 and 5

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

hours. 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 COR MCM are as follows:

. Real Time/Shelf life (Unopened): The dose recovery for MCM1 and % dose recovery for MCM2-7 met the requirements of the acceptance criteria and no adverse trends.
. In-Use Open Vial (Reconstituted): The dose recovery for MCM1 and % dose recovery for MCM2-7 met the requirements of the acceptance criteria.
On-Board: The dose recovery for MCM1 and % dose recovery for MCM2-7 ● met the requirements of the acceptance criteria.

9.2.2 Value Assignment

The ADVIA Centaur COR MCMs are value assigned using assigned reference calibrators and MCMs. The assigned reference calibrators are prepared using cortisol stock traceable analytically prepared internal material which is traceable gas-chromatography-mass spectroscopy (GCMS). The MCMs to are manufactured using qualified materials and measurement procedures.

For each new COR MCM lot manufactured. MCM1 is run in 5 replicates on two separate runs using one reagent kit lot. 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 COR 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 COR MCM ensure that MCM1 measures at or below the Cortisol assay sensitivity limit. MCM7 targeted greater than the assay range is diluted with the MCM1 to meet the reportable range of the assay.

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(Bundled) Abbreviated 510(k) Premarket Notification ADVIA Centaur® Prolactin and Cortisol Master Curve Material (MCM)

9.2.3 Expected Values

MCM Level	% Interval
MCM1	N/A
MCM2	35
MCM3	30
MCM4	30
MCM5	30
MCM6	30
MCM7	20

Example Lot-specific target and assigned values are provided in the ADVIA Centaur COR MCM lot-specific value sheet in the example provided in Table 2.

MCM Level	Target Values(µg/dL)	Assigned Values(µg/dL)
MCM1	0.00	0.0
MCM2	1.00	1.17
MCM3	2.00	1.96
MCM4	6.00	6.99
MCM5	12.0	12.5
MCM6	30.0	27.1
MCM7	80.0	80.3
Assay Range	0.20–75 µg/dL

Table 2: Example Lot-specific COR MCM Target and Assigned Values

9.2.4 Traceability

The ADVIA Centaur Cortisol assay is standardized using internal standards manufactured analytically which are traceable to gas chromatography-mass spectroscopy (GCMS). Assigned values for calibrators and MCMs are traceable to this standardization. The COR 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 COR 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 Elecsys Cortisol CalCheck. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur COR 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.