ADVIA Centaur C-peptide (CpS) Master Curve Material (MCM), ADVIA Centaur Insulin (IRI) Master Curve Material (MCM) by SIEMENS HEALTHCARE DIAGNOSTICS, INC.

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

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

Device Description

ADVIA Centaur® C-peptide Master Curve Material is an in vitro diagnostic product containing various levels of C-peptide spiked in citric acid buffer with casein and preservatives. Each set contains ten levels (MCM1–10); ready-to-use 1.0 mL per level. MCM1 contains no analyte. The MCMs assigned values are lot-specific of target values 0.0 0.14, 0.25, 0.55, 1.05, 2.05, 4.00, 8.00, 16.0, 32.5 ng/mL.

ADVIA Centaur® Insulin Master Curve Materials is an in vitro diagnostic product containing various levels of insulin in buffered saline with casein, potassium thiocyanate (3.89%), sodium azide (<0.1%), and preservatives. Each set contains ten levels (MCM1-10); ready-to-use 1.0 mL per level. MCM1 contains no analyte. The IRI MCMs assigned values are lotspecific of target values: 0.0, 2.5, 4.5, 10.0, 20.0, 39.0, 79.0, 158, 225, and 300 mU/L.

AI/ML Overview

The provided document describes the Siemens ADVIA Centaur C-peptide (CpS) Master Curve Material (MCM) and ADVIA Centaur Insulin (IRI) Master Curve Material (MCM). These devices are described as in vitro diagnostic products for the verification of calibration and reportable range of their respective assays. The document focuses on establishing substantial equivalence to predicate devices and describes relevant performance characteristics, primarily stability and value assignment.

Here's an analysis of the acceptance criteria and supporting studies based on the provided text:

Device Type: In vitro diagnostic Master Curve Material (MCM) - these are control materials used to verify the calibration and reportable range of an assay, not a diagnostic device that produces patient-specific results. Therefore, the questions related to clinical performance (e.g., diagnostic accuracy metrics like sensitivity, specificity, PPV, NPV), multi-reader multi-case studies, human reader improvement with AI, and specific ground truth types like pathology or outcomes data are not applicable in the context of this device and the provided documentation. The "performance" here refers to the stability and accurate value assignment of the control material itself.

1. Acceptance Criteria and Reported Device Performance

For ADVIA Centaur C-peptide (CpS) Master Curve Material (MCM):

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Real Time/Shelf Life (Unopened) Stability	- MCM1 dose recovery: < 0.15 ng/mL- MCM2 dose recovery: 85% to 115% of T=0 dose recovery- MCM3-10 dose recovery: 88% to 112% of T=0 dose recovery- No adverse trends	Met up to 13-month time point, supporting a 12-month shelf-life claim.
On-Board Stability	- MCM1 dose recovery: ≤ 0.15 ng/mL- MCM2 dose recovery: 85% to 115% of T=0 dose recovery- MCM3-10 dose recovery: 88% to 112% of T=0 dose recovery	Met up to 5 hours, supporting a 4-hour on-board stability claim.
Value Assignment (General)	- Average dose for in-house/commercial controls: Within +/-10% of assigned targets- Ratio of in-house control RLUs to Standard 1 RLUs: Within 25-65	Stated that the average dose values obtained are the new MCM dose values (target), and these new MCM doses must fall within the target range for each MCM level as outlined in the table. Implied compliance.
Value Assignment (Specific Targets)	MCM1: < 0.06 ng/mLMCM2: 0.10–0.18 ng/mLMCM3: 0.20–0.30 ng/mLMCM4: 0.40–0.70 ng/mLMCM5: 0.80–1.30 ng/mLMCM6: 1.70–2.40 ng/mLMCM7: 3.50–4.50 ng/mLMCM8: 7.00–9.00 ng/mLMCM9: 14.0–18.0 ng/mLMCM10: 30.0–35.0 ng/mL	The document states "The new MCM doses must fall within the target range for each MCM level as outlined in Table 1." (Table 1 refers to the target range table). Implied compliance.

For ADVIA Centaur Insulin (IRI) Master Curve Material (MCM):

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Real Time/Shelf Life (Unopened) Stability	- MCM1 dose recovery: ≤ 1.5 mU/L- MCM2 dose recovery: 85% to 115% of T=0 dose recovery- MCM3-10 dose recovery: 88% to 112% of T=0 dose recovery- No adverse trends	Met up to 12-month time point, supporting an 11-month shelf-life claim.
On-Board Stability	- MCM1 dose recovery: ≤ 1.5 mU/L- MCM2 dose recovery: 85% to 115% of T=0 dose recovery- MCM3-10 dose recovery: 88% to 112% of T=0 dose recovery	Met up to 9 hours, supporting an 8-hour on-board stability claim.
Value Assignment (General)	- Average dose for commercial controls: Within +/-10% of assigned targets- Coefficient of variation (CV) from commercial controls: Within 10%	Stated that the average dose values obtained are the new MCM dose values (target), and these new MCM doses must fall within the target range for each MCM level as outlined in the table. Implied compliance.
Value Assignment (Specific Targets)	MCM1: < 0.50 mU/LMCM2: 2.00-3.00 mU/LMCM3: 4.00-5.00 mU/LMCM4: 9.00-11.0 mU/LMCM5: 18.0-22.0 mU/LMCM6: 35.0-43.0 mU/LMCM7: 71.0-87.0 mU/LMCM8: 142-173 mU/LMCM9: 200-250 mU/LMCM10: 300-360 mU/L	The document states "The new MCM doses must fall within the target range for each MCM level as outlined in Table 1." (Table 1 refers to the target range table). Implied compliance.

2. Sample Size Used for the Test Set and Data Provenance

The document does not explicitly define a "test set" in the context of clinical or diagnostic performance, as the device is a control material. Instead, testing involves stability studies and value assignment.

Sample Size for Stability Studies:
- C-peptide MCM: For each MCM level, 3 replicates were run at each time point (T=0, 3, 9, 12, 13 months for real-time; T=0, 2, 4, 5 hours for on-board).
- Insulin MCM: For each MCM level, 3 replicates were run at each time point (T=0, 3, 7, 9, 12 months for real-time; T=0, 2, 4, 6, 8, 9 hours for on-board).
Sample Size for Value Assignment:
- C-peptide MCM: MCM1-10 are run in 3 replicates across two ADVIA Centaur instruments using two reagent kit lots, run twice on each instrument. This totals 24 replicates per MCM level (3 replicates * 2 instruments * 2 reagent lots * 2 runs). Additionally, MCM9 is run diluted 1:2 using MCM1. Three levels of commercially available controls and two levels of in-house controls are used.
- Insulin MCM: MCM1-10 are run in replicates of three across two ADVIA Centaur instruments using two reagent kit lots, run twice on each instrument. This totals 24 replicates per MCM level. MCM10 is also run diluted 1:2 using MCM1. Two lots of commercially available controls (3 levels each) are used.
Data Provenance: The document does not specify the country of origin for the data or whether it is retrospective or prospective. Given the nature of stability and value assignment studies for an in-house manufactured control material, it is highly likely that these studies were conducted prospectively by the manufacturer (Siemens Healthcare Diagnostics Inc., based in Tarrytown, NY, USA).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This information is not applicable as the devices are control materials for assay calibration verification. The "ground truth" here is the assigned value of the control material, which is established through a standardized value assignment process rather than expert interpretation of clinical data.

4. Adjudication Method for the Test Set

This is not applicable as there is no "test set" in the sense of a collection of cases requiring interpretation or adjudication. The studies involve objective measurements of analyte concentration in control materials.

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

This is not applicable. The device is a control material, not an AI-powered diagnostic system or an imaging device designed for human reader interpretation. No human-in-the-loop performance is being evaluated.

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

This is not applicable. The device is a physical control material used in conjunction with an immunoassay analyzer. It does not involve an algorithm working in "standalone" mode.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

For both the C-peptide and Insulin MCMs, the "ground truth" (or reference value) is established through traceability to World Health Organization (WHO) international reference materials.

C-peptide MCM: Traceable to WHO IS 84/510 reference material.
Insulin MCM: Traceable to WHO 1st IRP 66/304 reference material.

The assigned values for master curve standards, calibrators, and MCMs are directly traceable to these international standards.

8. The Sample Size for the Training Set

This is not applicable. As a control material, there is no "training set" in the machine learning sense. The devices are manufactured according to specifications and their performance (stability and assigned values) is evaluated. The "value assignment" process could be considered analogous to establishing the expected values for the controls, but it's not a training phase for an algorithm.

9. How the Ground Truth for the Training Set Was Established

This is not applicable for the reasons outlined in point 8. The ground truth for the value assignment of the MCMs themselves is established through traceability to WHO international reference materials, as described in point 7.

Summary

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

October 29, 2014

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

Re: K142864

Trade/Device Name: ADVIA Centaur C-peptide (CpS) Master Curve Material (MCM) ADVIA Centaur Insulin (IRI) Master Curve Material (MCM) Regulation Number: 21 CFR 862.1660 Regulation Name: Single (Specified) Analyte Controls (Assayed and Unassayed) Regulatory Class: Class I, Reserved Product Code: JJX Dated: September 30, 2014 Received: October 01, 2014

Dear Ms. Fátima Pacheco:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical

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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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

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

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

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

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

Sincerely yours,

Courtney H. 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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Indications for Use

510(k) Number (if known) K142864

Device Name

ADVIA Centaur® C-peptide Master Curve Material (MCM)

Indications for Use (Describe)

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

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

ك Prescription Use (Part 21 CFR 801 Subpart D)

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

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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) K142864

Device Name

ADVIA Centaur® Insulin Master Curve Material (MCM)

Indications for Use (Describe)

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

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

ك Prescription Use (Part 21 CFR 801 Subpart D)

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

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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."

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

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510(k) Summary

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: K142864

1. Applicant Information	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:	October 23, 2014
2. Device Name
Proprietary Name:	ADVIA Centaur® C-peptide (CpS) Master Curve Material
Measurand:	Quality Control materials for ADVIA Centaur CpS assay
Type of Test:	Master Curve Material (MCM) for ADVIA Centaur CpS 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	Elecsys C-Peptide CalCheck 5
Predicate 510(k) No:	K100810
4. Device Description:	ADVIA Centaur® C-peptide Master Curve Material is anin vitro diagnostic product containing various levels ofC-peptide spiked in citric acid buffer with casein andpreservatives. Each set contains ten levels (MCM1–10);ready-to-use 1.0 mL per level. MCM1 contains no analyte.The MCMs assigned values are lot-specific of target values 0.00.14, 0.25, 0.55, 1.05, 2.05, 4.00, 8.00, 16.0, 32.5 ng/mL.
5. Intended Use:	See Indications for Use Statement below:
Indication for Use:	The ADVIA Centaur® C-peptide (CpS) Master Curve Materialis for in vitro diagnostic use in the verification of calibrationand reportable range of the ADVIA Centaur C-peptide 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 CpS MCMis substantially equivalent to the predicate device assummarized in Table 1.

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SIMILARITIES
	Candidate Device	Predicate Device
Item	ADVIA Centaur CpS MCM	Elecsys C-Peptide CalCheck 5
IntendedUse	The ADVIA Centaur C-peptide (CpS)Master Curve Material is for in vitrodiagnostic use in the verification ofcalibration and reportable range of theADVIA Centaur C-peptide assay.	The Elecsys C-Peptide CalCheck 5 isan assayed control for use incalibration verification and for use inthe verification of the serum andplasma assay range established by theElecsys C-Peptide reagent on theindicated Elecsys and cobas eimmunoassay analyzers.
Analyte	C-peptide	Same
Use	Multiple Use	Same
Storage	2-8°C	Same
DIFFERENCES
Form	Liquid	Lyophilized
Matrix	Citric acid buffered casein	HEPES buffered equine serum matrix
Levels	10	5
Stability	Unopened – Stable when storedunopened at 2-8°C for 12 months.Opened - Stable on-board for 4 hours.	Unopened - Stable at 2-8°C for15 months.Reconstituted – Stable for 4 hours at20-25°C.

Table 1: Substantial Equivalence Comparison

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7. 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.

8. Performance Characteristics

8.1 Performance Studies

Stability Studies 8.1.1

Stability studies were conducted to support the shelf life of unopened and opened ADVIA Centaur CpS 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 CpS MCM Instructions for Use.

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

Real Time/Shelf Life (unopened) Stability
On-Board Stability .

Real time shelf-life studies (unopened): Test CpS MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 3 months, 9 months, 12 months, and 13 months. At each time point 3 replicates were run for each MCM level. 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 13 month time point, which supports a shelf-life claim of 12 months. Unopened storage shelf-life is indicated by the expiration date on the MCM vial label.

On-board Stability: Pooled aliquots of test CpS 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. At each time point 3 replicates were run for each MCM level.

Stability Acceptance Criteria

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

Real Time/Shelf life (Unopened): The dose recovery for MCM1 must be ● < 0.15 ng/mL dose: MCM2, the % dose recovery must be within 85 to 115%; MCM3-10, the % dose recovery must be within 88 to 112% calculated back to Day 0 and/or no adverse trends.

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On-Board: The dose recovery for MCM1 must be ≤ 0.15 ng/mL dose; MCM2, . the % dose recovery must be within 85 to 115%; MCM3-10, the % dose recovery must be within 88 to 112% calculated to T=0.

8.1.2 Value Assignment

The ADVIA Centaur CpS MCMs are value assigned using assigned reference standards. The assigned reference standards are prepared using CpS stock and are standardized against World Health Organization (WHO) IS 84/510 reference material. The MCMs are manufactured using qualified materials and measurement procedures.

MCM1-10 are run in 3 replicates across two ADVIA Centaur instruments using two reagent kit lots, run twice on each instrument for a total of 24 replicates per MCM level. MCM9 is run diluted 1:2 using the MCM1 level. The average MCMs dose values are generated using the master curve standard calibration. The MCM10 dose value is calculated by multiplying the MCM9 dose value by 2. Three levels of commercially available controls and two levels in-house controls are used to verify acceptable value assignment runs and validate the results. The two in-house controls are diluted using diluents buffer to satisfy a 0.40-0.60 ng/mL and 12.0-18.0 ng/mL concentration of C-peptide respectively. The average dose for each in-house and commercial control from the value assignment runs are expected to be within +/-10% of the assigned targets and the ratio of in-house control RLUs to the Standard 1 RLUs (reaction counts) must be within 25-65. The average dose values obtained are the new MCM dose values (target). The new MCM doses must fall within the target range for each MCM level as outlined in Table 1.

MCMLevel	Target(ng/mL)	Target Range(ng/mL)
MCM1	0.00	< 0.06
MCM2	0.14	0.10–0.18
MCM3	0.25	0.20–0.30
MCM4	0.55	0.40–0.70
MCM5	1.05	0.80–1.30
MCM6	2.05	1.70–2.40
MCM7	4.00	3.50–4.50
MCM8	8.00	7.00–9.00
MCM9	16.0	14.0–18.0
MCM10	32.5	30.0–35.0

Table 1: CpS MCM Target and Target Ranges

8.1.3 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.

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MCM Level	% Interval
MCM1	N/A
MCM2	30
MCM3	30
MCM4	30
MCM5	30
MCM6	25
MCM7	25
MCM8	25
MCM9	25
MCM10	25

The target for MCM1 is assigned a 0.0 dose. There is no statistical method used to assign the 0.0 dose. The MCM1 range is always assigned as "< " less than 0.09 ng/mL. MCM1 is analyte-free citric acid buffer comprising of only the matrix and preservatives

If the above % interval creates an overlapping range for any two MCM levels, the ranges are adjusted using the following process: The low range value for the next MCM level is set at +0.01 of the high range value of the previous MCM level.

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

MCM level	Target (ng/mL)	Assigned Target (ng/mL)	Assigned Range (ng/mL)
MCM1	0.00	0.00	< 0.09
MCM2	0.14	0.17	0.12-0.22
MCM3	0.25	0.26	0.23-0.34
MCM4	0.55	0.61	0.43-0.79
MCM5	1.05	1.07	0.80-1.39
MCM6	2.05	2.28	1.71-2.85
MCM7	4.00	4.40	3.30-5.50
MCM8	8.00	8.91	6.68-11.1
MCM9	16.0	16.6	12.5-20.8
MCM10	32.5	33.2	24.9-41.5
Assay Range	0.05-30 ng/mL

Table 2: Lot-specific CpS MCM Target and Assigned Target and Range

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9.2.4 Traceability

The ADVIA Centaur CpS assay is traceable to World Health Organization (WHO) IS 84/510 reference material. Assigned values for master curve standards. calibrators, and MCMs are traceable to this standardization. The CpS 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 CpS 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 C-Peptide CalCheck 5. Based on the testing completed and the comparisons with the predicate device, the ADVIA Centaur CpS MCM does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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510(k) Summary

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: K142864

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:	October 23, 2014

1. Device Name Proprietary Name: Measurand: Type of Test:
  Regulation Section: Classification: Products Code:

Panel:

1. Predicate Device Name Predicate 510(k) No:
1. Device Description:

5. Intended Use: Indication for Use:

ADVIA Centaur® IRI Master Curve Material

Quality Control materials for ADVIA Centaur IRI assay Master Curve Material (MCM) for ADVIA Centaur IRI assay

21 CFR 862.1660, Ouality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)

Elecsys Insulin CalCheck 5 K101075

See Indications for Use Statement below: The ADVIA Centaur® Insulin (IRI) Master Curve Material is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Insulin assay.

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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.
6. Technological Characteristicsand Substantial EquivalenceComparison with Predicate:	A comparison of the device features, intended use, and otherinformation demonstrates that the ADVIA Centaur IRI MCMis substantially equivalent to the predicate device assummarized in Table 1.

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SIMILARITIES
	Candidate Device	Predicate Device
Item	ADVIA Centaur IRI MCM	Elecsys Insulin CalCheck 5
IntendedUse	The ADVIA Centaur Insulin (IRI) MCM is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur Insulin assay.	The Elecsys Insulin CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established by the Elecsys Insulin reagent on the indicated Elecsys and cobas e immunoassay analyzers.
Analyte	Insulin	Same
Use	Multiple Use	Same
Storage	2-8°C	Same
DIFFERENCES
Matrix	Buffered saline with casein, potassiumthiocyanate and azide	Bovine Serum matrix
Form	Liquid	Lyophilized
Levels	10	5
Stability	Unopened – Stable when storedunopened at 2-8°C for 11 months.Opened - Stable on-board for 8 hours.	Unopened - Stable at 2-8°C for18 months.Opened (Reconstituted) - Stable for4 hours at 20-25°C.

Table 1: Substantial Equivalence Comparison

7. Test Principle

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8. Performance Characteristics

8.1 Performance Studies:

Stability Studies 8.1.1

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

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

Real Time/Shelf Life (unopened) Stability ●
. On-Board Stability

Real time shelf-life studies (unopened): Test IRI MCMs were stored unopened at 2-8°C and tested at T=0 and at the following time points: 3 months, 7 months, 9 months and 12 months. At each time point 3 replicates were run for each MCM level. 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 12 month time point. which supports a shelf-life claim of 11 months. Unopened storage shelf-life is indicated by the expiration date on the vial label.

On-board Stability: Pooled aliquots of test IRI MCMs in sample cups were stored on the ADVIA Centaur system and measured at time point T= 0. 2. 4. 6. 8. and 9 hours. Acceptance criteria for the on-board stability study were met up to 9 hours, which supports the on-board stability claim for 8 hours. At each time point 3 replicates were run for each MCM level.

Stability Acceptance Criteria

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

. Real Time/Shelf life (Unopened): The dose recovery for MCM1 must be ≤ 1.5 mU/L dose; MCM2, the % dose recovery must be within 85 to 115%; MCM3-10, the % dose recovery must be within 88 to 112% calculated to Day 0 and/or no adverse trends.
On-Board: The dose recovery for MCM1 must be ≤ 1.5 mU/L dose; MCM2, the % dose recovery must be within 85 to 115%; MCM3-10, the % dose recovery must be within 88% to 112% calculated to Time=0.

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8.1.2 Value Assignment

The ADVIA Centaur IRI MCMs are value assigned using assigned reference standards. The assigned reference standards are prepared using IRI stock and are standardized against World Health Organization (WHO) 1st IRP 66/304 reference material. The MCMs are manufactured using qualified materials and measurement procedures.

MCM1-10 are run in replicates of three across two ADVIA Centaur instruments using two reagent kit lots, run twice on each instrument for a total of 24 replicates per MCM level. MCM10 is also run diluted 1:2 using the MCM1 level as diluent. The average MCMs dose values are generated using the master curve standard calibration. Two lots of commercially available controls (3 levels) are used to verify acceptable value assignment runs and validate the results. The average dose for each commercial control from the value assignment runs are expected to be within +/- 10% of the assigned targets and the coefficient of variation value from each commercial control is to be within 10%. The average dose values obtained are the new MCM dose values (target). The MCM10 dose value (target) is the average dose value of the neat and diluted samples. The new MCM doses must fall within the target range for each MCM level as outlined in Table 1.

MCM	Target	Target Range
Level	(mU/L)	(mU/L)
MCM1	0.00	< 0.50
MCM2	2.50	2.00-3.00
MCM3	4.50	4.00-5.00
MCM4	10.0	9.00-11.0
MCM5	20.0	18.0-22.0
MCM6	39.0	35.0-43.0
MCM7	79.0	71.0-87.0
MCM8	158	142-173
MCM9	225	200-250
MCM10	330	300-360

Table 1: Insulin MCM Target and Target Ranges

The target for MCM1 is assigned a 0.0 dose. There is no statistical method used to assign the 0.0 dose. The MCM1 range is always assigned as "<" less than 2.05 mU/L. MCM1 is analyte-free buffered saline comprising of only the matrix and preservatives.

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8.1.3 Expected Values

MCM Level	% Interval
MCM1	N/A
MCM2	20
MCM3	20
MCM4	20
MCM5	20
MCM6	20
MCM7	20
MCM8	18
MCM915
MCM10	12

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

MCM Level	Target Values(mU/L)	Assigned Values(mU/L)	Assigned Range(mU/L)
MCM1	0.00	0.00	< 2.05
MCM2	2.50	2.52	2.06-3.02
MCM3	4.50	4.73	3.78–5.68
MCM4	10.0	10.0	8.00-12.0
MCM5	20.0	18.9	15.1-22.7
MCM6	39.0	38.3	30.6-46.0
MCM7	79.0	72.3	57.8-86.8
MCM8	158	168	138–198
MCM9	225	234	199–269
MCM10	330	322	283–361
Assay Range	0.50–300 mU/L

Table 2: Lot-specific IRI MCM Target and Assigned Values

9.2.4 Traceability

The ADVIA Centaur Insulin assay is standardized against World Health Organization (WHO) 1st IRP 66/304. Assigned values for master curve standards, calibrators and MCMs are traceable to this standardization. The IRI MCMs are manufactured using qualified materials and measurement procedures.

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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 IRI 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 Insulin CalCheck 5. Based on the testing completed and the comparisons with predicate device, the ADVIA Centaur IRI 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.