IMMULITE 2000; HCG CALIBRATION VERIFICATION MATERIAL, INSULIN CALIBRATION VERIFICATION MATERIAL, PYRILINKS-D CALIBRATION by Siemens Healthcare Diagnostics Inc.

The IMMULITE® HCG Calibration Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE HCG assay on the IMMULITE 2000 systems.

The IMMULITE® Insulin Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Insulin assay on the IMMULITE 2000 systems.

The IMMULITE® Pyrilinks-D Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Pyrilinks-D assay on the IMMULITE 2000 systems.

The IMMULITE® Homocysteine Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Homocysteine assay on the IMMULITE 2000 systems.

The IMMULITE® Growth Hormone Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Growth Hormone assay on the IMMULITE 2000 systems.

Device Description

IMMULITE® 2000 HCG Calibration Verification Material: The Calibration Verification Material (CVM) contains One set of four vials each 3mL. CVM1 contains HCG-free human serum with preservatives. CVM2. CVM3 and CVM4 contain HCG added to HCG-free human serum respectively, with preservatives.

IMMULITE® 2000 Insulin Calibration Verification Material: The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVMI contains an equine serum matrix with preservatives. CVM2, CVM3 and CVM4 contain various levels of insulin in an equine serum matrix with preservatives.

IMMULITE® 2000 Pyrilinks-D Calibration Verification Material: The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM1 contains a phosphoric acid and sodium chloride matrix. CVM2, CVM3 and CVM4 contain various levels of H-Deoxypyridinoline in a phosphoric acid and sodium chloride matrix.

IMMULITE® 2000 Homocysteine Calibration Verification Material: The Calibration Verification Material (CVM) contains one set of four vials, 2mL each. CVM 1 contains a bovine protein/buffer matrix with preservatives. CVM2, CVM3 and CVM4, contain various levels of s-adenosyl-L-homocysteine in a bovine protein/buffer matrix with preservatives.

IMMULITE® 2000 Growth Hormone Calibration Verification Material: The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM 1 contains an equine serum matrix with preservatives. CVM2, CVM3 and CVM4 contain various levels of human growth hormone in equine serum matrix with preservatives.

AI/ML Overview

The provided text describes the acceptance criteria and performance data for several Calibration Verification Materials (CVMs) for the IMMULITE 2000 system, specifically for HCG, Insulin, Pyrilinks-D, Homocysteine, and Growth Hormone assays. The information is presented in sections relating to each CVM. I will extract the requested information for each CVM separately.

IMMULITE® 2000 HCG Calibration Verification Material

1. A table of acceptance criteria and the reported device performance:

CVM Level	Assigned Dose (mIU/mL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (mIU/mL)	Reported Performance (Guideline Range based on Target Mean & ±2SD) (mIU/mL)
LCGCVM1	0.00	N/A	<0.40	≤0.40
LCGCVM2	9.35	±12%	8.23 - 10.47	4.59 - 6.21 (Note: Target Mean for CVM2 is 5.4, not 9.35 as in accepted criteria table)
LCGCVM3	654	±8%	601.68 - 706.32	588 - 734 (Note: Target Mean for CVM3 is 661, not 654)
LCGCVM4	5327	±23%	4101.79 - 6552.21	3823 - 6107 (Note: Target Mean for CVM4 is 4965, not 5327)
Assay Range	1 - 5000 mIU/mL			1 - 5000 mIU/mL

Review Limits (Part 2 criteria for all levels): Controls are within 2SD of the control target value when generated from the stability calibrator curve.

The reported performance (Guideline ±2SD Range) in section 7.4 ("Expected Values/Reference Range") is related to the "Target Mean" which differs from the "Assigned Dose" in the acceptance criteria table (Table 3), specifically for CVM levels 2, 3, and 4. This suggests a potential discrepancy between the defined acceptance criteria values and the target values used to generate the performance data.

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

Sample size: Not explicitly stated as a "test set" in the context of device performance directly against acceptance criteria. However, for "Value Assignment" and "Expected Values/Reference Range":
- Six levels of commercially available controls and 30 pregnancy samples were used to validate calibrator/CVM value assignments.
- Each CVM level was tested for a total of 15 replicates (5 runs and 3 replicates per run) for establishing expected values/reference range.
Data provenance: Not specified (e.g., country of origin). The study is non-clinical performance testing.

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

Not applicable in this context. The "ground truth" for the CVMs is based on assigned reference calibrators traceable to WHO 3rd IS (75/537) and internal manufacturing/measurement procedures.

4. Adjudication method for the test set:

Not applicable. The stability acceptance criteria include a two-part review process:
- Part 1: Dose value within a specified percentage difference of the assigned dose.
- Part 2 (if Part 1 fails): Dose value of controls must be within 2SD of the control target value when generated from the stability calibrator curve.

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 a non-clinical performance study for in vitro diagnostic calibration verification materials, not a study involving human readers or AI assistance.

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

Not applicable. This is a stability and value assignment study for chemical calibrators.

7. The type of ground truth used:

Traceability: The IMMULITE HCG CVMs are traceable to WHO 3rd IS (75/537).
Value Assignment: CVMs are value assigned using assigned reference calibrators prepared using HCG antigen spiked in a human serum matrix with preservatives, traceable to WHO 3rd IS (75/537).

8. The sample size for the training set:

Not applicable. This is not a machine learning model, so there isn't a "training set" in that sense. However, for developing the values, 15 replicates across 5 systems and 3 different reagent kit lots were used to generate CVM values, and 6 levels of commercially available controls and 30 pregnancy samples were used to validate value assignments.

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

Not applicable. The "ground truth" (assigned values) is established through traceability to international standards (WHO 3rd IS (75/537)) and internal gravimetric preparation and measurement procedures.

IMMULITE® 2000 Insulin Calibration Verification Material

1. A table of acceptance criteria and the reported device performance:

CVM Level	Assigned Dose (µIU/mL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (µIU/mL)	Reported Performance (Guideline Range based on Target Mean & ±2SD) (µIU/mL)
LINCVM1	0.00	N/A	<2.00	≤2.00
LINCVM2	7.00	±12%	6.16 - 7.84	5.95 - 8.05
LINCVM3	26.1	±10%	23.49 - 28.71	23.5 - 28.7
LINCVM4	418	±13%	363.66 - 472.34	Not directly reported (Target Mean 418, but a diluted sample 314* is reported)
CVM4*	314	N/A (Diluted)	N/A	273 - 355 (for diluted CVM4)
Assay Range	0.2 - 300 µIU/mL			0.2 - 300 µIU/mL

Review Limits (Part 2 criteria for all levels): Controls are within 2SD of the control target value when generated from the stability calibrator curve.

The reported performance for CVM4 in the "Expected Values/Reference Range" section is for a diluted sample (75% CVM4 + 25% CVM1), not the raw "Assigned Dose" of 418 µIU/mL. This note indicates that CVM4 requires dilution for testing.

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

Sample size: Not explicitly stated as a "test set" in the context of device performance directly against acceptance criteria. However, for "Value Assignment" and "Expected Values/Reference Range":
- Two levels of commercially available controls and 30 patient samples (20 normal, 10 spiked) were used to validate calibrator/CVM value assignments.
- Each CVM level was tested for a total of 26 replicates (9 runs and 2 or 3 replicates per run) for establishing expected values/reference range.
Data provenance: Not specified (e.g., country of origin). The study is non-clinical performance testing.

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

Not applicable. The "ground truth" for the CVMs is based on assigned reference calibrators traceable to WHO NIBSC 1st IRP (66/304) and internal manufacturing/measurement procedures.

4. Adjudication method for the test set:

Not applicable. The stability acceptance criteria include a two-part review process:
- Part 1: Dose value within a specified percentage difference of the assigned dose.
- Part 2 (if Part 1 fails): Dose value of controls must be within 2SD of the control target value when generated from the stability calibrator curve.

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 a non-clinical performance study for in vitro diagnostic calibration verification materials, not a study involving human readers or AI assistance.

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

Not applicable. This is a stability and value assignment study for chemical calibrators.

7. The type of ground truth used:

Traceability: The IMMULITE Insulin CVMs are traceable to WHO NIBSC 1st IRP (66/304).
Value Assignment: CVMs are value assigned using assigned reference calibrators prepared using recombinant human Insulin antigen spiked into horse Serum with preservatives.

8. The sample size for the training set:

Not applicable. This is not a machine learning model. For developing the values, 26 replicates across 7 systems and 5 different reagent kit lots were used to generate CVM values, and 2 levels of commercially available controls and 30 patient samples were used to validate value assignments.

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

Not applicable. The "ground truth" (assigned values) is established through traceability to international standards (WHO NIBSC 1st IRP (66/304)) and internal gravimetric preparation and measurement procedures.

IMMULITE® 2000 Pyrilinks-D Calibration Verification Material

1. A table of acceptance criteria and the reported device performance:

CVM Level	Assigned Dose (nmol/L)	Guideline Criteria % difference to assigned dose	Acceptable dose range (nmol/L)	Reported Performance (Guideline Range based on Target Mean & ±2SD) (nmol/L)
LPDCVM1	0.00	N/A	<7.00	≤7.00
LPDCVM2	18.30	±10%	16.47 - 20.13	16.3 - 22.8 (Note: Target Mean for CVM2 is 16.3, not 18.30)
LPDCVM3	49.00	±10%	44.10 - 53.90	49.2 - 60.0 (Note: Target Mean for CVM3 is 49.2, not 49.00)
LPDCVM4	302.00	±10%	271.80 - 332.20	301 - 331 (Note: Target Mean for CVM4 is 301, not 302.00)
Assay Range	7 - 300 nmol/L			7 - 300 nmol/L

Review Limits (Part 2 criteria for all levels): Controls are within 2SD of the control target value when generated from the stability calibrator curve.

The reported performance (Guideline ±2SD Range) in section 7.4 ("Expected Values/Reference Range") shows slightly different "Target Mean" values compared to the "Assigned Dose" in the acceptance criteria table (Table 3) for CVM levels 2, 3, and 4.

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

Sample size: Not explicitly stated as a "test set" in the context of device performance directly against acceptance criteria. However, for "Value Assignment" and "Expected Values/Reference Range":
- Two levels of commercially available controls and 30 patient female urine samples were used to validate calibrator/CVM value assignments.
- Each CVM level was tested for a total of 15 replicates (5 runs and 3 replicates per run) for establishing expected values/reference range.
Data provenance: Not specified (e.g., country of origin). The study is non-clinical performance testing.

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

Not applicable. The "ground truth" for the CVMs is based on internal gravimetrically prepared material and manufacturing/measurement procedures.

4. Adjudication method for the test set:

Not applicable. The stability acceptance criteria include a two-part review process:
- Part 1: Dose value within a specified percentage difference of the assigned dose.
- Part 2 (if Part 1 fails): Dose value of controls must be within 2SD of the control target value when generated from the stability calibrator curve.

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 a non-clinical performance study for in vitro diagnostic calibration verification materials, not a study involving human readers or AI assistance.

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

Not applicable. This is a stability and value assignment study for chemical calibrators.

7. The type of ground truth used:

Traceability: The IMMULITE Pyrilinks-D CVMs are traceable to internal material which has been gravimetrically prepared.
Value Assignment: CVMs are value assigned using assigned reference calibrators prepared using Hydrolysed Deoxypyridiniline antigen spiked in a phosphoric acid and sodium chloride matrix in deionised water.

8. The sample size for the training set:

Not applicable. This is not a machine learning model. For developing the values, 15 replicates across 4 systems and 3 different reagent kit lots were used to generate CVM values, and 2 levels of commercially available controls and 30 patient female urine samples were used to validate value assignments.

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

Not applicable. The "ground truth" (assigned values) is established through traceability to internal gravimetrically prepared material and internal manufacturing/measurement procedures.

IMMULITE® 2000 Homocysteine Calibration Verification Material

1. A table of acceptance criteria and the reported device performance:

CVM Level	Assigned Dose (µmol/L)	Guideline Criteria % difference to assigned dose	Acceptable dose range (µmol/L)	Reported Performance (Guideline Range based on Target Mean & ±2SD) (µmol/L)
LHOCVM1	0.00	N/A	<2.0	≤2.0
LHOCVM2	4.12	±15%	3.50 - 4.74	3.25 - 4.97 (Note: Target Mean for CVM2 is 4.11, not 4.12)
LHOCVM3	17.60	±10%	15.84 - 19.36	15.8 - 19.3 (Note: Target Mean for CVM3 is 17.5, not 17.60)
LHOCVM4	71.50	±10%	64.35 - 78.65	Not directly reported (Target Mean 73.0, but a diluted sample 51.1* is reported)
CVM4*	51.1	N/A (Diluted)	N/A	46.0 - 56.2 (for diluted CVM4)
Assay Range	2 - 50 µmol/L			2 - 50 µmol/L

Review Limits (Part 2 criteria for all levels): Controls are within 2SD of the control target value when generated from the stability calibrator curve.

The reported performance for CVM4 in the "Expected Values/Reference Range" section is for a diluted sample (70% CVM4 + 30% CVM1), not the raw "Assigned Dose" of 71.50 µmol/L. This note indicates that CVM4 requires dilution for testing.

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

Sample size: Not explicitly stated as a "test set" in the context of device performance directly against acceptance criteria. However, for "Value Assignment" and "Expected Values/Reference Range":
- Two levels of commercially available controls and 40 samples (30 spiked, 5 normal, 5 patient) were used to validate calibrator/CVM value assignments.
- Each CVM level was tested for a total of 27 replicates (9 runs and 3 replicates per run) for establishing expected values/reference range.
Data provenance: Not specified (e.g., country of origin). The study is non-clinical performance testing.

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

Not applicable. The "ground truth" for the CVMs is based on internal gravimetrically prepared material and manufacturing/measurement procedures.

4. Adjudication method for the test set:

Not applicable. The stability acceptance criteria include a two-part review process:
- Part 1: Dose value within a specified percentage difference of the assigned dose.
- Part 2 (if Part 1 fails): Dose value of controls must be within 2SD of the control target value when generated from the stability calibrator curve.

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 a non-clinical performance study for in vitro diagnostic calibration verification materials, not a study involving human readers or AI assistance.

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

Not applicable. This is a stability and value assignment study for chemical calibrators.

7. The type of ground truth used:

Traceability: The IMMULITE Homocysteine CVMs are traceable to internal material which has been gravimetrically prepared.
Value Assignment: CVMs are value assigned using assigned reference calibrators prepared using s-adenosyl-L-homocysteine spiked into a Bovine protein/buffer matrix, traceable to internal gravimetrically prepared material.

8. The sample size for the training set:

Not applicable. This is not a machine learning model. For developing the values, 27 replicates across 7 systems and 3 different reagent kit lots were used to generate CVM values, and 2 levels of commercially available controls and 40 samples were used to validate value assignments.

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

Not applicable. The "ground truth" (assigned values) is established through traceability to internal gravimetrically prepared material and internal manufacturing/measurement procedures.

IMMULITE® 2000 Growth Hormone Calibration Verification Material

1. A table of acceptance criteria and the reported device performance:

CVM Level	Assigned Dose (ng/mL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (ng/mL)	Reported Performance (Guideline Range based on Target Mean & ±2SD) (ng/mL)
LGRHCVMI	0.00	N/A	<0.01	≤0.01
LGRHCVM2	0.61	±12%	0.54 - 0.68	0.457 - 0.593 (Note: Target Mean for CVM2 is 0.525, not 0.61)
LGRHCVM3	9.6	±10%	8.64 - 10.56	7.38 - 9.02 (Note: Target Mean for CVM3 is 8.20, not 9.6)
LGRHCVM4	40	±12%	35.20 - 44.80	33.4 - 43.4 (Note: Target Mean for CVM4 is 38.4, not 40)
Assay Range	0.05 - 40 ng/mL			0.05 - 40 ng/mL

Review Limits (Part 2 criteria for all levels): Controls are within 2SD of the control target value when generated from the stability calibrator curve.

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

Sample size: Not explicitly stated as a "test set" in the context of device performance directly against acceptance criteria. However, for "Value Assignment" and "Expected Values/Reference Range":
- Six levels of commercially available controls and 30 patient samples (10 normal, 20 spiked) were used to validate calibrator/CVM value assignments.
- Each CVM level was tested for a total of 27 replicates (9 runs and 3 replicates per run) for establishing expected values/reference range.
Data provenance: Not specified (e.g., country of origin). The study is non-clinical performance testing.

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

Not applicable. The "ground truth" for the CVMs is based on assigned reference calibrators traceable to WHO 2nd IS (98/574) and internal manufacturing/measurement procedures.

4. Adjudication method for the test set:

Not applicable. The stability acceptance criteria include a two-part review process:
- Part 1: Dose value within a specified percentage difference of the assigned dose.
- Part 2 (if Part 1 fails): Dose value of controls must be within 2SD of the control target value when generated from the stability calibrator curve.

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 a non-clinical performance study for in vitro diagnostic calibration verification materials, not a study involving human readers or AI assistance.

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

Not applicable. This is a stability and value assignment study for chemical calibrators.

7. The type of ground truth used:

Traceability: The IMMULITE Growth Hormone CVMs are traceable to WHO 2nd IS (98/574).
Value Assignment: CVMs are value assigned using assigned reference calibrators prepared with human Growth Hormone spiked in an equine serum matrix with preservatives.

8. The sample size for the training set:

Not applicable. This is not a machine learning model. For developing the values, 27 replicates across 7 systems and 4 different reagent kit lots were used to generate CVM values, and 6 levels of commercially available controls and 30 patient samples were used to validate value assignments.

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

Not applicable. The "ground truth" (assigned values) is established through traceability to international standards (WHO 2nd IS (98/574)) and internal manufacturing/measurement procedures.

Summary

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Section 006: 510(k) Summary

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: _k133128

...

1. Submitter
  Mailing Address:

Contact Person:

Phone Number: Fax Number: E-mail Address: Date Prepared:

Device Name Proprietary Name: Measurand: Type of Test:

Regulation Section: Classification: Products Code: Panel:

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

1. Intended Use: Indication for Use:
  Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591

Asha Gartland Technical Regulatory Affairs Specialist (914)-524-3257 (914)-524-2101 asha.gartland@siemens.com October 16, 2013

OCT 22 2013

IMMULITE® 2000 HCG Calibration Verification Material Quality Control materials for IMMULITE® 2000 HCG assay Calibration Verification Material (CVM) for IMMULITE® 2000 HCG assav 21 CFR 862.1660, Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)

Elecsys HCG CalCheck 5 K092168

The Calibration Verification Material (CVM) contains One set of four vials each 3mL. CVM1 contains HCG-free human serum with preservatives. CVM2. CVM3 and CVM4 contain HCG added to HCG-free human serum respectively, with preservatives.

See Indications for Use Statement below:

The IMMULITE® HCG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE HCG assay on the IMMULITE 2000 systems.

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Special Conditions for Use Statement(s): Special Instrument Requirements:
1. Technological Characteristics and Substantial Equivalence Comparison with Predicate:

For prescription use only

IMMULITE® 2000 Systems

A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 HCG Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.

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Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate DeviceIMMULITE 2000 HCG CVM	Predicate DeviceElecsys HCG CalCheck 5
IntendedUse	The IMMULITE® HCG CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration of the IMMULITE HCG assayon the IMMULITE 2000 systems.	The Elecsys HCG CalCheck 5 is anassayed control for use in calibrationverification and for use in theverification of the assay rangeestablished by the Elecsys HCG+Breagent and Elecsys HCG STAT reagenton the indicated Elecsys and cobas eimmunoassay analyzers.
Analyte	HCG	Same
Matrix	Human Serum with preservatives	Same
Stability	Stable unopened until the expiration date	Same

	DIFFERENCES
	Candidate DeviceIMMULITE 2000 HCG CVM	Predicate DeviceElecsys HCG CalCheck 5
Form	Liquid	Lyophilized
Levels	4	5
Storage	≤20°C	2-8°C
Use	Single Use Only	Not For Single Use

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7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.

7.1 Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 HCG Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 HCG Calibration Verification Materials are stable up to 2.5 years when stored frozen at -20℃ prior to opening.

7.1.1 Stability Protocol Summary:

The CVM study protocols are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) at the time points shown in Table 2 and the dose value determined from the reference calibrator curve.

CVM Level	Time-Points (Days)
LCGCVM1	1	548	730	912
LCGCVM2	1	548	730	912
LCGCVM3	1	548	730	912
LCGCVM4	1	548	730	912

Table 2: Stability Time Points

7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE HCG Calibration Verification Material (CVM) consists of 2 parts. Part 1 consists of the Guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±12% of assigned dose for CVM level 2 and ±8% of assigned dose for CVM levels 3 and 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±12% for level 2 and ±8% for levels 3 and 4 then additional data review is conducted using part 2 criteria. The acceptance criterion is summarized in Table 3.

Table 3 Acceptance criteria for stability of IMMULITE 2000 HCG CVM

CVM Level	Assigned Dose (mIU/mL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (mIU/mL)	Review Limits
LCGCVM1	0.00	N/A	<0.40	Controls are
LCGCVM2	9.35	$ \pm $ 12	8.23 - 10.47	within 2SD
LCGCVM3	654	$ \pm $ 8	601.68 - 706.32	of target on
LCGCVM4	5327	$ \pm $ 23	4101.79-6552.21	each curve

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7.2 Traceability:

The IMMULITE HCG CVMs are traceable to WHO 3rd IS (75/537) and are manufactured using qualified materials and measurement procedures.

7.3 Value Assignment:

HCG CVMs are 4 level materials which are a subset of 12 level HCG calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of HCG reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using HCG antigen spiked in a human serum matrix with preservatives and are traceable to WHO 3rd IS (75/537). Six levels of commercially available controls, and 30 pregnancy samples were used to validate calibrator/CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 15 replicates in total comprised of 5 runs and 3 replicates per run on 5 systems and 3 different reagent kit lots. The CVMs' dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges.

7.4 Expected Values/Reference Range:

Each CVM level was tested for a total of 15 replicates; 5 runs and 3 replicates per run. 3 different reagent kit lots and 5 different instruments were used to gain 15 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific package insert. The expected assay range is 1 - 5000 mIU/mL. The target values in Table 4 can be considered as guidelines.

Analytetarget levels	CVM Level	Target Mean(mIU/mL)	StandardDeviation(SD)	Guideline ±2SD Range(mIU/mL)
	CVM1	0.00	-	0.00 $\leq$ 0.40
	CVM2	5:4	0.405	4.59	6.21
	CVM3	661	36.5	588	734
	CVM4	4965	571	3823	6107
Assay Range	1 - 5000 mIU/mL

Table 4: Target Values

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Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, total precision tabulated in the respective assay instructions for use may be considered as one factor when establishing local, acceptable ranges. The values provided above may be considered as guidelines. Value assignment is lot specific.

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents 0
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic . Calibrators
Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control o Material

Proposed Labeling:

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

8. Conclusion:

The IMMULITE® 2000 HCG Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Elecsys HCG CalCheck 5. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 HCG Calibration Verification Material 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: K133128

1. Submitter
Mailing Address:	Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591
Contact Person:	Asha Gartland
	Technical Regulatory Affairs Specialist
Phone Number:	(914)-524-3257
Fax Number:	(914)-524-2101
E-mail Address:	asha.gartland@siemens.com
Date Prepared:	October 16, 2013
2. Device Name
Proprietary Name:	IMMULITE® 2000 Insulin Calibration Verification Material
Measurand:	Quality Control materials for IMMULITE® 2000 Insulin assay
	Calibration Verification Material (CVM) for IMMULITE® 2000
Type of Test:	Insulin 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 Insulin CalCheck 5
Predicate 510(k) No:	K101075
4. Device Description:	The Calibration Verification Material (CVM) contains one set of fourvials, 2 mL each. CVMI contains an equine serum matrix withpreservatives. CVM2, CVM3 and CVM4 contain various levels ofinsulin in an equine serum matrix with preservatives.
5. Intended Use:
Indication for Use:	See Indications for Use Statement belowThe IMMULITE® Insulin Calibration Verification Material (CVM)is for in vitro diagnostic use in the verification of calibration of theIMMULITE Insulin assay on the IMMULITE 2000 systems

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Special Conditions forUse Statement(s):Special InstrumentRequirements:	For prescription use onlyIMMULITE® 2000 Systems
6. TechnologicalCharacteristics andSubstantial EquivalenceComparison with Predicate:	A comparison of the device features, intended use, and otherinformation demonstrates that the IMMULITE® 2000 InsulinCalibration Verification Material (CVM) is substantially equivalent tothe predicate device as summarized in Table 1.

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE 2000 Insulin CVM	Elecsys Insulin CalCheck 5
Intended Use	The IMMULITE® Insulin CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration of the IMMULITE Insulinassay on the IMMULITE 2000 systems	The Elecsys Insulin CalCheck 5 is anassayed control for use in calibrationverification and for use in theverification of the assay rangeestablished by the Elecsys Insulinreagent on the indicated Elecsys andcobas e immunoassay analyzers.
Analyte	Insulin	Same
Form	Lyophilized	Same
Stability	Stable unopened until the expiration date	Same

	DIFFERENCES
	Candidate DeviceIMMULITE 2000 Insulin CVM	Predicate DeviceElecsys Insulin CalCheck 5
Matrix	Equine serum with preservatives	Bovine serum with preservatives
Storage	≤20°C	2-8 °C
Levels	4	5
Use	Single Use Only	Not For Single Use

{8}------------------------------------------------

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use. The following tests were performed on the candidate device.

7.1 Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Insulin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 Calibration Verification Materials are stable up to 5 years when stored at -20℃ prior to opening.

7.1.1 Stability Protocol Summary:

CVM Level	Time-Points (Days)
LINCVMI	1	1280	1460	1825
LINCVM2	1	1280	1460	1825
LINCVM3	1	1280	1460	1825
LINCVM4	1	1280	1460	1825

Table 2: Stability Time Points

7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Insulin Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±12% of assigned dose for CVM level 2, ±10% of assigned dose for CVM levels 3 and ±13% for CVM level 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve: If the result is not within acceptable dose range of ±12% for level 2, ±10% for levels 3 and ±13% for CVM level 4 then additional data review is conducted using part 2 criteria. The acceptance criterion is summarized in Table 3.

CVM level	AssignedDose( $\mu$ IU/mL)	Guideline Criteria% difference to assigneddose	Acceptable dose range( $\mu$ IU/mL)	ReviewLimits
LINCVM1	0.00	N/A	<2.00	Controls are
LINCVM2	7.00	$\pm$ 12%	6.16 - 7.84	within 2SD
LINCVM3	26.1	$\pm$ 10%	23.49 - 28.71	of target on
LINCVM4	418	$\pm$ 13%	363.66 - 472.34	each curve

Table 3: Acceptance criteria for stability of IMMULITE 2000 Insulin CVM

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7.2 Traceability:

The IMMULITE Insulin CVMs are traceable to WHO NIBSC 1st IRP (66/304). The CVMs are manufactured using qualified materials and measurement procedures.

7.3 Value Assignment:

The Insulin CVMs are 4 level materials which are a subset of 10 level Insulin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Insulin reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using recombinant human Insulin antigen spiked into horse Serum with preservatives. Two levels of commercially available controls, and 30 patient samples (20 normal patients samples and 10 spiked samples) are used to validate calibrator/CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 26 replicates in total comprised of 9 runs and 2 or 3 replicates per run on 7 systems and 5 different reagent kit lots. The CVMs' dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges.

7.4 Expected Values/Reference Range:

Each CVM level was tested for a total of 26 replicates; 9 runs and 2 or 3 replicates per run. 5 different reagent kit lots and 7 different instruments were used to gain 26 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration Verification Material lot-specific package insert The expected assay range is 0.2 -300 µIU/mL. The target values in Table 4 can be considered as guidelines.

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CVM Level	Target Mean(µIU/mL)	StandardDeviation(SD)	Guideline ±2SDRange(µIU/mL)
CVM1	0.00	-	0.00	2.00
CVM2	7.00	0.53	5.95	8.05
CVM3	26.1	1.3	23.5	28.7
CVM4	418	-	-	-
CVM4	314 *(75% CVM4+25% CVM1)	20.5	273	355

| Assay Range | 0.2 -300 µIU/mL

Note: CVM4 requires dilution to ensure the target value is within +10% of the top of the reportable range of the assay.

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents ●
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic . Calibrators
o Guidance for Industry and FDA Staff - Assayed and Unassayed Quality Control Material

Proposed Labeling:

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

8. Conclusion:

The IMMULITE® 2000 Insulin Calibration Verification Material 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. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Insulin Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

{11}------------------------------------------------

510(k) Summary

1. Submitter Mailing Address: Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591 Contact Person: Asha Gartland Technical Regulatory Affairs Specialist Phone Number: (914)-524-3257 Fax Number: (914)-524-2101 E-mail Address: asha.gartland@siemens.com Date Prepared: October 16, 2013 IMMULITE® 2000 Pyrilinks-D Calibration Verification 2. Device Name Proprietary Name: Material Quality Control materials for IMMULITE® 2000 Pyrilinks-D Measurand: Type of Test: assav Calibration Verification Material (CVM) for IMMULITE® 2000 Pyrilinks-D assay Regulation Section: 21 CFR 862.1660, Quality Control Material Classification: Class I Reserved JJX – Single (Specified) Analyte Controls (Assayed and Products Code: Unassaved) Panel: Clinical Chemistry (75) IMMULITE® Unconjugated Estriol (uE3) Calibration 3. Predicate Device Name Verification Material (CVM) Predicate 510(k) No: K ! 1006 ! 4. Device Description: The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM1 contains a phosphoric acid and sodium chloride matrix. CVM2, CVM3 and CVM4 contain various levels of H-Deoxypyridinoline in a phosphoric acid and sodium chloride matrix. 5. Intended Use: See Indications for Use Statement below Indication for Use: The IMMULITE® Pyrilinks-D Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Pyrilinks-D assay on the IMMULITE 2000 systems

{12}------------------------------------------------

Special Conditions for Use Statement(s):	For prescription use only
Special Instrument Requirements:	IMMULITE® 2000 Systems

Technological Characteristics and Substantial Equivalence Comparison with Predicate: A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Pyrilinks-D Calibration Verification Material (CVM) is substantially equivalent to the predicate device, as summarized in Table 1.

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate DeviceIMMULITE 2000 Pyrilinks-D CVM	Predicate DeviceIMMULITE uE3 CalibrationVerification Material (CVM)
IntendedUse	The IMMULITE® Pyrilinks-DCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Pyrilinks-D assay on theIMMULITE 2000 systems.	For in vitro diagnostic use as acontrol for the calibrationverification of the IMMULITE®Unconjugated Estriol (uE3) assayson the IMMULITE/IMMULITE1000 and 2000 systems.
Form	Liquid	Same
Levels	4	Same
Stability	Stable unopened until the expirationdate	Same
Use	Single Use Only	Same
DIFFERENCES
	Candidate DeviceIMMULITE 2000 Pyrilinks-D CVM	Predicate DeviceIMMULITE uE3 CalibrationVerification Material (CVM)
Analyte	Pyrilinks-D	Unconjugated Estriol
Matrix	phosphoric acid and sodium chloride	Horse serum with preservatives
Storage	≤20°C	2-8°C

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use. The following tests were performed on the candidate device.

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7.1 Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Pyrilinks-D Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 Pyrilinks-D Calibration Verification Materials (CVMs) are stable up to5 years when stored at -20℃ prior to opening.

7.1.1 Stability Protocol Summary:

CVM Level	Time-Points (Days)
LPDCVM1	1	1280	1460	1642	1825
LPDCVM2	1	1280	1460	1642	1825
LPDCVM3	1	1280	1460	1642	1825
LPDCVM4	1	1280	1460	1642	1825

Table 2: Stability Time Points

7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Pyrilinks-D Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±10% of assigned dose. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±10% then additional data review is conducted using part 2 criteria. The acceptance criterion is summarized in Table 3.

Table 3: Acceptance criteria for stability of IMMULITE 2000 Pyrilinks-D CVM

CVM level	AssignedDose(nmol/L)	Guideline Criteria% difference to assigneddose	Acceptable dose range(nmol/L)	ReviewLimits
LPDCVM1	0.00	N/A	<7.00	Controls arewithin 2SDof target oneach curve
LPDCVM2	18.30	±10%	16.47 - 20.13
LPDCVM3	49.00	±10%	44.10 - 53.90
LPDCVM4	302.00	±10%	271.80 - 332.20

{14}------------------------------------------------

7.2 Traceability:

The IMMULITE Pyrilinks-D CVMs are traceable to internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.

7.3 Value Assignment:

Pyrilinks-D CVMs are 4 level materials which are a subset of 8 level Pvrilinks-D calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Pyrilinks-D reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using Hydrolysed Deoxypyridiniline antigen spiked in a matrix consisting of Phosphoric acid and Sodium Chloride in deionised water. Two levels of commercially available controls and 30 patient female urine samples are used to validate calibrator/CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 15 replicates in total comprised of 5 runs and 3 replicates per run on 4 systems and 3 different reagent kit lots. The CVMs' dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges.

7.4 Expected Values/Reference Range:

Each CVM level was tested for a total of 15 replicates; 5 runs and 3 replicates per run. 3 different reagent kit lots and 4 different instruments were used to gain 15 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration Verification Material lot-specific package insert. The expected assay range is 7 -300 nmol/L. The target values in Table 4 can be considered as guidelines.

Analyte targetlevels	CVM Level	Target Mean(nmol/L)	StandardDeviationSD	Guideline ±2SD Range(nmol/L)
	CVM1	0.00	-	≤7.00
	CVM2	16.3	3.255	22.8
	CVM3	49.2	5.4	60.0
	CVM4	301	15	331
Assay Range	7 - 300 nmol/L

Table 4: Target Values

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Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents .
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic . Calibrators
. Guidance for Industry and FDA Staff - Assayed and Unassayed Quality Control Material

Proposed Labeling:

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

Conclusion: 8.

The IMMULITE® 2000 Pyrilinks-D Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed IMMULITE Unconjugated Estriol (uE3) Calibration Verification Material (CVM). The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Pvrilinks-D Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

{16}------------------------------------------------

510(k) Summary

1. SubmitterMailing Address:	Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591
Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared:	Asha GartlandTechnical Regulatory Affairs Specialist(914)-524-3257(914)-524-2101asha.gartland@siemens.comOctober 16, 2013
2. Device NameProprietary Name:Measurand:Type of Test:	IMMULITE® 2000 Homocysteine Calibration VerificationMaterialQuality Control materials for IMMULITE® 2000 Homocysteine assayCalibration Verification Material (CVM) for IMMULITE® 2000Homocysteine assay
Regulation Section:Classification:Products Code:Panel:	21 CFR 862.1660, Quality Control MaterialClass I ReservedJJX - Single (Specified) Analyte Controls (Assayed and Unassayed)Clinical Chemistry (75)
3. Predicate Device NamePredicate 510(k) No:	Audit™ MicroCV™ Homocysteine Linearity SetK100715
4. Device Description:	The Calibration Verification Material (CVM) contains one set of fourvials, 2mL each. CVM 1 contains a bovine protein/buffer matrix withpreservatives. CVM2, CVM3 and CVM4, contain various levels of s-adenosyl-L-homocysteine in a bovine protein/buffer matrix withpreservatives.
5. Intended Use:Indication for Use:	See Indications for Use Statement belowThe IMMULITE® Homocysteine Calibration Verification Materia(CVM) is for in vitro diagnostic use in the verification of calibration othe IMMULITE Homocysteine assay on the IMMULITE 2000systems
Special Conditions forUse Statement(s):	For prescription use only
Special Instrument	IMMULITE® 2000 Systems
Requirements:

{17}------------------------------------------------

A comparison of the device features, intended use, and other 6. Technological Characteristics and Substantial Equivalence information demonstrates that the IMMULITE® 2000 Homocysteine Comparison with Predicate: Calibration Verification Material (CVM) is substantially equivalent to the predicate device, as summarized in Table 1.
Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate DeviceIMMULITE 2000 Homocysteine CVM	Predicate DeviceAudit® MicroCVTM HomocysteineLinearity
IntendedUse	The IMMULITE® HomocysteineCalibration Verification Material (CVM) isfor in vitro diagnostic use in theverification of calibration of theIMMULITE Homocysteine assay on theIMMULITE 2000 systems.	The Audit® MicroCVTM HomocysteineLinearity for use with SiemensCentaur® ImmunoassaySystems, is intended to simulate humanpatient serum samples for purpose ofdetermining linearity, calibrationverification and verification ofreportable range for Homocysteine.
Analyte	Homocysteine	Same
Stability	Stable unopened until the expiration date	Same
Form	Liquid	Same

DIFFERENCES
	Candidate DeviceIMMULITE 2000 Homocysteine CVM	Predicate DeviceAudit® MicroCVTM HomocysteineLinearity
Matrix	Bovine protein/buffer matrix	Human serum
levels	4	5
Storage	≤20°C	2-8°C
Use	Single Use Only	Not For Single Use

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

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.

7.1 Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Homocysteine Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 Homocysteine Calibration Verification Materials (CVMs) are stable up to 3.5 years when stored at -20°C prior to opening.

7.1.1 Stability Protocol Summary:

CVM Level
LHOCVM1	730	912	। 095	1280
LHOCVM2	730	912	। 0652	1280
LHOCVM3	730	912	। 095	1280
LHOCVM4	730	912	। 092	1280

Table 2: Stability Protocol Summary

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Homocysteine Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±15% of assigned dose for CVM level 2, ±10% of assigned dose for CVM levels 3 and 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±15% for level 2 and ±10% for levels 3 and 4 then additional data review is conducted using part 2 criteria. The acceptance criterion is summarized in Table 3.

CVM level	AssignedDose(µmol/L)	Guideline Criteria% difference to assigneddose	Acceptable dose range(µmol/L)	ReviewLimits
LHOCVM1	0.00	N/A	<2.0	Controls arewithin 2SDof target oneach curve
LHOCVM2	4.12	±15%	3.50 - 4.74
LHOCVM3	17.60	±10%	15.84 - 19.36
LHOCVM4	71.50	±10%	64.35 - 78.65

Table 3 : Acceptance criteria for stability of IMMULITE 2000 Homocysteine CVM

{19}------------------------------------------------

7.2 Traceability:

The IMMULITE Homocysteine CVMs are traceable to internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.

7.3 Value Assignment:

Homocysteine CVMs are 4 level materials which are a subset of 7 level Homocysteine calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Homocysteine reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using s-adenosyl-L-homocysteine spiked into a Bovine protein/buffer matrix and are traceable to internal material which has been gravimetrically prepared. Two levels of commercially available controls and 40 samples (30 spiked samples, 5 normal samples and 5 patient samples) are used to validate calibrator/CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run on 7 systems and 3 different reagent kit lots. The CVMs' dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges.

7.4 Expected Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run, 3 different reagent kit lots and 7 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific package insert. The expected assay range is 2 -50 umol/L. The target values in Table 4 can be considered as guidelines.

{20}------------------------------------------------

Analyte targetlevels	CVM Levels	Target Mean(µmol/L)	StandardDeviation(SD)	Guideline ±2SDRange(µmol/L)
	CVM1	0.00	-	0.00	≤2.0
	CVM2	4.11	0.43	3.25	4.97
	CVM3	17.5	0.875	15.8	19.3
	CVM4	73.0	-	-	-
		51.1*(70% CVM4 +30% CVM1)	2.55	46.0	56.2
Assay Range	2-50 µmol/L

Table 4: Target Values

Assay Range 2 -50 μmol/L

Note: CVM4 requires dilution to ensure the target value is within +10% of the top of the reportable range of the assay.

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents ●
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic . Calibrators
Guidance for Industry and FDA Staff Assayed and Unassayed Ouality Control . Material

Proposed Labeling:

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

8. Conclusion:

The IMMULITE® 2000 Homocysteine Calibration Verification Material (CVM) is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Audit® MicroCVTM Homocysteine Linearity for use with Siemens Centaur® Immunoassay Systems. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness.

{21}------------------------------------------------

Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Homocysteine Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

{22}------------------------------------------------

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: K133128

1. Submitter Mailing Address:
  Contact Person:

Phone Number: Fax Number: E-mail Address: Date Prepared:

1. Device Name Proprietary Name: Measurand:
  Type of Test:

Regulation Section: Classification: Products Code: Panel:

Predicate Device Name

Predicate 510(k) No:

Device Description:

1. Intended Use: Indication for Use:
  Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591

Asha Gartland Technical Regulatory Affairs Specialist (914)-524-3257 (914)-524-2101 asha.gartland@siemens.com October 16, 2013

IMMULITE® 2000 Growth Hormone Calibration Verification Material

Quality Control materials for IMMULITE® 2000 Growth Hormone assav Calibration Verification Material (CVM) for IMMULITE® 2000 Growth Hormone assay

21 CFR 862.1660, Quality Control Material Class I Reserved

JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)

IMMULITE® Unconjugated Estriol (uE3) Calibration Verification Material (CVM) K110061

The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM 1 contains an equine serum matrix with preservatives. CVM2, CVM3 and CVM4 contain various levels of human growth hormone in equine serum matrix with preservatives.

See Indications for Use Statement below The IMMULITE® Growth Hormone Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Growth Hormone assay on the IMMULITE 2000 systems.

{23}------------------------------------------------

Special Conditions for Use Statement(s): Special Instrument Requirements:

1. Technological Characteristics and Substantial Equivalence Comparison with Predicate:
  For prescription use only

IMMULITE® 2000 Systems

A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Growth Hormone Calibration Verification Material (CVM) is substantially equivalent to the predicate device, as summarized in Table 1.

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate DeviceIMMULITE 2000 Growth Hormone CVM	Predicate DeviceIMMULITE uE3CalibrationVerification Material (CVM)
IntendedUse	The IMMULITE® Growth HormoneCalibration Verification Material (CVM) isfor in vitro diagnostic use in the verificationof calibration of the IMMULITE GrowthHormone assay on the IMMULITE 2000systems.	For in vitro diagnostic use as acontrol for the calibration verificationof the IMMULITE® UnconjugatedEstriol (uE3) assays on theIMMULITE/IMMULITE 1000 and2000 systems.
Matrix	Equine serum with preservatives	Same
Levels	4	Same
Stability	Stable unopened until the expirationdate on the vial	Same
Storage	2-8°C	Same
Use	Single Use Only	Same

DIFFERENCES
	Candidate DeviceIMMULITE 2000 Growth Hormone CVM	Predicate DeviceIMMULITE uE3 CalibrationVerification Material (CVM)
Analyte	Growth Hormone	Unconjugated Estriol
Form	Lyophilized	Liquid

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

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.

7.1 Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Growth Hormone Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The IMMULITE® 2000 Growth Hormone Calibration Verification Materials (CVMs) are stable up to 6 years when stored at 2-8°C prior to opening.

7.1.1 Stability Protocol Summary:

CVM Level	Time-Points (Days)
LGRHCVM1	1	1280	1642	2190
LGRHCVM2	1	1280	1642	2190
LGRHCVM3	1	1280	1642	2190
LGRHCVM4	1	1280	1642	2190

Table 2: Stability Protocol Summary

7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Growth Hormone Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±12% of assigned dose for CVM levels 2 and 4, ±10% of assigned dose for CVM level 3. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±12% for levels 2 and 4, ±10% for levels 3 then additional data review is conducted using part 2 of the criteria. The acceptance criterion is summarized in Table 3.

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CVM level	AssignedDose(ng/mL)	Guideline Criteria% difference to assigneddose	Acceptable dose range(ng/mL)	ReviewLimits
LGRHCVMI	0.00	N/A	<0.01	Controls are
LGRHCVM2	0.61	±12%	0.54 - 0.68	within 2SD
LGRHCVM3	9.6	±10%	8.64 - 10.56	of target on
LGRHCVM4	40	±12%	35.20 - 44.80	each curve

Table 3: Acceptance criteria for stability of IMMULITE 2000 Growth Hormone CVM

7.2 Traceability:

The IMMULITE Growth Hormone CVMs are traceable to WHO 2nd IS (98/574). The CVMs are manufactured using qualified materials and measurement procedures.

7.3 Value Assignment:

Growth Hormone CVMs are 4 level materials which are a subset of 9 level Growth Hormone calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Growth Hormone reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared with human Growth Hormone spiked in an equine serum matrix with preservatives. Six levels of commercially available controls and 30 patient samples (10 normal patient samples and 20 spiked samples) are used to validate calibrator/CV.M value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run on 7 systems and 4 different reagent kit lots. The CVMs' dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges

7.4 Expected Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run, 4 different reagent kit lots and 7 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific package insert. The expected assay range is 0.05 - 40 ng/mL. The target values in Table 4 can be considered as guidelines.

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Analyte targetlevels	CVM Levels	Target Mean(ng/mL)	StandardDeviation(SD)	Guideline ±2SD Range(ng/mL)
	CVM1	0.00	-	0.00≤0.01
	CVM2	0.525	0.034	0.4570.593
	CVM3	8.20	0.41	7.389.02
	CVM4	38.4	2.5	33.443.4
Assay Range	0.05 - 40 ng/mL

Table 4: Target Values
-------------------------	--

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents �
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic o Calibrators
. Guidance for Industry and FDA Staff - Assayed and Unassayed Quality Control Material

Proposed Labeling:

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

8. Conclusion:

The IMMULITE® 2000 Growth Hormone Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed IMMULITE Unconjugated Estriol (uE3) Calibration Verification Material (CVM). The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Growth Hormone Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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Image /page/27/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES". The text is in all caps and is in a bold, sans-serif font. The text is centered on the page and is the only text in the image. There is a logo to the left of the text.

Public Health Service

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

October 22, 2013

SIEMENS HEALTHCARE DIAGNOSTICS INC. c/o Asha Gartland 511 Benedict Ave TARRYTOWN NY 10591

Re: K133128

Trade/Device Name: IMMULITE® 2000 HCG Calibration Verification Material IMMULITE® 2000 Insulin Calibration Verification Material IMMULITE® 2000 Pyrilinks-D Calibration Verification Material IMMULITE® 2000Homocysteine Calibration Verification Material IMMULITE® 2000 Growth Hormone Calibration Verification Material Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed)

Regulatory Class: I, reserved Product Code: JJX Dated: September 27, 2013 Received: September 30, 2013

Dear Asha Gartland:

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 misoranding 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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Page 2-Asha Gartland

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 regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance 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" (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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours.

Carol C. Benson -S and

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

510fk) Number (if known): K133128

Device Name:

IMMULITE® 2000 HCG Calibration Verification Material IMMULITE® 2000 Insulin Calibration Verification Material IMMULITE® 2000 Pyrilinks-D Calibration Verification Material IMMULITE® 2000 Homocysteine Calibration Verification Material IMMULITE® 2000 Growth Hormone Calibration Verification Material

Indications for Use:

The IMMULITE® HCG Calibration Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE HCG assay on the IMMULITE 2000 systems.

The IMMULITE® Insulin Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Insulin assay on the IMMULITE 2000 systems.

The IMMULITE® Pyrilinks-D Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Pyrilinks-D assay on the IMMULITE 2000 systems.

The IMMULITE® Homocysteine Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Homocysteine assay on the IMMULITE 2000 systems.

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Yung W. Chan -S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health 510(k) K133128

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.