IMMULITE: 2000 FREE T4 CALIBRATION VERIFICATION MATERIAL, 2000 IGF-I CALIBRATION VERIFICATION MATERIAL, 2000 PROLACTIN C by Siemens Healthcare Diagnostics Inc.

The IMMULITE® Free T4 Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Free T4 assay on the IMMULITE 2000 systems.

The IMMULITE® IGF-1 Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE IGF-1 assay on the IMMULITE 2000 systems.

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

Device Description

The IMMULITE® 2000 Free T4 Calibration Verification Material (CVM) contains one set of four vials each ImL. CVMIcontains a lyophilized processed human serum matrix with 1.58% sodium azide and preservative and CVM2, CVM3, and CVM4 contain various levels of lyophilized Free T4 in a processed human serum matrix with 1.58% sodium azide and preservative. CVMs are supplied frozen in a lyophilized form.

The IMMULITE® 2000 IGF-I Calibration Verification Material (CVM) contains one set of four vials, 2mL (CVM1) each. CVM1 contains a processed bovine protein/buffer matrix with preservatives. CVM2, CVM3, and CVM4 contain various levels of IGF-I in a processed bovine protein/buffer matrix with preservatives. The CVMs are supplied frozen in a liquid form.

IMMULITE® 2000 Prolactin Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. CVM1 contains a lyophilized equine serum/buffer matrix with preservative. CVM2, CVM3, and CVM4 contain various levels of lyophilized prolactin in an equine serum/buffer matrix with preservative CVMs are supplied frozen in a lyophilized form.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for each of the three IMMULITE® 2000 Calibration Verification Materials (CVMs) mentioned in the provided text.

IMMULITE® 2000 Free T4 Calibration Verification Material

1. Table of Acceptance Criteria and Reported Device Performance

Level	Acceptance Criteria (Dose Value)	Reported Performance (Guideline ±2SD Range)	Target Mean (ng/dL)	Standard Deviation (SD)
LFT4CVM1	-	≤0.3 ng/dL	0.00*	-
LFT4CVM2	Within ±10% of assigned dose	1.69 ng/dL	1.51	0.09
LFT4CVM3	Within ±10% of assigned dose	3.19 ng/dL	2.90	0.145
LFT4CVM4	Within ±15% of assigned dose	7.88 ng/dL	6.85*	0.515
Part 2	Dose value of controls within 2SD of the control target value when generated from stability calibrator curve.	-	-	-

Note: The reported performance "Guideline ±2SD Range" is derived from the established Target Mean and Standard Deviation, and suggests the expected range within which the CVMs should perform. The exact demonstration of conformity to the ±10% or ±15% acceptance criteria based on this study is not explicitly stated as a pass/fail within this summary, but the derived ranges imply performance within expected limits.

2. Sample Size and Data Provenance for Test Set

Sample Size:
- 27 replicates for each CVM level (9 runs and 3 replicates per run).
- 5 different reagent kit lots.
- 9 IMMULITE 2000 systems.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). Implied to be internal, prospective testing by the manufacturer.

3. Number of Experts and Qualifications for Ground Truth of Test Set

Not applicable for this type of device (calibration verification material). The "ground truth" refers to the assigned dose values and established statistically derived ranges.

4. Adjudication Method for Test Set

Not applicable for this type of device. The evaluation is based on quantitative measurements against predefined statistical criteria.

5. MRMC Comparative Effectiveness Study

No. This is not a comparative effectiveness study involving human readers.

6. Standalone Performance Study (Algorithm Only)

Not applicable. This is a physical calibration verification material, not an algorithm. Performance is demonstrated through stability and value assignment studies in conjunction with the IMMULITE 2000 systems.

7. Type of Ground Truth Used

Assigned Reference Calibrators: The CVMs are value assigned using assigned reference calibrators.
Internal Material Gravimetrically Prepared: The CVMs are traceable to an internal material which has been gravimetrically prepared.
Statistical Derivation: Target Mean and ± 2 Standard Deviation (SD) are used to establish Guideline Ranges.

8. Sample Size for Training Set

No explicit "training set" in the context of machine learning. The "Value Assignment" process is analogous to establishing the ground truth/reference for the CVMs. This involved:

6 levels of Total Free T4 calibrators (used internally, not commercialized).
6 levels of commercially available controls.
30 normal patient samples.

9. How Ground Truth for Training Set was Established

The ground truth (value assignment) for the CVMs was established using:

Assigned reference calibrators.
CVM dose values generated using curves from these assigned reference calibrators.
CVM values calculated from recovered values for each run on each instrument independently and then averaged across all systems.
Quality control performed by calculating recovery of patient samples, spiked patient samples, and controls using the assigned CVM values.

IMMULITE® 2000 IGF-I Calibration Verification Material

1. Table of Acceptance Criteria and Reported Device Performance

Level	Acceptance Criteria (Dose Value)	Reported Performance (Guideline ±2SD Range)	Target Mean (ng/mL)	Standard Deviation (SD)
LGFCVM1	Within ±10% of assigned dose (implied for all levels as per general criteria)	≤25.00 ng/mL	0.00	-
LGFCVM2	Within ±10% of assigned dose	29.1 ng/mL	34.7	2.8
LGFCVM3	Within ±10% of assigned dose	206 ng/mL	237	15.5
LGFCVM4	Within ±10% of assigned dose	1554 ng/mL	1727*	86.5
Part 2	Dose value of controls within 2SD of the control target value when generated from stability calibrator curve.	-	-	-

Note: The reported performance "Guideline ±2SD Range" is derived from the established Target Mean and Standard Deviation, and suggests the expected range within which the CVMs should perform. The exact demonstration of conformity to the ±10% acceptance criteria based on this study is not explicitly stated as a pass/fail within this summary, but the derived ranges imply performance within expected limits.

2. Sample Size and Data Provenance for Test Set

Sample Size:
- 27 replicates for each CVM level (9 runs and 3 replicates per run).
- 7 IMMULITE 2000 systems.
- 3 different reagent kit lots.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). Implied to be internal, prospective testing by the manufacturer.

3. Number of Experts and Qualifications for Ground Truth of Test Set

Not applicable for this type of device (calibration verification material). The "ground truth" refers to the assigned dose values and established statistically derived ranges.

4. Adjudication Method for Test Set

Not applicable for this type of device. The evaluation is based on quantitative measurements against predefined statistical criteria.

5. MRMC Comparative Effectiveness Study

No. This is not a comparative effectiveness study involving human readers.

6. Standalone Performance Study (Algorithm Only)

7. Type of Ground Truth Used

Assigned Reference Calibrators: The CVMs are value assigned using assigned reference calibrators.
Internal Material Gravimetrically Prepared: The CVMs are traceable to an internal material which has been gravimetrically prepared.
Statistical Derivation: Target Mean and ± 2 Standard Deviation (SD) are used to establish Guideline Ranges.

8. Sample Size for Training Set

No explicit "training set" in the context of machine learning. The "Value Assignment" process is analogous to establishing the ground truth/reference for the CVMs. This involved:

6 levels of IGF-I calibrators (used internally, not commercialized).
2 levels of commercially available controls.
60 samples (10 spiked samples and 50 normal patient samples).

9. How Ground Truth for Training Set was Established

The ground truth (value assignment) for the CVMs was established using:

Assigned reference calibrators.
CVM dose values generated using curves from these assigned reference calibrators.
CVM values calculated from recovered values for each run on each instrument independently and then averaged across all systems.
Quality control performed by calculating recovery of patient samples and controls using the assigned CVM values, ensuring controls fall within their target ranges.

IMMULITE® 2000 Prolactin Calibration Verification Material

1. Table of Acceptance Criteria and Reported Device Performance

Level	Acceptance Criteria (Dose Value)	Reported Performance (Guideline ±2SD Range)	Target Mean (ng/mL)	Standard Deviation (SD)
LPRCVM1	Within ±10% of assigned dose (implied for all levels as per general criteria)	0.00 ≤0.5 ng/mL	0.00*	-
LPRCVM2	Within ±10% of assigned dose	7.10 - 10.0 ng/mL	8.55	0.725
LPRCVM3	Within ±10% of assigned dose	36.7 - 48.7 ng/mL	42.7	3.0
LPRCVM4**	Within ±10% of assigned dose (after dilution for target value within reportable range)	-	195	-
80% LPRCVM4 + 20% LPRCVM1	Within ±10% of assigned dose	131 - 181 ng/mL	156*	12.5
Part 2	Dose value of controls within 2SD of the control target value when generated from stability calibrator curve.	-	-	-

Note: The reported performance "Guideline ±2SD Range" is derived from the established Target Mean and Standard Deviation, and suggests the expected range within which the CVMs should perform. The exact demonstration of conformity to the ±10% acceptance criteria based on this study is not explicitly stated as a pass/fail within this summary, but the derived ranges imply performance within expected limits. LPRCVM4 requires dilution for its target value to be within the reportable range of the assay.

2. Sample Size and Data Provenance for Test Set

Sample Size:
- 27 replicates for each CVM level (9 runs and 3 replicates per run).
- 8 IMMULITE 2000 systems.
- 4 different reagent kit lots.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). Implied to be internal, prospective testing by the manufacturer.

3. Number of Experts and Qualifications for Ground Truth of Test Set

Not applicable for this type of device (calibration verification material). The "ground truth" refers to the assigned dose values and established statistically derived ranges.

4. Adjudication Method for Test Set

Not applicable for this type of device. The evaluation is based on quantitative measurements against predefined statistical criteria.

5. MRMC Comparative Effectiveness Study

No. This is not a comparative effectiveness study involving human readers.

6. Standalone Performance Study (Algorithm Only)

7. Type of Ground Truth Used

Assigned Reference Calibrators: The CVMs are value assigned using assigned reference calibrators.
3rd IS 84/500: The CVMs are traceable to this international standard.
Statistical Derivation: Target Mean and ± 2 Standard Deviation (SD) are used to establish Guideline Ranges.

8. Sample Size for Training Set

No explicit "training set" in the context of machine learning. The "Value Assignment" process is analogous to establishing the ground truth/reference for the CVMs. This involved:

8 levels of Prolactin calibrators (used internally, not commercialized).
6 levels of commercially available controls.
30 samples (10 normal patients and 20 spiked normal patient samples).

9. How Ground Truth for Training Set was Established

The ground truth (value assignment) for the CVMs was established using:

Assigned reference calibrators.
CVM dose values generated using curves from these assigned reference calibrators.
CVM values calculated from recovered values for each run on each instrument independently and then averaged across all systems.
Quality control performed by calculating recovery of patient samples and controls using the assigned CVM values.

Summary

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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: k140818_______________________________________________________________________________________________________________________________________

1.	SubmitterMailing Address:	Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591
	Contact Person:Phone Number:Fax Number:E-mail Address:Date Prepared:	Ernest JosephSenior Manager, Regulatory Affairs(914)-524-2431(914)-524-2101ernest.joseph@siemens.comMarch 31, 2014
	2. Device NameProprietary Name:Measurand:Type of Test:Regulation Section:Classification:Products Code:Panel:	IMMULITE® 2000 Free T4 Calibration Verification MaterialQuality Control materials for IMMULITE® 2000 Free T4 assayCalibration Verification Material (CVM) for IMMULITE® 2000Free T4 assay21 CFR 862.1660, Quality Control MaterialClass I ReservedJJX - Single (Specified) Analyte Controls (Assayed andUnassayed)Clinical Chemistry (75)
	3. Predicate Device NamePredicate 510(k) No:	IMMULITE® 2000 Total T4 Calibration Verification Material(CVM)K133124
	4. Device Description:	The IMMULITE® 2000 Free T4 Calibration Verification Material(CVM) contains one set of four vials each ImL. CVMIcontains alyophilized processed human serum matrix with 1.58% sodiumazide and preservative and CVM2, CVM3, and CVM4 containvarious levels of lyophilized Free T4 in a processed human serummatrix with 1.58% sodium azide and preservative. CVMs aresupplied frozen in a lyophilized form.
	5. Intended Use:Indication for Use:	See Indications for Use Statement belowThe IMMULITE® Free T4 Calibration Verification Material(CVM) for in vitro diagnostic use in the verification of calibrationof the IMMULITE Free T4 assay on the IMMULITE 2000 systems
	Special Conditions forUse Statement(s):Special InstrumentRequirements:	For prescription use onlyIMMULITE® 2000 Systems

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6. Technological Characteristics and Substantial Equivalence Comparison with Predicate:

A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Free T4 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 Free T4 CVM	Predicate DeviceIMMULITE 2000 Total T4 CVM
IntendedUse	The IMMULITE® Free T4Calibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Free T4 assay on theIMMULITE 2000 systems.	The IMMULITE® Total T4Calibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Total T4 assay on theIMMULITE 2000 systems
StorageStability	<-20°C	Same
	Stable unopened until theexpiration date	Same
Levels	4	Same
Matrix	Human Serum with preservatives	Same
Use	Single Use Only	Same
	DIFFERENCES
	Candidate DeviceIMMULITE 2000 Free T4 CVM	Predicate DeviceIMMULITE 2000 Total T4 CVM
Analyte	Free T4	Total T4
Form	Lyophilized	Liquid

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.

Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Free T4 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 Calibration Verification Materials are stable up to 4 years when stored at -20°C prior to opening and stable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution.

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Stability Protocol Summary:

The CVM study protocols are run as part of the calibrator stability testing. As summarized in Table 2, the testing was run in duplicate (at the minimum) and contains time-points at which the testing was performed.

CVM Level	Time-Points(Days)
LFT4CVM1	1	1095	1280	1460
LFT4CVM2	1	1095	1280	1460
LFT4CVM3	1	1095	1280	1460
LFT4CVM4	1	1095	1280	1460

Table 2: Stability Protocol Summary

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Free T4 requires dose value of stability CVMs to fall between ±10% of assigned dose for CVM level 2 and 3 and within ±15% of assigned dose for level 4. Part 2 review limits criteria requires 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% for levels 2 and 3 and 15% for level 4 then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE Free T4 CVMs are traceable to an internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE Free T4 CVMs are 4 level materials which are a subset of 6 level Total Free T4 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Free T4 reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The CVMs are manufactured using qualified materials and measurement procedures. 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. Six levels of commercially available controls and 30 normal samples were used to validate CVM value assignments.

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Expected Values/Target Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run, 5 different reagent kit lots and 9 IMMULITE 2000 systems. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The target values are provided in the IMMULITE® 2000 CVM Calibration Material lotspecific value card. The expected assay range is 0.3 - 6 ng/dL. The target values in Table 3 can be considered as guidelines.

Analyte targetlevels	CVM Level	TargetMean(ng/dL)	StandardDeviation(SD)	Guideline ±2SD Range(ng/dL)
	LFT4CVM1	0.00*	-	≤0.3
	LFT4CVM2	1.51	0.09	1.69
	LFT4CVM3	2.90	0.145	3.19
	LFT4CVM4	6.85*	0.515	7.88
Assay Range	0.3 - 6 ng/dL

Table 3: Analyte Target Range Values
---------------------------------------	--	--	--	--	--

*Note: when CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software. If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.

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
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

8. Conclusion:

The IMMULITE® 2000 Free T4 Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. 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 Free T4 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:

1. Submitter	Siemens Healthcare Diagnostics Inc.
Mailing Address:	511 Benedict AvenueTarrytown, NY 10591
Contact Person:	Ernest Joseph
	Senior Manager, Regulatory Affairs
Phone Number:	(914)-524-2431
Fax Number:	(914)-524-2101
E-mail Address:	errnest.joseph@siemens.com
Date Prepared:	March 31, 2014
2. Device Name
Proprietary Name:	IMMULITE® 2000 IGF-I Calibration Verification Material
Measurand:	Quality Control materials for IMMULITE® 2000 IGF-I assay
Type of Test:	Calibration Verification Material (CVM) for IMMULITE® 2000 IGF-I 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	IMMULITE 2000 HCG CVM
Predicate 510(k) No:	K133128
4. Device Description:	The IMMULITE® 2000 IGF-I Calibration Verification Material (CVM) contains one set of four vials, 2mL (CVM1) each. CVM1 contains a processed bovine protein/buffer matrix with preservatives. CVM2, CVM3, and CVM4 contain various levels of IGF-I in a processed bovine protein/buffer matrix with preservatives. The CVMs are supplied frozen in a liquid form.
5. Intended Use:
Indication for Use:	See Indications for Use Statement belowThe IMMULITE® IGF-I Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE IGF-I assay on the IMMULITE 2000 systems

Special Conditions for

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Image /page/5/Picture/0 description: The image contains the word "SIEMENS" in all capital letters. The text is written in a bold, sans-serif font. The letters are black against a white background.

Use Statement(s):	For prescription use only
Special InstrumentRequirements:	IMMULITE® 2000 Systems

1. Technological Characteristics and Substantial Equivalence Comparison with Predicate:
  A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 IGF-I 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 IGF-I CVM	Predicate DeviceIMMULITE 2000 HCG CVM
IntendedUse	The IMMULITE® IGF-I CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration of the IMMULITE IGF-Iassay on the IMMULITE 2000 systems	The IMMULITE® HCG CalibrationVerification Material (CVM) is for invitro diagnostic use in the verificationof calibration of the IMMULITEHCG assay on the IMMULITE 2000systems
Form	Liquid	Same
Levels	4	Same
Stability	Stable unopened until the expiration date	Same
Storage	≤-20°C	Same
Use	Single Use Only	Same

	DIFFERENCES
	Candidate DeviceIMMULITE 2000 IGF-I CVM	Predicate DeviceIMMULITE 2000 HCG CVM
Analyte	IGF-I	HCG
Matrix	Bovine protein/buffer with preservatives	Human serum with preservatives

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.

Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 IGF-I 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 Calibration Verification Materials are stable up to 2.5 years when stored at -20°C prior to opening, and for 8 hours at ambient temperature (room temperature) after opening.

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Stability Protocol Summary:

CVM Level	Time-Points(Days)
LGFCVM1	1	365	730	912
LGFCVM2	1	365	730	912
LGFCVM3	1	365	730	912
LGFCVM4	1	365	730	912

Table 2: Stability Protocol Summary

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE IGF-I requires dose value of stability CVMs to fall between ±10% of the assigned dose. Part 2 review limits criteria 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% for each level then additional data review is conducted using part 2 criteria.

Traceability:

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

Value Assignment:

The IMMULITE IGF-I CVMs are 4 level materials which are a subset of 6 level IGF-I calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of IGF-I reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. 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. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges. Two levels of commercially available controls and 60 samples (10 spiked samples and 50 normal patient samples) were used to validate CVM value assignments.

Expected Values/Target Values/Reference Range:

The CVMs are manufactured using qualified materials and measurement procedures. The IGF-I CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run on 7 IMMULITE 2000 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. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and

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controls using the assigned CVM values. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected assay range is Up to 1600 ng/mL . The target values in Table 3 can be considered as guidelines.

Analyte targetlevels	CVM Level	TargetMean(ng/mL)	StandardDeviation(SD)	Guideline ±2SD Range(ng/mL)
	LGFCVM1	0.00	-	≤25.00
	LGFCVM2	34.7	2.8	29.1
	LGFCVM3	237	15.5	206
	LGFCVM4	1727*	86.5	1554
Assay Range	Up to 1600 ng/mL

Table 3: Analyte Target Range Levels

*Note: when CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software.

If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.

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

8. Conclusion:

The IMMULITE® 2000 IGF-1 Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. 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 IGF-I 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: K140818

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:

1. Predicate Device Name
  Predicate 510(k) No:
1. Device Description:
1. Intended Use: Indication for Use:
  Special Conditions for Use Statement(s):

Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591

Ernest Joseph Senior Manager, Regulatory Affairs (914)-524-2431 (914)-524-2101 ernest.joseph(@siemens.com March 31, 2014

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

IMMULITE® 2000 Growth Hormone Calibration Verification Material K133128

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

For prescription use only

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Special Instrument Requirements:

IMMULITE® 2000 Systems

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

SIMILARITIES
	Candidate DeviceIMMULITE 2000 Prolactin CVM	Predicate DeviceIMMULITE 2000 Growth HormoneCVM
IntendedUse	The IMMULITE® Prolactin CalibrationVerification Material (CVM) is for invitro diagnostic use in the verification ofcalibration of the IMMULITE Prolactinassay on the IMMULITE 2000 systems.	The IMMULITE® Growth HormoneCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE Growth Hormone assayon the IMMULITE 2000 systems
Form	Lyophilized	Same
Storage	2-8°C	Same
Stability	Stable unopened until theexpiration date	Same
Levels	4	Same
Matrix	Equine Serum with preservatives	Same
Use	Single Use Only	Same

			Table 1: Substantial Equivalence Comparison
--	--	--	---------------------------------------------

	DIFFERENCES
	Candidate DeviceIMMULITE 2000 Prolactin CVM	Predicate DeviceIMMULITE 2000 Growth HormoneCVM
Analyte	Prolactin	Growth Hormone

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.

Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Prolactin CVM to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 3 years when stored at 2-8°C prior to opening and stable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution.

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Stability Protocol Summary:

Table 2: Stability Protocol Summary

CVM Level	Time-Points(Days)
LPRCVM1	1	548	912	1095
LPRCVM2	1	548	912	1095
LPRCVM3	1	548	912	1095
LPRCVM4	1	548	912	1095

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Prolactin requires dose value of stability CVM to fall between ± 10% of assigned dose. Part 2 review limits criteria requires 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% for each level then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE Prolactin CVMs are traceable to 3rd IS 84/500. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE® 2000 Prolactin CVMs are 4 level materials which are a subset of 8 level Prolactin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Prolactin reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. 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 and controls using the assigned CVM values. Six levels of commercially available controls and 30 samples (10 normal patients and 20 spiked normal patient samples) were used to validate CVM value assignments.

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Expected Values/Target Values/Reference Range:

The Prolactin CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run, 8 IMMULITE 2000 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 and controls using the assigned CVM values. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected assay range is 0.5 - 150 ng/mL. The target values in Table 3 can be considered as guidelines.

Analyte targetlevels	Level	TargetMean(ng/mL)	StandardDeviation(SD)	Guideline ±2SD Range(ng/mL)
	LPRCVM1	0.00*	-	0.00 ≤0.5
	LPRCVM2	8.55	0.725	7.10 10.0
	LPRCVM3	42.7	3.0	36.7 48.7
	LPRCVM4**	195	-	-
	80% LPRCVM4 +20% LPRCVM1	156*	12.5	131 181
Assay Range	0.5 - 150 ng/mL

Table 3: Analyte Target Range Levels

*Note When CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software.

If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.

** Note: LPRCVM4 requires dilution to ensure the target value is within +10% 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 Quality Control Material .

Proposed Labeling:

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

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8. Conclusion:

The IMMULITE® 2000 Prolactin Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. 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 Prolactin 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/13/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an image of an eagle with its wings spread, with three lines extending from the eagle's head.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

May 1, 2014

SIEMENS HEALTHCARE DIAGNOSTICS INC. MR.ERNEST JOSEPH SENIOR MANAGER, REGULATORY AFFAIRS 511 BENEDICT AVE. TARRYTOWN NY 10591

Rc: K140818

Trade/Device Name: IMMULITE® 2000 Free T4 Calibration Verification Material, IMMULITE® 2000 IGF-1 Calibration Verification Material, IMMULITE® 2000 Prolactin Calibration Verification Material Regulation Number: 21 CFR 862,1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: 1, Reserved Product Code: JJX Dated: March 31, 2014 Received: April 1. 2014

Dear Mr. Ernest Joseph:

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

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

Please be advised that FDA 's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803): good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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Page 2-Mr. Ernest Joseph

electronic product radiation control provisions (Sections 531-542 of the Act): 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/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.lda.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 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.

Sincerely vours.

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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

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

510(k) Number (if known) K140818

Device Name

IMMULITE®2000 Free T4 Calibration Material, IMMULITE®2000 IGF-1 Calibration Verification Material, and IMMULITE®2000 Prolactin Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® Free T4 Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Free T4 assay on the IMMULITE 2000 systems.

The IMMULITE® IGF-1 Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE IGF-1 assay on the IMMULITE 2000 systems.

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

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

Prescription Use (Part 21 CFR 801 Subpart D)

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

. :

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)

Yung W. Chan -S

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

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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.