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

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

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

Device Description

IMMULITE® 2000 C-Peptide Calibration Verification Material (CVM) contains one set of four vials each 2mL. CVM1 contains a lyophilized buffered human albumin with bovine protein. 0.197% sodium azide and preservative CVM2, CVM3 and CVM4 contain various levels of lyophilized C-Peptide in buffered human albumin with bovine protein, 0.197% sodium azide and preservative. CVMs are supplied frozen in a lyophilized form.

IMMULITE® 2000 SHBG Calibration Verification Material (CVM) contains one set of four vials, 2mL (CVM1) and 2 mL (CVM2, CVM3 and CVM4) each. CVM1 contains a lyophilized buffered bovine protein/buffer matrix with 3.64% sodium azide and preservative. CVM2, CVM3, and CVM4 contain various levels of lyophilized SHBG in bovine protein/buffer matrix with 3.64% sodium azide and preservative CVMs are supplied frozen in lyophilized form.

IMMULITE® 2000 Total Testosterone Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM1 contains processed human serum with 0.98% sodium azide and other preservative. CVM2, CVM3, and CVM4 contain various levels of testosterone in processed human serum with 0.98% sodium azide and other preservative. The CVMs are supplied frozen in a liquid form.

AI/ML Overview

The provided text describes three distinct devices: IMMULITE® 2000 C-Peptide, SHBG, and Total Testosterone Calibration Verification Materials (CVMs). Each device has its own acceptance criteria and associated performance testing. I will address each of them separately.

1. IMMULITE® 2000 C-Peptide Calibration Verification Material

Table of Acceptance Criteria and Reported Device Performance (Stability Studies):

CVM Level	Acceptance Criteria (Shelf Life)	Acceptance Criteria (Open Vial)	Reported Performance (Shelf Life)	Reported Performance (Open Vial)
LPEPCVM1	Not explicitly stated (likely qualitative, e.g., no significant change)	Same as Shelf Life Acceptance Criteria	Stable up to 6 years at 2-8°C	Stable for 8 hours at 15-25°C
LPEPCVM2	Dose value to fall between ±15% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 6 years at 2-8°C	Stable for 8 hours at 15-25°C
LPEPCVM3	Dose value to fall between ±10% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 6 years at 2-8°C	Stable for 8 hours at 15-25°C
LPEPCVM4	Dose value to fall between ±15% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 6 years at 2-8°C	Stable for 8 hours at 15-25°C

Study Details for C-Peptide CVM:

1. Sample sized used for the test set and the data provenance:
- Shelf Life Stability: Data points at 1 day, 1642 days (~4.5 years), 1825 days (5 years), and 2190 days (6 years). Testing was run in duplicate (at minimum) for each CVM level.
- Open Vial Stability: Data points at 0, 2, 4, and 8 hours for each CVM level.
- Value Assignment: 27 replicates (9 runs, 3 replicates per run) using 5 different reagent kit lots and 9 IMMULITE 2000 systems. 6 levels of commercially available controls and 59 normal patient samples were used to validate CVM value assignments.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). Implied to be prospective, internal performance testing.
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This is for a calibration verification material, where internal reference methods and defined target values form the "ground truth."
3. Adjudication method for the test set: Not applicable. Performance is based on pre-defined analytical acceptance criteria.
4. 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 quality control material, not an AI-assisted diagnostic device.
5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not applicable. This is an in vitro diagnostic material. The device's performance is its ability to maintain its assigned values over time and conditions.
6. The type of ground truth used (expert consensus, pathology, outcomes data, etc): The "ground truth" for CVMs is based on assigned reference calibrators which are traceable to WHO 1st IRP 84/510. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values against their target ranges.
7. The sample size for the training set: Not applicable. This is not a machine learning/AI device with a training set. The term "training set" is generally used in the context of supervised learning for AI.
8. How the ground truth for the training set was established: Not applicable.

2. IMMULITE® 2000 SHBG Calibration Verification Material

Table of Acceptance Criteria and Reported Device Performance (Stability Studies):

CVM Level	Acceptance Criteria (Shelf Life)	Acceptance Criteria (Open Vial)	Reported Performance (Shelf Life)	Reported Performance (Open Vial)
LSHCVM1	Not explicitly stated (likely qualitative, e.g., no significant change)	Same as Shelf Life Acceptance Criteria	Stable up to 9 years at 2-8°C	Stable for 8 hours at 15-25°C
LSHCVM2	Dose value to fall between ±10% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 9 years at 2-8°C	Stable for 8 hours at 15-25°C
LSHCVM3	Dose value to fall between ±10% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 9 years at 2-8°C	Stable for 8 hours at 15-25°C
LSHCVM4	Dose value to fall between ±20% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 9 years at 2-8°C	Stable for 8 hours at 15-25°C

Study Details for SHBG CVM:

1. Sample sized used for the test set and the data provenance:
- Shelf Life Stability: Data points at 1 day, 2190 days (6 years), 2555 days (7 years), and 3285 days (9 years). Testing was run in duplicate (at minimum) for each CVM level.
- Open Vial Stability: Data points at 0, 2, 4, and 8 hours for each CVM level.
- Value Assignment: 27 replicates (9 runs, 3 replicates per run) on 8 IMMULITE 2000 systems using 1 reagent kit lot. 4 levels of commercially available controls and 28 normal patient samples were used to validate CVM value assignments.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). Implied to be prospective, internal performance testing.
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. Analytical performance based on pre-defined criteria.
3. Adjudication method for the test set: Not applicable.
4. 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.
5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not applicable.
6. The type of ground truth used (expert consensus, pathology, outcomes data, etc): The "ground truth" for CVMs is based on assigned reference calibrators traceable to an internal gravimetrically prepared material. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values against their target ranges.
7. The sample size for the training set: Not applicable.
8. How the ground truth for the training set was established: Not applicable.

3. IMMULITE® 2000 Total Testosterone Calibration Verification Material

Table of Acceptance Criteria and Reported Device Performance (Stability Studies):

CVM Level	Acceptance Criteria (Shelf Life)	Acceptance Criteria (Open Vial)	Reported Performance (Shelf Life)	Reported Performance (Open Vial)
LTWCVMI	Not explicitly stated (likely qualitative, e.g., no significant change)	Same as Shelf Life Acceptance Criteria	Stable up to 26 months at -20°C	Stable for 6 hours at 15-25°C
LTWCVM2	Dose value to fall between ±15% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 26 months at -20°C	Stable for 6 hours at 15-25°C
LTWCVM3	Dose value to fall between ±10% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 26 months at -20°C	Stable for 6 hours at 15-25°C
LTWCVM4	Dose value to fall between ±9% of assigned dose; OR within 2SD of control target value (Part 2)	Same as Shelf Life Acceptance Criteria	Stable up to 26 months at -20°C	Stable for 6 hours at 15-25°C

Study Details for Total Testosterone CVM:

1. Sample sized used for the test set and the data provenance:
- Shelf Life Stability: Data points at 1 day, 182 days (~6 months), 365 days (1 year), and 790 days (~26 months). Testing was run in duplicate (at minimum) for each CVM level.
- Open Vial Stability: Data points at 0, 2, 4, and 8 hours for each CVM level.
- Value Assignment: 27 replicates (9 runs, 3 replicates per run) on 9 IMMULITE 2000 systems using 5 different reagent kit lots. 6 levels of commercially available controls and 32 samples (23 spiked samples, 4 normal female, and 5 normal male samples) were used to validate CVM value assignments.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). Implied to be prospective, internal performance testing.
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. Analytical performance based on pre-defined criteria.
3. Adjudication method for the test set: Not applicable.
4. 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.
5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Not applicable.
6. The type of ground truth used (expert consensus, pathology, outcomes data, etc): The "ground truth" for CVMs is based on assigned reference calibrators traceable to an internal gravimetrically prepared material. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values against their target ranges.
7. The sample size for the training set: Not applicable.
8. How the ground truth for the training set was established: Not applicable.

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: K140541

Submitter Mailing Address: Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown, NY 10591 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): Special Instrument Requirements:

Garo Mimaryan, MS, RAC Senior Regulatory Affairs Specialist (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com March 27. 2014

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

IMMULITE® 2000 Growth Hormone Calibration Verification Material (CVM) K133128

The C-Peptide Calibration Verification Material (CVM) contains one set of four vials each 2mL. CVM1 contains a lyophilized buffered human albumin with bovine protein. 0.197% sodium azide and preservative CVM2, CVM3 and CVM4 contain various levels of lyophilized C-Peptide in buffered human albumin with bovine protein, 0.197% sodium azide and preservative. CVMs are supplied frozen in a lyophilized form

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

For prescription use only IMMULITE® 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 C-Peptide 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 C-Peptide CVM	Predicate DeviceIMMULITE 2000 Growth HormoneCVM
IntendedUse	The IMMULITE® C-PeptideCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE C-Peptide assay on theIMMULITE 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
Use	Single Use Only	Same
	DIFFERENCES
	Candidate DeviceIMMULITE 2000 C-Peptide CVM	Predicate DeviceIMMULITE 2000 Growth HormoneCVM
Analyte	C-Peptide	Growth Hormone
Matrix	Human Albumin* with preservatives	Equine Serum with preservatives

*This material was tested negative for HIV-1, HIV-2 and hepatitis by FDA approved methods.

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 C-Peptide 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 6 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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Shelf life 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.

Table 2: Shelf life Stability Protocol Summary

CVM Level	Time-Points(Days)
LPEPCVM1	1	1642	1825	2190
LPEPCVM2	1	1642	1825	2190
LPEPCVM3	1	1642	1825	2190
LPEPCVM4	1	1642	1825	2190

Shelf life Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE C-Peptide criteria which require dose value of stability CVM to fall between ±15% of assigned dose for CVM levels 2 and 4 and ±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 ±15% for levels 2 and 4 and ±10% for level 3 then an additional data review is conducted using part 2 criteria

Open Vial Stability Protocol Summary:

As summarized in Table 3, The C-Peptide CVMs were tested at 2-hourly intervals for up to 9 hours at room temperature (ambient) conditions.

Table 3: Open Vial Stability Protocol Summary

CVM Level
LPEPCVM1	2	4	8
LPEPCVM2	2	4	8
LPEPCVM3	2	4	8
LPEPCVM4	2	4	8

Open Vial Stability Acceptance Criteria Summary:

The Acceptance Criteria for the Open Vial Stability are the Shelf life Stability Acceptance criteria.

Traceability:

The IMMULITE C-Peptide CVMs are traceable to WHO 1st IRP 84/510. The CVMs are manufactured using qualified materials and measurement procedures.

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Value Assignment:

The IMMULITE C-Peptide CVMs are 4 level materials which are a subset of 10 level Total C-Peptide calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of C-Peptide 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. The controls must fall within their target ranges. Six levels of commercially available controls and 59 normal patient samples were used to validate CVM value assignments.

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 verification Material lotspecific value card. The expected assay range is 0.1 - 20 ng/mL. The target values in Table 4 can be considered as guidelines.

Analyte targetlevels	CVM Level	TargetMean(ng/mL)	StandardDeviation(SD)	Target Range(ng/mL)
	LPEPCVM1	0.00	-	≤0.1
	LPEPCVM2	0.520	0.039	0.442	0.598
	LPEPCVM3	8.85	0.4425	7.97	9.74
	LPEPCVM4	25.6	-	-
	( 80% LPEPCVM4 +20% LPEPCVM1 )	20.5	1.55	17.4	23.6
Assay Range	0.1-20 ng/mL

Table 4: Analyte Target Range Values

Assay Range | 0.1 - 20 ng/mL

*Note: LPEPCVM4 requires dilution to ensure the target value is within +10% of the top of the reportable range of the assay.

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

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9. Conclusion:

The IMMULITE® 2000 C-Peptide 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 C-Peptide 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: K140541

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:

4. Device Description:

1. Intended Use: Indication for Use:
  Special Conditions for Use Statement(s): Special Instrument Requirements:

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

Garo Mimaryan, MS, RAC Senior Regulatory Affairs Specialist (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com March 27, 2014

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

IMMULITE 2000 Growth Hormone CVM K133128

See Indications for Use Statement below

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

For prescription use only IMMULITE® 2000 Systems

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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 SHBG Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.

SIMILARITIES
	Candidate DeviceIMMULITE 2000 SHBG CVM	Predicate DeviceIMMULITE 2000 Growth HormoneCVM
IntendedUse	The IMMULITE® SHBGCalibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE SHBG assay on theIMMULITE 2000 systems	The IMMULITE® Growth HormoneCalibration Verification Material (CVM)is for in vitro diagnostic use in theverification of calibration of theIMMULITE Growth Hormone assay onthe IMMULITE 2000 systems
Form	Lyophilized	Same
Storage	2-8°C	Same
Stability	Stable unopened until theexpiration date	Same
Levels	4	Same
Use	Single Use Only	Same

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

	DIFFERENCES
	Candidate DeviceIMMULITE 2000 SHBG CVM	Predicate DeviceIMMULITE 2000 Growth HormoneCVM
Analyte	SHBG	Growth Hormone
Matrix	Buffered bovine/protein withpreservatives	Equine 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 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 SHBG 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 9 years when stored at 2-8°C prior to opening and stable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution.

Shelf Life Stability Protocol Summary:

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CVM Level	Time-Points(Days)
LSHCVM1	1	2190	2555	3285
LSHCVM2	1	2190	2555	3285
LSHCVM3	1	2190	2555	3285
LSHCVM4	1	2190	2555	3285

Table 2: Shelf Life Stability Protocol Summary

Shelf Life Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE SHBG Calibration Material (CVM) are in 2 parts. Part 1 consists of the guideline acceptance criteria which require dose value of stability CVM to fall between ±10% of assigned dose for CVM levels 2 & 3 and ±20% of assigned dose 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 ±10% for levels 2 & 3 and ±20% for level 4 then additional data review is conducted using part 2 criteria.

Open Vial Stability Protocol Summary:

As summarized in Table 3, SHBG CVMs were tested at 2-hourly intervals for up to 9 hours at room temperature (ambient) conditions.

Table 3: Open Vial Stability Protocol Summary

CVM Level
LSHCVM1	2	4	8
LSHCVM2	2	4	8
LSHCVM3	2	4	8
LSHCVM4	2	4	8

Open Vial Stability Acceptance Criteria Summary:

The Acceptance Criteria for the Open Vial Stability are the Shelf life Stability Acceptance criteria.

Traceability:

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

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Value Assignment:

The IMMULITE SHBG CVMs are 4 level materials which are a subset of 9 level SHBG calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of SHBG 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. Four levels of commercially available controls and 28 normal patient samples were used to validate CVM value assignments. 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

Expected Values/Target Values/Reference Range:

The CVMs are manufactured using qualified materials and measurement procedures. The SHBG CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run on 8 IMMULITE 2000 systems and 1 reagent kit lot. 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 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 2-180 nmol/L. The target values in Table 4 can be considered as guidelines.

Analyte targetlevels	CVM Level	TargetMean(nmol/L)	StandardDeviation(SD)	Target Range(nmol/L)
	LSHCVM1	0.00	-	0.00	≤2.0
	LSHCVM2	6.00	0.3	5.40	6.60
	LSHCVM3	47.2	2.6	42	52.4
	*LSHCVM4	216	-	-	-
	(85% LSHCVM4 +15% LSHCVM1)	184	18.5	147	221
Assay Range	2 - 180 nmol/L

Table 4: Analyte Target Range Levels

*Note: LSHCVM4 requires dilution to ensure the target value is within +10% of the reportable range of the assay.

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 .

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Proposed Labeling:

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

9. Conclusion:

The IMMULITE® 2000 SHBG 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 SHBG 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: K140541

Special Conditions for

Use Statement(s): Special Instrument

Requirements:

Submitter	Siemens Healthcare Diagnostics Inc.
Mailing Address:	511 Benedict AvenueTarrytown, NY 10591
Contact Person:	Garo Mimaryan, MS, RACSenior Regulatory Affairs Specialist
Phone Number:	(914)-524-3270
Fax Number:	(914)-524-2101
E-mail Address:	garo.mimaryan@siemens.com
Date Prepared:	March 27, 2014
2. Device Name	IMMULITE® 2000 Total Testosterone Calibration Verification Material
Proprietary Name:	Quality Control materials for IMMULITE 2000 Total Testosterone
Measurand:	Calibration Verification Material (CVM) for IMMULITE® 2000
Type of Test:	Total Testosterone 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 Calibration Verification Material
Predicate 510(k) No:	K133128
4. Device Description:	IMMULITE® 2000 Total Testosterone Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM1 contains processed human serum with 0.98% sodium azide and other preservative. CVM2, CVM3, and CVM4 contain various levels of testosterone in processed human serum with 0.98% sodium azide and other preservative. The CVMs are supplied frozen in a liquid form.
5. Intended Use:Indication for Use:	See Indications for Use Statement below

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

For prescription use only IMMULITE® 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 Total Testosterone 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 Total TestosteroneCVM	Predicate DeviceIMMULITE 2000 HCG CVM
IntendedUse	The IMMULITE® Total TestosteroneCalibration Verification Material (CVM)is for in vitro diagnostic use in theverification of calibration of theIMMULITE Total Testosterone assay onthe 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
Matrix	Human Serum* with preservatives	Same
Stability	Stable unopened until the expiration date	Same
Storage	≤20°C	Same
Use	Single Use Only	Same
	DIFFERENCES
	DIFFERENCES
	Candidate DeviceIMMULITE 2000 Total TestosteroneCVM	Predicate DeviceIMMULITE 2000 HCG CVM
Analyte	Testosterone	HCG

This material was tested negative for HIV-1, HIV-2 and hepatitis by FDA approved methods,

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 Total Testosterone 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 26 months when stored at -20°C prior to opening and stable for 6 hours at room (ambient) temperature (15-25°C).

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Shelf Life Stability Protocol Summary:

Table 2: Shelf Life Stability Protocol Summary

CVM Level	Time-Points(Days)
LTWCVMI	1	182	365	790
LTWCVM2	1	182	365	790
LTWCVM3	1	182	365	790
LTWCVM4	1	182	365	790

Shelf Life Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Total Testosterone criteria which require dose value of stability CVM to fall between ±15% of assigned dose for CVM level 2, ±10% of assigned dose for CVM level 3 and ±9% of assigned dose 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 ±15% for level 2, ±10% for level 3 and ±9% for level 4 then additional data review is conducted using part 2 criteria.

Open Vial Stability Protocol Summary:

As summarized in Table 3, The Total Testosterone CVMs were tested at 2-hourly intervals for up to 9 hours at room temperature (ambient) conditions.

CVM Level
LTWCVMI	2	4	8
LTWCVM2	2	4	8
LTWCVM3	2	4	8
LTWCVM4	2	4	8

Table 3: Open Vial Stability Protocol Summary

Open Vial Stability Acceptance Criteria Summary:

The Acceptance Criteria for the Open Vial Stability are the Shelf life Stability Acceptance criteria.

Traceability:

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

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Value Assignment:

The IMMULITE® 2000 Total Testosterone CVMs are 4 level materials which are a subset of 9 level Total Testosterone calibrators are not commercialized but are used internally during manufacture and release testing of Total Testosterone 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 32 samples (23 spiked samples, 4 normal female and 5 normal male samples) were used to validate CVM value assignments. 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

Expected Values/Target Values/Reference Range:

The Total Testosterone CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run, 9 IMMULITE 2000 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 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 20-1600 ng/dL. The target values in Table 4 can be considered as guidelines.

Analyte targetlevels	Level	TargetMean(ng/dL)	StandardDeviation(SD)	Target Range(ng/dL)
	LTWCVMI	0.00	-	0.00 $≤$ 0.20
	LTWCVM2	73.5	13.675	46.3 101
	LTWCVM3	405	36.5	332 478
	*LTWCVM4	2016	-	-
	(80% LTWCVM4 +20% LTWCVMI)	1613	121	1371 1855
Assay Range	20 - 1600 ng/dL

Table 4: Analyte Target Range Levels

*Note: LTWCVM4 requires dilution to ensure the target value is within +10% of the top of the reportable range of

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 .

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Proposed Labeling:

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

9. Conclusion:

The IMMULITE® 2000 Total Testosterone Calibration 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 Total Testosterone 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/15/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized symbol resembling three abstract shapes that are stacked on top of each other.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

April 1, 2014

SIEMENS HEALTHCARE DIAGNOSTICS INC. GARO MIMARYAN SENIOR REG. AFFAIRS SPECIALIST 511 BENEDICT AVE. TARRYTOWN NY 10591

Rc: K140541

Trade/Device Name: IMMULITE® 2000 C-Peptide Calibration Verification Material, IMMULITE® 2000 SHBG Calibration Verification Material. IMMULITE® 2000 Total Testosterone Calibration Verification Matcrial Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I. Reserved Product Code: JJX

Dated: February 28, 2014 Received: March 4, 2014

Dear Garo Mimaryan:

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 cither 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 (OS) regulation (21 CFR Part 820); and if applicable, the

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Page 2-Garo Mimaryan

clectronic 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/McdicalDevices/Safety/Reportal?roblem/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/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Courtney H. Lias -S

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

Enclosure

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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) k 140541

Device Name

IMMULITE®2000 C-Peptide Calibration Material, IMMULITE®2000 SHBG Calibration Verification Material, and IMMULITE®2000 Total Testosterone Calibration Verification Material

Indications for Use (Describe)

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

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

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

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

2 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

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

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

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

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

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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.