IMMULITE 2000 LH Calibration Verification Material (CVM), IMMULITE 2000 Free T3 Calibration Verification Material (CVM), IMMULITE 2000 Gastrin Calibration Verification Material (CVM) by Siemens Healthcare Diagnostics Inc.

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

The IMMULITE® 2000 Free T3 Calbration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Free T3 assay on the IMMULITE 2000 systems

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

Device Description

The IMMULITE 2000 LH Calibration Verification Material (CVM) contains one set of four vials each 3.0mL after reconstitution. CVM1 contains lyophilized bovine serum with preservatives. CVM2, CVM3 and CVM4 contain various levels of LH antigen from human pituitary glands in a lyophilized bovine serum matrix with preservatives.

IMMULITE® 2000 Free T3 Calibration Verification Material (CVM) contains one set of four vials. CVM1 contains 4.0 mL processed lyophilized human serum with preservatives after reconstitution. CVM2, CVM3 and CVM4 contain 2.0mL/vial of various levels of 3,31 Triiodo-L-Thyronine (Free Acid) in processed lyophilized human serum with preservatives after reconstitution.

The IMMULITE 2000 Gastrin Calibration Verification Material (CVM) contains one set of four vials, 2.0 mL each after reconstitution. CVM1 contains a lyophilized processed buffered human protein matrix with preservatives. CVM2, CVM3 and CVM4 contain various levels of synthetic-human gastrin in a lyophilized processed buffered human protein matrix with preservatives.

AI/ML Overview

This document describes the acceptance criteria and performance testing for three In Vitro Diagnostic (IVD) calibration verification materials: IMMULITE® 2000 LH CVM, IMMULITE® 2000 Free T3 CVM, and IMMULITE® 2000 Gastrin CVM. The study proving the devices meet acceptance criteria is the Stability Study.

Due to the nature of these devices (Quality Control Materials), the typical AI/human comparative effectiveness studies, expert consensus for ground truth, or distinct training/test sets are not applicable as they are for diagnostic algorithms. Instead, the performance is evaluated by ensuring the material's dose values remain within specified acceptable ranges over time and under various conditions, determined by the instrument's calibrated reference curve.

The following information focuses on the LH CVM, Free T3 CVM, and Gastrin CVM separately, as each has its own specific acceptance criteria and performance data.

IMMULITE® 2000 LH Calibration Verification Material (CVM)

1. Table of Acceptance Criteria and Reported Device Performance

The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim.

CVM level	Assigned Dose (mIU/mL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (mIU/mL)	Reported Performance (Implied by meeting criteria)
LLHCVM1	0.00	Not Applicable	≤ 0.1	Likely met ≤ 0.1 mIU/mL
LLHCVM2	1.28	±18%	1.05 - 1.51	Likely fell within 1.05 - 1.51 mIU/mL
LLHCVM3	47.2	±12%	41.5 – 52.9	Likely fell within 41.5 – 52.9 mIU/mL
LLHCVM4	190	±14%	163 – 217	Likely fell within 163 – 217 mIU/mL

Note: The document states the tests were performed to demonstrate the device meets performance specifications, and concludes substantial equivalence, implying the acceptance criteria were met. Specific numerical results for each time point are not provided in this summary.

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

Real-time shelf life stability: Not explicitly stated as a "test set" in the traditional sense, but the stability CVMs and reference CVMs were run in duplicate (as a minimum) at time points: 0, 72, 84, and 109 months.
Open Component testing: LH CVM lot 090 was tested at 2-hourly intervals for up to 9 hours.
Data Provenance: Not explicitly stated, but implied to be from internal laboratory testing at Siemens Healthcare Diagnostics Inc. (Tarrytown, NY, USA). This is a prospective test to determine the stability of newly manufactured CVMs.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):

Not applicable in the context of IVD calibration verification materials. Ground truth for dose values is established through traceability to international reference standards (WHO 1st IRP 68/40 and 2nd IS 80/552) and internal reference calibrators.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not applicable. Results are compared against pre-defined numerical acceptance ranges.

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 not an AI-assisted diagnostic device.

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

Not applicable. This is a chemical reagent product used in an automated analyzer. Its performance is inherent to its chemical stability and manufacturing consistency in relation to the instrument's operation.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

The ground truth for the assigned dose values of the CVMs is established through traceability to WHO 1st IRP 68/40 and 2nd IS 80/552 via assigned reference calibrators. This falls under the category of reference standards.

8. The sample size for the training set:

Not applicable. This is a stability study for a calibration verification material, not a machine learning model.

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

Not applicable.

IMMULITE® 2000 Free T3 Calibration Verification Material (CVM) Summary

1. Table of Acceptance Criteria and Reported Device Performance

The stability study was conducted to validate shelf life claims.

CVM level	Assigned Dose (pg/dL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (pg/dL)	Reported Performance (Implied by meeting criteria)
LFT3CVM1	0.00	N/A	≤ 1.00	Likely met ≤ 1.00 pg/dL
LFT3CVM2	1.48	±25%	1.11 – 1.85	Likely fell within 1.11 – 1.85 pg/dL
LFT3CVM3	7.30	±10%	6.57 – 8.03	Likely fell within 6.57 – 8.03 pg/dL
LFT3CVM4	44.5	±15%	37.8 – 51.2	Likely fell within 37.8 – 51.2 pg/dL

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

Real-time shelf life stability: Stability CVMs and reference CVMs were run in duplicate (as a minimum) at time points: 0, 6, 12, and 18 months.
Data Provenance: Not explicitly stated, but implied to be from internal laboratory testing at Siemens Healthcare Diagnostics Inc. (Tarrytown, NY, USA). This is a prospective test to determine the stability of newly manufactured CVMs.

3-6. Not applicable (same reasons as for LH CVM).

7. The type of ground truth used:

The ground truth for the assigned dose values of the CVMs is established through traceability to an internal material which has been gravimetrically prepared. This acts as a reference standard.

8-9. Not applicable.

IMMULITE® 2000 Gastrin Calibration Verification Material (CVM) Summary

1. Table of Acceptance Criteria and Reported Device Performance

The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim.

CVM level	Assigned Dose (pg/mL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (pg/mL)	Reported Performance (Implied by meeting criteria)
LGACVM1	0.00	N/A	< 10.0	Likely met < 10.0 pg/mL
LGACVM2	27.1	±12%	23.9 – 30.4	Likely fell within 23.9 – 30.4 pg/mL
LGACVM3	409	±8%	376 - 442	Likely fell within 376 - 442 pg/mL
LGACVM4	1244	±12%	1095 - 1393	Likely fell within 1095 - 1393 pg/mL

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

Real-time shelf life stability: Stability CVMs and reference CVMs were run in duplicate (as a minimum) at time points: 0, 6, 12, and 18 months.
Open Component testing: CVM 090 was tested at 2-hourly intervals for up to 9 hours.
Data Provenance: Not explicitly stated, but implied to be from internal laboratory testing at Siemens Healthcare Diagnostics Inc. (Tarrytown, NY, USA). This is a prospective test to determine the stability of newly manufactured CVMs.

3-6. Not applicable (same reasons as for LH CVM).

7. The type of ground truth used:

The ground truth for the assigned dose values of the CVMs is established through traceability to Medical Research Council Research Standard A for gastrin II, porcine (NIBSC 66/138). This falls under the category of reference standards.

8-9. Not applicable.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 October 29, 2014

SIEMENS HEALTHCARE DIAGNOSTICS INC. ASHA GARTLAND TECHNICAL REGULATORY AFFAIRS SPECIALIST 511 BENEDICT AVENUE TARRYTOWN NY 10591

Re: K142811

Trade/Device Name: Immulite® 2000 LH Calibration Verification Material (CVM), Immulite® 2000 Free T3 Calibration Verification Material (CVM), Immulite® 2000 Gastrin Calibration Verification Material (CVM) Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I, reserved Product Code: JJX Dated: September 26, 2014 Received: September 29, 2014

Dear Ms. 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 misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

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

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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" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

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

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

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

Sincerely yours,

Courtney

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

Enclosure

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Indications for Use

510(k) Number (if known) K142811

Device Name

IMMULITE® 2000 LH Calibration Verification Material (CVM) IMMULITE® 2000 Free T3 Calibration Verification Material (CVM) IMMULITE® 2000 Gastrin Calibration Verification Material (CVM)

Indications for Use (Describe)

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

The IMMULITE® 2000 Free T3 Calbration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Free T3 assay on the IMMULITE 2000 systems

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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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: K142811

1. Submitter 511 Benedict Avenue Mailing Address: 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:

Predicate Device Name

Predicate 510(k) No:

Device Description:

Siemens Healthcare Diagnostics Inc.

Asha Gartland Technical Regulatory Affairs Specialist (914)-524-3257 (914)-524-2101 asha.gartland@siemens.com October 28th 2014

IMMULITE® 2000 LH Calibration Verification Material Quality Control materials for IMMULITE® 2000 LH assay Calibration Verification Material (CVM) for IMMULITE® 2000 LH assay

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

IMMULITE® 2000 Intact PTH Calibration Verification Material (CVM) K140258

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1. Intended Use: Indication for Use:
  Special Conditions for Use Statement(s): Special Instrument Requirements:
1. Technological Characteristics and Substantial Equivalence Comparison with Predicate:
  See Indications for Use Statement below: The IMMULITE® 2000 LH Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE LH assay on the IMMULITE 2000 systems.

For prescription use only

IMMULITE® 2000 Systems

A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 LH 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 LH CVM	Predicate DeviceIMMULITE 2000 Intact PTH CVM
IntendedUse	The IMMULITE® 2000 LHCalibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE LH assay on theIMMULITE 2000 systems.	The IMMULITE® Intact PTHCalibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE Intact PTH assay onthe IMMULITE 2000 systems.
Form	Lyophilized	Same
Stability	Stable unopened until the expirationdate	Same
Levels	4	Same
Use	Single Use Only	Same

	DIFFERENCES
	Candidate DeviceIMMULITE 2000 LH CVM	Predicate DeviceIMMULITE 2000 Intact PTHCVM
Analyte	LH	Intact PTH
Storage	2 -8 °C	≤-20°C
Matrix	Bovine serum with preservatives	Buffered bovine protein withpreservatives

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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 intended use. The following tests were performed on the candidate device.

7.1 Stability Summary:

The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 LH Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after reconstitution.

The IMMULITE® 2000 LH Calibration Verification Materials are stable up to 9 years when stored at 2-8°C prior to opening and for 8 hours at ambient or room temperature (15-25°C) after reconstitution.

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
LLHCVM1	72	84	109
LLHCVM2	72	84	109
LLHCVM3	72	84	109
LLHCVM4	72	84	109

Table 2: Stability Time Points

For Open Component testing, the results are determined from a 2-point adjustment. Using IMMULITE 2000 LH (L2KLH2) kit lot 305, LH CVM lot 090 was tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions and compared to the determinations at time zero.

7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE LH criteria requires dose value of stability calibrator/CVM to fall between ±18% of assigned dose for CVM level 2, ±12% for CVM level 3 and 14% for CVM level 4.

.The acceptance criterion is summarized in Table 3.

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CVM level	Assigned Dose (mIU/mL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (mIU/mL)
LLHCVM1	0.00	Not Applicable	≤ 0.1
LLHCVM2	1.28	±18%	1.05 - 1.51
LLHCVM3	47.2	±12%	41.5 – 52.9
LLHCVM4	190	±14%	163 – 217

Table 3 Acceptance criteria for stability of IMMULITE 2000 LH CVM

7.2 Traceability:

The IMMULITE LH is traceable to WHO 1st IRP 68/40 and 2nd IS 80/552. The CVMs are manufactured using qualified materials and measurement procedures.

7.3 Value Assignment:

IMMULITE 2000 LH CVMs are 4 level materials which are a subset of 13 level LH calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of LH 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 LH antigen stock and are traceable to WHO 1st IRP 68/40 and 2nd IS 80/552. Six levels of commercially available controls and 5 normal and 25 patient samples were used to validate calibrator/CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The IMMULITE LH calibrators/CVMs were tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, 7 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 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 controls must fall within their target ranges.

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7.4 Expected Values/Reference Range:

Each CVM level was tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, 7 IMMULITE 2000 systems and 4 different reagent kit lots. 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 up to 200 mIU/mL. The target values in Table 4 can be considered as guidelines.

Analytetarget levels	CVM Level	*TargetMean( mIU/mL)	StandardDeviation(SD)	Guideline ±2SD Range( mIU/mL )
	LLHCVM1	0.00	-	0.00	≤0.1
	LLHCVM2	1.71	0.155	1.40	2.02
	LLHCVM3	51.5	3.1	45.3	57.7
	LLHCVM4	202	14.0	174	230
Assay Range	Up to 200 mIU/mL

Table 4: Target 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

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Proposed Labeling:

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

Conclusion: 8.

The IMMULITE® 2000 LH Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 Intact PTH Calibration Verification Material. 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 LH 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: K142811

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 28th, 2014
2. Device Name
Proprietary Name:	IMMULITE® 2000 Free T3 Calibration Verification Material
Measurand:	Quality Control material for IMMULITE® 2000 Free T3 assay
Type of Test:	Calibration Verification Material (CVM) for IMMULITE® 2000Free T3 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
Predicate 510(k) No:	IMMULITE® 2000 HCG Calibration Verification Material (CVM)K133128
4. Device Description:	IMMULITE® 2000 Free T3 Calibration Verification Material (CVM)contains one set of four vials. CVM1 contains 4.0 mL processedlyophilized human serum with preservatives after reconstitution.CVM2, CVM3 and CVM4 contain 2.0mL/vial of various levels of3,31 Triiodo-L-Thyronine (Free Acid) in processed lyophilizedhuman serum with preservatives after reconstitution.
5. Intended Use:Indication for Use:	See Indications for Use Statement belowThe IMMULITE® 2000 Free T3 Calibration Verification Material(CVM) is for in vitro diagnostic use in the verification of calibrationof the IMMULITE Free T3 assay on the IMMULITE 2000 systems.
Special Conditions forUse Statement(s):	For prescription use only
Special InstrumentRequirements:	IMMULITE® 2000 Systems
6. TechnologicalCharacteristics andSubstantial EquivalenceComparison with Predicate:	A comparison of the device features, intended use, and otherinformation demonstrates that the IMMULITE® Free T3 CalibrationVerification Material (CVM) is substantially equivalent to thepredicate device as summarized in Table 1.

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Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate DeviceIMMULITE 2000Free T3 CVM	Predicate DeviceIMMULITE 2000 HCG CVM
IntendedUse	The IMMULITE® 2000 Free T3Calibration Verification Material (CVM) isfor in vitro diagnostic use in the verificationof calibration of the IMMULITE Free T3assay on the IMMULITE 2000 systems	The IMMULITE® HCGCalibration Verification Material(CVM) is for in vitro diagnostic usein the verification of calibration ofthe IMMULITE HCG assay on theIMMULITE 2000 systems
Storage	≤-20°C	Same
Stability	Stable unopened until the expiration date	Same
Levels	4	Same
Use	Single Use Only	Same
Matrix	Human serum with preservatives	Same

DIFFERENCES
	Candidate DeviceFree T3 CVM	Predicate DeviceIMMULITE 2000 HCG CVM
Analyte	Free T3	HCG
Form	Lyophilized	Liquid

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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 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 Free T3 Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after reconstitution.

The IMMULITE 2000 Free T3 Calibration Verification Materials are stable up to 1.5 years when stored at -20°C prior to reconstitution.

7.1.1 Stability Protocol Summary:

CVM Level
LFT3CVM1	6	12	18
LFT3CVM2	6	12	18
LFT3CVM3	6	12	18
LFT3CVM4	6	12	18

Table 2: Stability Time Points

7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Free T3 criteria requires dose value of stability calibrator/CVM to fall between ±25% of assigned dose for CVM level 2, ±10% for CVM level 3 and 15% for CVM level 4.

The acceptance criterion is summarized in Table 3.

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Table 3 Acceptance criteria for stability of IMMULITE 2000 Free T3 CVM

CVM level	AssignedDose(pg/dL)	GuidelineCriteria% difference toassigned dose	Acceptabledose range(pg/dL)
LFT3CVM1	0.00	N/A	≤ 1.00
LFT3CVM2	1.48	±25%	1.11 – 1.85
LFT3CVM3	7.30	±10%	6.57 – 8.03
LFT3CVM4	44.5	±15%	37.8 – 51.2

7.2 Traceability:

The IMMULITE 2000 Free T3 CVMs are traceable to an internal material which has been gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.

7.3 Value Assignment:

The IMMULITE 2000 Free T3 CVMs are 4 level materials which are a subset of 6 level Free T3 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Free T3 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 Free T3 antigen stock and are traceable to an internal material which has been gravimetrically prepared. Six levels of commercially available controls and 30 normal patient samples were used to validate calibrator/CVM value assignments.

The calibrators/CVMs are manufactured using qualified materials and measurement procedures. The calibrators/CVMs were tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, 4 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 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.

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7.4 Expected Values/Reference Range:

Each CVM level was on 15 replicates in total, comprised of 5 runs, 3 replicates per run, 4 IMMULITE 2000 systems and 3 different reagent kit lots. 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 Free T3 CVM Calibration Verification Material lot-specific package insert. *

The expected assay range is 1.0 to 40 pg/mL. The target values in Table 4 can be considered as guidelines.

Analytetarget levels	CVM Level	**TargetMean(pg/mL)	StandardDeviation(SD)	Guideline ±2SD Range(pg/mL)
	LF3CVM1	0.00	-	≤1.00
	LF3CVM2	1.48	0.185	1.85
	LF3CVM3	7.30	0.5475	8.40
	LF3CVM4*	44.5	-	-
	*90% LF3CVM4 +10% LF3CVM1	40.1	3.00	46.1
Assay Range	1.0 to 40 pg/mL

Table 4: Target Values

Note:

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

** 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.

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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

8. Conclusion:

The IMMULITE® 2000 Free T3 Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 HCG Calibration Verification Material. 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 T3 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

1. Submitter
Mailing Address:	Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591
Contact Person:	Asha GartlandTechnical Regulatory Affairs Specialist
Phone Number:	(914)-524-3257
Fax Number:	(914)-524-2101
E-mail Address:	asha.gartland@siemens.com
Date Prepared:	October 28th, 2014
2. Device Name
Proprietary Name:	IMMULITE® 2000 Gastrin Calibration Verification Material
Measurand:	Quality Control materials for IMMULITE® 2000 Gastrin assay
Type of Test:	Calibration Verification Material (CVM) for IMMULITE® 2000Gastrin assay
Regulation Section:	21 CFR 862.1660, Quality Control Material
Classification:	Class I Reserved
Products Code:	JJX – Single (Specified) Analyte Controls (Assayed andUnassayed)
Panel:	Clinical Chemistry (75)
3. Predicate Device Name	IMMULITE® 2000 DHEA-SO4 Calibration Verification Material(CVM)
Predicate 510(k) No:	K140258
4. Device Description:	The IMMULITE 2000 Gastrin Calibration Verification Material(CVM) contains one set of four vials, 2.0 mL each afterreconstitution. CVM1 contains a lyophilized processed bufferedhuman protein matrix with preservatives. CVM2, CVM3 andCVM4 contain various levels of synthetic-human gastrin in alyophilized processed buffered human protein matrix withpreservatives.
5. Intended Use:	See Indications for Use Statement below
Indication for Use:	The IMMULITE® 2000 Gastrin Calibration Verification Material(CVM) is for in vitro diagnostic use in the verification ofcalibration of the IMMULITE Gastrin assay on the IMMULITE2000 systems
Special Conditions forUse Statement(s):Special InstrumentRequirements:	For prescription use onlyIMMULITE® 2000 Systems
6. Technological Characteristicsand Substantial EquivalenceComparison with Predicate:	A comparison of the device features, intended use, and otherinformation demonstrates that the IMMULITE® 2000 GastrinCalibration Verification Material (CVM) is substantially equivalentto the predicate device as summarized in Table 1.

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SIMILARITIES
	Candidate DeviceIMMULITE 2000 Gastrin CVM	Predicate DeviceIMMULITE 2000 DHEA-SO4 CVM
IntendedUse	The IMMULITE® 2000 GastrinCalibration Verification Material (CVM)is for in vitro diagnostic use in theverification of calibration of theIMMULITE Gastrin assay on theIMMULITE 2000 systems	The IMMULITE® DHEA-SO4Calibration Verification Material(CVM) is for in vitro diagnostic use inthe verification of calibration of theIMMULITE DHEA-SO4 assay on theIMMULITE 2000 systems
Form	Lyophilized	Same
Levels	4	Same
Stability	Stable unopened until the expiration date	Same
Storage	≤-20°C	Same
Use	Single Use Only	Same

	IMMULITE Gastrin assay on theIMMULITE 2000 systems	IMMULITE DHEA-SO4 assay on theIMMULITE 2000 systems
Form	Lyophilized	Same
Levels	4	Same
Stability	Stable unopened until the expiration date	Same
Storage	≤-20°C	Same
Use	Single Use Only	Same
DIFFERENCES

DIFFERENCES
	Candidate DeviceIMMULITE 2000 Gastrin CVM	Predicate DeviceIMMULITE 2000 DHEA-SO4 CVM
Analyte	Gastrin	DHEA-SO4
Matrix	Buffered human protein withpreservatives	Human serum with preservatives

Table 1: Substantial Equivalence Comparison

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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 intended use. The following tests were performed on the candidate device.

7.1 Stability Summary:

The stability study was conducted to validate real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Gastrin Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM, before and after reconstitution.

The IMMULITE 2000 Gastrin Calibration Verification Materials are stable up to 1.5 years when stored at ≤ -20°C prior to opening and for 8 hours at ambient or room temperature (15-25°C) after reconstitution.

7.1.1 Stability Protocol Summary:

CVM Level
LGACVM1	6	12	18
LGACVM2	6	12	18
LGACVM3	6	12	18
LGACVM4	6	12	18

Table 2: Stability Time Points

For Open Component testing, the results are determined from a 2-point adjustment. Using IMMULITE 2000 Gastrin kit (L2KGA2) lot 229, CVM 090 was tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE 2000 Gastrin criteria requires dose value of stability calibrator/CVMs to fall between ±12% of assigned dose for CVM level 2, ±8% for CVM level 3 and 12% for CVM level 4.

The acceptance criterion is summarized in Table 3.

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CVM level	Assigned Dose(pg/mL)	Guideline Criteria% difference toassigned dose	Acceptable doserange (pg/mL)
LGACVM1	0.00	N/A	< 10.0
LGACVM2	27.1	±12%	23.9 – 30.4
LGACVM3	409	±8%	376 - 442
LGACVM4	1244	±12%	1095 - 1393

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

For Open Component stability testing the acceptance criteria are the same as guideline criteria described above and in Table 3.

7.2 Traceability:

The IMMULITE 2000 Gastrin CVMs are traceable to Medical Research Council Research Standard A for gastrin II, porcine (NIBSC 66/138). The CVMs are manufactured using qualified materials and measurement procedures.

7.3 Value Assignment:

The IMMULITE 2000 Gastrin CVMs are 4 level materials which are a subset of 10 level Gastrin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Gastrin 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 Gastrin antigen stock and are traceable to Medical Research Council Research Standard A for gastrin II, porcine (NIBSC 66/138). Four levels of commercially available controls and 49 spiked serum samples and 5 normal serum samples were 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, 3 replicates per run, 9 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. 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.

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7.4 Expected Values/Reference Range:

Each CVM level was tested tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, 9 IMMULITE 2000 systems and 3 different reagent kit lots. 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 Gastrin CVM Calibration Verification Material lot-specific package insert. *

The expected assay range is up to 1000 pg/mL. The target values in Table 4 can be considered as guidelines.

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

Analytetarget levels	CVM Level	**TargetMean(pg/mL)	StandardDeviation(SD)	Guideline ±2SD Range(pg/mL)
	LGACVM1	0.00	-	≤10
	LGACVM2	25.8	2.0	21.9	29.7
	LGACVM3	367	24	319	415
	LGACVM4*	1183	-	-	-
	*85% LGACVM4 +15% LGACVM1	1006	80.5	845	1167
Assay Range	Up to 1000 pg/mL

Note

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

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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

8. Conclusion:

The IMMULITE® 2000 Gastrin Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 DHEA-SO4 Calibration Verification Material 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 Gastrin Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

Regulation Number and Section

§ 862.1660 Quality control material (assayed and unassayed).

(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.