K Number

Device Name

IMMULITE 2000; TOTAL T3 CALIBRATION VERIFICATION MATERIAL, TOTAL T4 CALIBRATION VERIFICATION MATERIAL, TOTAL TBG CALIBRA

Manufacturer

Siemens Healthcare Diagnostics Inc.

Date Cleared

2013-10-25

(25 days)

Product Code

JJX

Regulation Number

862.1660

Intended Use

The IMMULITE® Total T3 Calibration Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Total T3 assay on the IMMULITE 2000 systems. The IMMULITE® Total T4 Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Total T4 assay on the IMMULITE 2000 systems. The IMMULITE® TBG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE TBG assay on the IMMULITE 2000 systems. The IMMULITE® FSH Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE FSH assay on the IMMULITE 2000 systems. The IMMULITE® Estradiol Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Estradiol assay on the IMMULITE 2000 systems.

Device Description

IMMULITE® 2000 Total T3 Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. LT3CVM1 contains T3-free human serum matrix with preservatives. LT3CVM2, LT3CVM3 and LT3CVM4 contain low, intermediate and high levels of T3 respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form. IMMULITE® 2000 Total T4 Calibration Verification. Material (CVM) contains one set of four vials, 3 mL each. LT4CVM1 contains T4-free human serum matrix with preservatives. LT4CVM2, LT4CVM3 and LT4CVM4 contain low, intermediate and high levels of T4 respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form. IMMULITE® 2000 TBG Calibration Verification Material (CVM) contains one set of four vials, 2.0 mL each. LTBCVM1 contains a bovine-based matrix with preservatives. LTBCVM2, LTBCVM3 and LTBCVM4 contain low, intermediate and high levels of TBG respectively, in human-based matrix with preservatives. CVMs are supplied frozen in lyophilized form. IMMULITE® 2000 FSH Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. LFSCVM1 contains a bovine serum with preservatives. LFSCVM2. LFSCVM3 and LFSCVM4, 2 mL each, contain low, intermediate and high levels of human source FSH respectively, in bovine serum matrix with preservatives. CVMs are supplied frozen in lyophilized form. IMMULITE® 2000 Estradiol Calibration Verification Material (CVM) contains one set of four vials. 2 mL each. LE2CVM1 contains human serum with preservatives. LE2CVM2. LE2CVM3 and LE2CVM4 contain low, intermediate and high levels of human source Estradiol respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K111552,K112528,K020217,K964829,K102904

Reference Devices

K111552,K112528,K020217,K964829,K102904

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes calibration verification materials for in vitro diagnostic assays and their performance testing, with no mention of AI or ML technologies.

Therapeutic

No.
Explanation: The device is a "Calibration Verification Material" used for in vitro diagnostic purposes to verify the calibration of assays on IMMULITE 2000 systems. It is not intended for treating or diagnosing medical conditions, but rather for ensuring the accuracy of laboratory equipment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the calibration verification materials are "intended for in vitro diagnostic use."

SaMD (Software as a Medical Device)

The device description clearly states that the device is a physical material (lyophilized human/bovine serum matrix with analytes and preservatives) supplied in vials, intended for in vitro diagnostic use. It is not software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The document explicitly states that the IMMULITE® Calibration Verification Materials are "intended for in vitro diagnostic use". This is the primary indicator.
Purpose: The materials are used to verify the calibration of diagnostic assays (IMMULITE Total T3, Total T4, TBG, FSH, and Estradiol assays) performed on the IMMULITE 2000 systems. These assays are used to measure analytes in biological samples (human serum) to aid in diagnosis or monitoring of medical conditions.
Device Description: The materials are composed of human serum matrix with specific analytes at different concentrations, designed to mimic patient samples for the purpose of calibration verification.
Intended User/Care Setting: It is stated "For in vitro diagnostic use" and "For prescription use only", indicating use in a clinical laboratory setting.

While the performance studies focus on the stability and value assignment of the calibration verification materials themselves, rather than diagnostic accuracy metrics like sensitivity or specificity, their intended purpose is to ensure the accuracy of diagnostic tests. Therefore, they fall under the definition of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The IMMULITE® Total T3 Calibration Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Total T3 assay on the IMMULITE 2000 systems.

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

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

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

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

Product codes

JJX

Device Description

IMMULITE® 2000 Total T3 Calibration Verification Material: The Total T3 Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. LT3CVM1 contains T3-free human serum matrix with preservatives. LT3CVM2, LT3CVM3 and LT3CVM4 contain low, intermediate and high levels of T3 respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

IMMULITE® 2000 Total T4 Calibration Verification Material: IMMULITE® 2000 Total T4 Calibration Verification. Material (CVM) contains one set of four vials, 3 mL each. LT4CVM1 contains T4-free human serum matrix with preservatives. LT4CVM2, LT4CVM3 and LT4CVM4 contain low, intermediate and high levels of T4 respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

IMMULITE® 2000 TBG Calibration Verification Material: IMMULITE® 2000 TBG Calibration Verification Material (CVM) contains one set of four vials, 2.0 mL each. LTBCVM1 contains a bovine-based matrix with preservatives. LTBCVM2, LTBCVM3 and LTBCVM4 contain low, intermediate and high levels of TBG respectively, in human-based matrix with preservatives. CVMs are supplied frozen in lyophilized form.

IMMULITE® 2000 FSH Calibration Verification Material: IMMULITE® 2000 FSH Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. LFSCVM1 contains a bovine serum with preservatives. LFSCVM2. LFSCVM3 and LFSCVM4, 2 mL each, contain low, intermediate and high levels of human source FSH respectively, in bovine serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

IMMULITE® 2000 Estradiol Calibration Verification Material: IMMULITE® 2000 Estradiol Calibration Verification Material (CVM) contains one set of four vials. 2 mL each. LE2CVM1 contains human serum with preservatives. LE2CVM2. LE2CVM3 and LE2CVM4 contain low, intermediate and high levels of human source Estradiol respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

For prescription use only

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Non-Clinical Performance Testing - Stability Study:

IMMULITE® 2000 Total T3 Calibration Verification Material: Stable up to 5 years when stored frozen at -20°C prior to opening. The IMMULITE Total T3 CVMs are traceable to internal assigned reference calibrators prepared using Total T3 antigen stock solution and are traceable to internal material which is gravis protecally prepared. Values are assigned using assigned reference calibrators with recovery of patient samples and controls performed for quality control. Expected range: 40-600 ng/dL.
IMMULITE® 2000 Total T4 Calibration Verification Material: Stable up to 3.5 years when stored frozen at -20°C prior to opening. The IMMULITE Total T4 CVMs are traceable to internal assigned reference calibrators prepared using Total T4 antigen stock solution and are traceable to internal material which is gravimetrically prepared. Values are assigned using assigned reference calibrators with recovery of patient samples and controls performed for quality control. Expected range: 1.0 -24 µg/dL.
IMMULITE® 2000 TBG Calibration Verification Material: Stable up to 5 years when stored frozen at -20℃ prior to opening. The IMMULITE TBG CVMs are traceable to WHO 1ST International Standard 88/638. Values are assigned using assigned reference calibrators with recovery of patient samples and controls performed for quality control. Expected range: 3.5-80 µg/mL.
IMMULITE® 2000 FSH Calibration Verification Material: Stable up to 5 years when stored frozen at -20°C prior to opening. The IMMULITE FSH CVMs are traceable to WHO 2nd IRP (78/549, interim replacement code 94/632). Values are assigned using assigned reference calibrators with recovery of patient samples and controls performed for quality control. Expected range: 0.1 -170 mIU/mL.
IMMULITE® 2000 Estradiol Calibration Verification Material: Stable up to 5 years when stored frozen at -20℃ prior to opening. The IMMULITE Estradiol CVMs are traceable to internal assigned reference calibrators prepared using an Estradiol antigen stock solution and are traceable to internal material which is gravimetrically prepared. Values are assigned using assigned reference calibrators with recovery of patient samples and controls performed for quality control. Expected range: 20 -2000 pg/mL.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

IMMULITE® 2000 Total T3 Calibration Verification Material:

Acceptance Criteria for Stability:
- LT3CVM1: ≤40.00 ng/dL
- LT3CVM2: 88.88 - 113.12 ng/dL (±12% difference to assigned dose of 101 ng/dL)
- LT3CVM3: 197.8 - 232.2 ng/dL (±8% difference to assigned dose of 215 ng/dL)
- LT3CVM4: 518.5 - 701.5 ng/dL (±15% difference to assigned dose of 610 ng/dL)
- Review Limits: Controls are within 2SD of target from stability calibrator curve.
Target Mean and Guideline ±2SD Range for Analyte Target Levels:
- LT3CVM1: Target Mean 0.00, Guideline ≤40.00 ng/dL
- LT3CVM2: Target Mean 99.0, Guideline 87.1 - 111 ng/dL
- LT3CVM3: Target Mean 201, Guideline 173 - 229 ng/dL
- LT3CVM4: Target Mean 603, Guideline 513 - 693 ng/dL

IMMULITE® 2000 Total T4 Calibration Verification Material:

Acceptance Criteria for Stability:
- LT4CVM1: ≤1.00 µg/dL (not applicable for guideline criteria)
- LT4CVM2: 3.44 - 4.20 µg/dL (±10% difference to assigned dose of 3.82 µg/dL)
- LT4CVM3: 14.22 - 17.38 µg/dL (±10% difference to assigned dose of 15.80 µg/dL)
- LT4CVM4: 22.50 - 27.50 µg/dL (±10% difference to assigned dose of 25.00 µg/dL)
- Review Limits: Controls are within 2SD of target from stability calibrator curve.
Target Mean and Guideline ±2SD Range for Analyte Target Levels:
- LT4CVM1: Target Mean 0.00, Guideline 0.00 ≤1.00 µg/dL
- LT4CVM2: Target Mean 3.87, Guideline 3.21-4.53 µg/dL
- LT4CVM3: Target Mean 16.0, Guideline 14.1-17.9 µg/dL
- LT4CVM4: Target Mean 25.0, Guideline 22.3-27.8 µg/dL

IMMULITE® 2000 TBG Calibration Verification Material:

Acceptance Criteria for Stability:
- LTBCVM1: ≤3.50 µg/mL (not applicable for guideline criteria)
- LTBCVM2: 4.48 - 6.72 µg/mL (±20% difference to assigned dose of 5.60 µg/mL)
- LTBCVM3: 43.35 - 58.65 µg/mL (±15% difference to assigned dose of 51.0 µg/mL)
- LTBCVM4: 79.60-119.40 µg/mL (±20% difference to assigned dose of 99.5 µg/mL)
- Review Limits: Controls are within 2SD of target from stability calibrator curve.
Target Mean and Guideline ±2SD Range for Analyte Target Levels:
- LTBCMV1: Target Mean 0.00, Guideline 0.00 ≤3.50 µg/mL
- LTBCVM2: Target Mean 5.85, Guideline 4.68-7.02 µg/mL
- LTBCVM3: Target Mean 49.9, Guideline 42.4-57.4 µg/mL
- LTBCVM4: Target Mean 99.0 (85% of LTBCVM4 + 15% of LTB1CVM1)*, Guideline 67.4-101 µg/mL

IMMULITE® 2000 FSH Calibration Verification Material:

Acceptance Criteria for Stability:
- LFSCVM1: ≤0.10 mIU/mL (not applicable for guideline criteria)
- LFSCVM2: 4.18 - 5.10 mIU/mL (±10% difference to assigned dose of 4.64 mIU/mL)
- LFSCVM3: 86.40 - 105.60 mIU/mL (±10% difference to assigned dose of 96 mIU/mL)
- LFSCVM4: 156.60 - 191.40 mIU/mL (±10% difference to assigned dose of 174 mIU/mL)
- Review Limits: Controls are within 2SD of target on each curve.
Target Mean and Guideline ±2SD Range for Analyte Target Levels:
- LFSCVM1: Target Mean 0.00, Guideline 0.00 ≤0.10 mIU/mL
- LFSCVM2: Target Mean 4.59, Guideline 4.13-5.05 mIU/mL
- LFSCVM3: Target Mean 98, Guideline 82.3-114 mIU/mL
- LFSCVM4: Target Mean 174, Guideline 146-202 mIU/mL

IMMULITE® 2000 Estradiol Calibration Verification Material:

Acceptance Criteria for Stability:
- LE2CVM1: ≤20.00 pg/mL (not applicable for guideline criteria)
- LE2CVM2: 44.72 - 59.28 pg/mL (±14% difference to assigned dose of 52 pg/mL)
- LE2CVM3: 451.80 - 552.20 pg/mL (±10% difference to assigned dose of 502 pg/mL)
- LE2CVM4: 2137.16 - 2508.84 pg/mL (±8% difference to assigned dose of 2323 pg/mL)
- Review Limits: Controls are within 2SD of target on each curve.
Target Mean and Guideline ±2SD Range for Analyte Target Levels:
- LE2CVM1: Target Mean 0.00, Guideline ≤20.00 pg/mL
- LE2CVM2: Target Mean 61.5, Guideline 81.20 pg/mL
- LE2CVM3: Target Mean 478, Guideline 545 pg/mL
- LE2CVM4: Target Mean 2034, Guideline 2319 pg/mL

Predicate Device(s)

Elecsys T3 CalCheck 5 K111552, Elecsys T4 CalCheck 5 K112528, ADVIA Centaur® Intact PTH Master Curve Material K020217, Elecsys FSH CalCheck K964829, ADVIA Centaur® Enhanced Estradiol (eE2) MCM K102904

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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.

Summary

SIEMENS

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: K133124

1. Submitter
Mailing Address:	Siemens Healthcare Diagnostics Inc.
511 Benedict Avenue
Tarrytown, NY 10591
Contact Person:	Garo Mimaryan, MS, RAC
Technical Regulatory Affairs Specialist III		OCT 2 5 2013
Phone Number:	(914)-524-3270
Fax Number:	(914)-524-2101
E-mail Address:	garo.mimaryan@siemens.com
Date Prepared:	October 15, 2013
2. Device Name
Proprietary Name:	IMMULITE® 2000 Total T3 Calibration Verification Material
Measurand:	Quality Control materials for IMMULITE® 2000 Total T3 assay
Type of Test:	Calibration Verification Material (CVM) for IMMULITE® 2000
Total 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)

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

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

Elecsys T3 CalCheck 5 K ! 1 1 552

The Total T3 Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. LT3CVM1 contains T3-free human serum matrix with preservatives. LT3CVM2, LT3CVM3 and LT3CVM4 contain low, intermediate and high levels of T3 respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

See Indications for Use Statement below The IMMULITE® Total T3 Calibration Verification Material (CVM): For in vitro diagnostic use in the verification of calibration of the IMMULITE Total T3 assay on the IMMULITE 2000 systems

For prescription use only

IMMULITE® 2000 Systems

1. Technological Characteristics A comparison of the device features, intended use, and other and Substantial Equivalence information demonstrates that the IMMULITE® 2000 Total T3 Comparison with Predicate: Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.

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

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE 2000 Total T3 CVM	Elecsys T3 CalCheck 5
Intended
Use	The IMMULITE® Total T3 Calibration
Verification Material (CVM) is for in vitro
diagnostic use in the verification of
calibration of the IMMULITE Total T3
assay on the IMMULITE 2000 systems	The Elecsys T3 CalCheck 5 is an assayed
control for use in calibration verification
and for use in the verification of the
assay range established by the Elecsys
T3 reagent on the indicated Elecsys and
cobas e immunoassay analyzers.
Analyte	T3	Same
Form	Lyophilized	Same
Matrix	Human Serum	Same
Stability	Stable unopened until the expiration date	Same

DIFFERENCES
	Candidate Device	Predicate Device
	IMMULITE 2000 Total T3 CVM	Elecsys T3 CalCheck 5
Levels	4	5
Storage	-20°C	2-8°C
Use	Single Use Only	Not for Single Use

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 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. The Calibration Verification Materials are stable up to 5 years when stored frozen at -20°C prior to opening.

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) and the dose value determined from the reference calibrator curve and is summarized in Table 2.

Table 2: Stability Protocol Summary

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|------|------|------|
| LT3CVM1 | 1 | 1092 | 1456 | 1820 |
| LT3CVM2 | 1 | 1092 | 1456 | 1820 |
| LT3CVM3 | 1 | 1092 | 1456 | 1820 |
| LT3CVM4 | 1 | 1092 | 1456 | 1820 |

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Total T3 Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the guideline acceptance criteria which require dose value of stability CVM to fall between ±12% of assigned dose for CVM level 2, ±8% of assigned dose for CVM levels 3 and ±15% for CVM level 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±12% for level 2 and ±8% for levels 3 and ±15% for CVM level 4 then additional data review is conducted using part 2 criteria. The acceptance criteria is summarized in Table 3.

| CVM
Level | Assigned Dose
(ng/dL) | Guideline Criteria
% difference to
assigned dose | Acceptable Dose
range (ng/dL) | Review Limits |
|--------------|--------------------------|--------------------------------------------------------|----------------------------------|-------------------------------|
| LT3CVM1 | 0.00 | not applicable | ≤40.00 | Controls are |
| LT3CVM2 | 101 | ±12 | 88.88 - 113.12 | within 2SD of |
| LT3CVM3 | 215 | ±8 | 197.8 - 232.2 | target from |
| LT3CVM4 | 610 | ±15 | 518.5 - 701.5 | stability
calibrator curve |

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

Traceability:

The IMMULITE Total T3 CVMs are traceable to internal assigned reference calibrators prepared using Total T3 antigen stock solution and are traceable to internal material which is gravis protecally prepared.

Value Assignment:

The IMMULITE Total T3 CVMs are 4 level materials which are a subset of 6 level Total T3 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Total 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 Total T3 antigen stock and are traceable to internal material which hass been gravimetrically prepared. 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 ore 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 control using the assigned CVM values. The controls must fall within their target and Two tri-level commercially available controls, and 25 patient samples (5 normal patients samples and 20 patient panel samples) are 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, 6 different reagent kit lots and 8 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 40-600 ng/dL. The target values in Table 4 and be considered as guidelines.

Analyte target levels	CVM Level	Target Mean (ng/dL)	SD	Guideline ±2SD Range (ng/dL)
	LT3CVM1	0.00	-	≤40.00
	LT3CVM2	99.0	5.975	87.1 - 111
	LT3CVM3	201	14	173 - 229
	LT3CVM4	603	45	513 - 693
Assay Range	40 - 600 ng/dL

Table 4: Analyte Target Range Values

Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, than a 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 quidelines. 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

9. Conclusion:

The IMMULITE® 2000 Total T3 Calibration Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently Elecsys T3 CalCheck 5. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence. product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Total T3 Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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: K133124

1. Submitter Mailing Address:
  Siemens Healthcare Diagnostics Inc. 511 Benedict Avenue Tarrytown. NY 10591

Contact Person:

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

Device Name Proprietary Name: Measurand: Type of Test:

Regulation Section: Classification: Products Code:

Panel:

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

Device Descrintion:
Intended Use: Indication for Use:

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

Garo Mimaryan, MS, RAC Technical Regulatory Affairs Specialist III (914)-524-3270 (914)-524-2101

garo.mimaryan@siemens.com October 15, 2013

IMMULITE® 2000 Total T4 Calibration Verification Material Quality Control materials for IMMULITE® 2000 Total T4 assay Calibration Verification Material (CVM) for IMMULITE® 2000 Total T4 assav 21 CFR 862.1660. Quality Control Material Class I Reserved JJX – Single (Specified) Analyte Controls (Assayed and Unassaved) Clinical Chemistry (75)

Elecsys T4 CalCheck 5 K112528

IMMULITE® 2000 Total T4 Calibration Verification. Material (CVM) contains one set of four vials, 3 mL each. LT4CVM1 contains T4-free human serum matrix with preservatives. LT4CVM2, LT4CVM3 and LT4CVM4 contain low, intermediate and high levels of T4 respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

See Indications for Use Statement below The IMMULITE® Total T4 Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Total T4 assay on the IMMULITE 2000 systems

For prescription use only

IMMULITE® 2000 Systems

1. Technological Characteristics A comparison of the device features, intended use, and other and Substantial Equivalence information demonstrates that the IMMULITE® 2000 Total T4 Comparison with Predicate: Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE 2000 Total T4 CVM	Elecsys T4 CalCheck 5
Intended
Use	The IMMULITE® Total T4 Calibration
Verification Material (CVM) is for in vitro
diagnostic use in the verification of
calibration of the IMMULITE Total T4
assay on the IMMULITE 2000 systems	The Elecsys T4 CalCheck 5 is an assayed
control for use in calibration verification
and for use in the verification of the
assay range established by the Elecsys
T4 reagent on the indicated
Elecsys and cobas e immunoassay
analyzers
Analyte	T4	Same
Form	Lyophilized	Same
Matrix	Human Serum	Same
Stability	Stable unopened until the expiration date	Same

Table 1: Substantial Equivalence Comparison

DIFFERENCES
	Candidate Device	Predicate Device
	IMMULITE 2000 Total T4 CVM	Elecsys T4 CalCheck 5
Levels	4	5
Storage	-20°C	2-8°C
Use	Single Use Only	Not for Single Use

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 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 3.5 years when stored frozen at -20°C prior to opening.

Stability Protocol Summary:

The CVMs are run as part of the calibrator stability testing. The stability CVMs and reference CVMs are run in duplicate (as a minimum) and the dose value determined from reference calibrator curve and is summarized in Table 2.

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|-----|------|------|
| LT4CVM1 | 1 | 910 | 1092 | 1274 |
| LT4CVM2 | 1 | 910 | 1092 | 1274 |
| LT4CVM3 | 1 | 910 | 1092 | 1274 |
| LT4CVM4 | 1 | 910 | 1092 | 1274 |

Table 2: Stability Protocol Summary

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Total T4 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. 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 callbrator curve. If the result is not within acceptable dose range of ±10% then additional data review is conducted using part 2 criteria. The acceptance criteria is summarized in Table 3.

Table 3 Acceptance criteria for stability of IMMULITE 2000 Total T4 CVM

| CVM
Level | Assigned Dose
(µg/dL) | Guideline
Criteria %
difference to
assigned dose | Acceptable Dose
range (µg/dL) | Review Limits |
|--------------|--------------------------|-----------------------------------------------------------|----------------------------------|-------------------------------|
| LT4CVM1 | 0.00 | not applicable | ≤1.00 | Controls are |
| LT4CVM2 | 3.82 | ±10 | 3.44 - 4.20 | within 2SD of |
| LT4CVM3 | 15.80 | ±10 | 14.22 - 17.38 | target from |
| LT4CVM4 | 25.00 | ±10 | 22.50 - 27.50 | stability
calibrator curve |

Traceability:

The IMMULITE Total T4 CVMs are traceable to internal assigned reference calibrators prepared using Total T4 antigen stock solution and are traceable to internal material which is gravimetrically prepared.

Value Assignment:

The IMMULITE® 2000 Total T4 CVMs are 4 level materials which are a subset of 6 level Total T4 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Total T4 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 Total T4 antigen stock and are traceable to an internal material which has been gravimetrically prepared. 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. 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 tri-level commercially available controls, and 25 patient samples (5 normal patients samples and 20 patient panel samples) are 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 TOTAL T4 CVMs were tested on 27 replicates in total comprised of 9 runs, 7 IMMULITE 2000 systems and 6 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 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 1.0 -24 ug/dL. The target values in Table 4 can be considered as guidelines.

| Analyte
target levels | CVM Level | Target Mean
(µg/dL) | SD | Guideline ±2SD Range
(µg/dL) |
|--------------------------|-----------|------------------------|-------|---------------------------------|
| | LT4CVM1 | 0.00 | - | 0.00
≤1.00 |
| | LT4CVM2 | 3.87 | 0.33 | 3.21
4.53 |
| | LT4CVM3 | 16.0 | 0.95 | 14.1
17.9 |
| | LT4CVM4 | 25.0 | 1.375 | 22.3
27.8 |

Table 4: Analyte Target Range Levels

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

9. Conclusion:

The Total T4 Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Elecsys T4 CalCheck 5. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device. The IMMULITE® 2000 Total T4 Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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: K133124

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:

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 Technical Regulatory Affairs Specialist III (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com October 15. 2013

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

ADVIA Centaur® Intact PTH Master Curve Material K020217

IMMULITE® 2000 TBG Calibration Verification Material (CVM) contains one set of four vials, 2.0 mL each. LTBCVM1 contains a bovine-based matrix with preservatives. LTBCVM2, LTBCVM3 and LTBCVM4 contain low, intermediate and high levels of TBG respectively, in human-based matrix with preservatives. CVMs are supplied frozen in lyophilized form.

See Indications for Use Statement below

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

For prescription use only

IMMULITE® 2000 Systems

SIEMENS

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

| Table 1: Substantial Equivalence Comparison
CARDE IN COLLECTION COLLEGION COLLEGION COLLEGION

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	--	--	--	--

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE 2000 TBG CVM	ADVIA Centaur Intact PTH MCM
Intended
Use	The IMMULITE® TBG Calibration
Verification Material (CVM) is for in vitro
diagnostic use in the verification of
calibration of the IMMULITE TBG assay
on the IMMULITE 2000 systems	For in vitro diagnostic use for evaluating
the ADVIA Centaur® Intact PTH assays.
This material is intended to be run singly
as unknown samples after a two-point
calibration has been performed on the
system
Form	Lyophilized	Same
Stability	Stable unopened until the expiration date	Same
Storage	-20°C	Same
Use	Single Use Only	Same

DIFFERENCES
	Candidate Device	Predicate Device
	IMMULITE 2000 TBG CVM	ADVIA Centaur Intact PTH Master
Curve Material (MCM)
Analyte	TBG	Intact PTH
Levels	4	7
Matrix	Human Serum	Bovine Serum

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 TBG 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 5 years when stored frozen at -20℃ prior to opening.

Stability Protocol Summary:

Table 2: Stability Protocol Summary

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|------|------|------|
| LTBCVM1 | 1 | 1456 | 1638 | 1820 |
| LTBCVM2 | 1 | 1456 | 1638 | 1820 |
| LTBCVM3 | 1 | 1456 | 1638 | 1820 |
| LTBCVM4 | 1 | 1456 | 1638 | 1820 |

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE TBG 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 ±20% of assigned dose for CVM level 2, ±15% of assigned dose for CVM levels 3 and ±20% 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 ±20% for level 2 and ±15% for levels 3 and ±20% for CVM level 4 then additional data review is conducted using part 2 criteria. The acceptance criteria is summarized in Table 3.

| CVM
Level | Assigned Dose
(µg/mL) | Guideline Criteria %
difference to assigned
dose | Acceptable
Dose range
(µg/mL) | Review Limits |
|--------------|--------------------------|--------------------------------------------------------|-------------------------------------|----------------------|
| LTBCVM1 | 0.00 | not applicable | ≤3.50 | Controls are within |
| LTBCVM2 | 5.60 | ±20 | 4.48 - 6.72 | 2SD of target from |
| LTBCVM3 | 51.0 | ±15 | 43.35 - 58.65 | stability calibrator |
| LTBCVM4 | 99.5 | ±20 | 79.60-119.40 | curve |

Table 3 Acceptance criteria for stability of IMMULITE_2000 TBG CVM

Traceability:

The IMMULITE TBG CVMs are traceable to WHO 1ST International Standard 88/638. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE® 2000 TBG CVMs are 4 level materials which are a subset of 7 level TBG calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of TBG 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. Two levels of commercially available controls, and 30 patient samples (5 spiked normal patients samples and 25 patient panel samples) are 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 TBG CVMs were tested on 15 replicates in total comprised of 5 runs and 3 replicates per run, 4 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 3.5-80 ug/mL. The target values in Table 4 can be considered as guidelines.

| Analyte
target levels | CVM Level | Target Mean
µg/mL | SD | Guideline ±2SD Range
(µg/mL) |
|--------------------------|----------------------------------------|----------------------|-------|---------------------------------|
| | LTBCMV1 | 0.00 | - | 0.00
≤3.50 |
| | LTBCVM2 | 5.85 | 0.585 | 4.68
7.02 |
| | LTBCVM3 | 49.9 | 3.75 | 42.4
57.4 |
| | LTBCVM4 | 99.0 | - | - |
| | (85% of LTBCVM4 +
15% of LTB1CVM1)* | 84.2 | 8.4 | 67.4
101 |
| Assay Range | 3.5 - 80 µg/mL | | | |

Table 4: Analyte Target Range Levels

*Note: LTBCVM4 requires dilution to ensure that the target value is within the +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 Unassaved Quality Control Material .

Proposed Labeling:

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

9. Conclusion:

TBG Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed ADVIA Centaur Intact PTH MCM . 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 TBG Calibration Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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: K133124

1. Submitter Mailing Address:
  Contact Person:

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

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

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

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

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

Garo Mimaryan, MS, RAC Technical Regulatory Affairs Specialist III (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com October 15, 2013

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

Elecsvs FSH CalCheck K964829

IMMULITE® 2000 FSH Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. LFSCVM1 contains a bovine serum with preservatives. LFSCVM2. LFSCVM3 and LFSCVM4, 2 mL each, contain low, intermediate and high levels of human source FSH respectively, in bovine serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

See Indications for Use Statement below

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

For prescription use only IMMULITE® 2000 Systems

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

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE 2000 FSH CVM	Elecsys FSH CalCheck
Intended
Use	The IMMULITE® FSH Calibration
Verification Material (CVM) is for in
vitro diagnostic use in the verification of
calibration of the IMMULITE FSH assay
on the IMMULITE 2000 systems	For use in the verification of the
calibration established by the Elecsys
FSH reagent on the indicated Elecsys
and cobas e immunoassay analyzers.
Analyte	FSH	Same
Form	Lyophilized	Same
Stability	Stable unopened until the expiration date	Same

DIFFERENCES

	Candidate Device	Predicate Device
	IMMULITE 2000 FSH CVM	Elecsys FSH CalCheck
Levels	4	3
Matrix	Bovine Serum	Human Serum
Storage	-20°C	2-8°C
Use	Single Use Only	Not for Single Use

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:

Stability Protocol Summary:

Table 2: Stability Protocol Summary

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|------|------|------|
| LFSCVM1 | 1 | 1460 | 1642 | 1825 |
| LFSCVM2 | 1 | 1460 | 1642 | 1825 |
| LFSCVM3 | 1 | 1460 | 1642 | 1825 |
| LFSCVM4 | 1 | 1460 | 1642 | 1825 |

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE FSH 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. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±10% then additional data review is conducted using part 2 criteria. The acceptance criteria is summarized in Table 3.

Table 3 Acceptance criteria for stability of IMMULITE 2000 FSH CVM

CVM Level	Assigned Dose (mIU/mL)	Guideline Criteria % difference to assigned dose	Acceptable dose range (mIU/mL)	Review Limits
LFSCVM1	0	not applicable	$ \le $ 0.10
LFSCVM2	4.64	$ \pm $ 10	4.18 - 5.10	Controls are within 2SD of
LFSCVM3	96	$ \pm $ 10	86.40 - 105.60	target on each
LFSCVM4	174	$ \pm $ 10	156.60 - 191.40	curve

Traceability:

The IMMULITE FSH CVMs are traceable to WHO 2nd IRP (78/549, interim replacement code 94/632).

Value Assignment:

The IMMULITE® 2000 FSH CVMs are 4 level materials which are a subset of 9 level FSH calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of FSH reagents and two point adjustors. 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 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 FSH CVMs were tested on 15 replicates in total comprised of 5 runs and 3 replicates per run. 5 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 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 0.1 -170 mlU/mL. The target values in Table 4 can be considered as guidelines.

| Analyte
target
levels | CVM Level | Target Mean
(mIU/mL) | SD | Guideline ±2SD Range
(mIU/mL) |
|-----------------------------|------------------|-------------------------|-------|----------------------------------|
| | LFSCVM1 | 0.00 | - | 0.00
≤0.10 |
| | LFSCVM2 | 4.59 | 0.23 | 4.13
5.05 |
| | LFSCVM3 | 98 | 7.925 | 82.3
114 |
| | LFSCVM4 | 174 | 14 | 146
202 |
| Assay
Range | 0.1 - 170 mIU/mL | | | |

Table 4: Analyte Target Range Levels

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 assigninent 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

্ৰ

ﻢ. Conclusion:

The FSH Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed Elecsys FSH CalCheck. 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 FSH Calibration Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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: K133124

1. Submitter Mailing Address:
  Contact Person:

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

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

Predicate Device Name Predicate 510(k) No:

1. 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 Technical Regulatory Affairs Specialist III (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com October 15. 2013

IMMULITE® 2000 Estradio1 Calibration Verification Material Quality Control materials for IMMULITE® 2000 Estradiol assay Calibration Verification Material (CVM) for IMMULITE® 2000 Estradiol assay 21 CFR 862.1660. Quality Control Material Class I Reserved JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) Clinical Chemistry (75)

ADVIA Centaur® Enhanced Estradiol (eE2) MCM K102904

IMMULITE® 2000 Estradiol Calibration Verification Material (CVM) contains one set of four vials. 2 mL each. LE2CVM1 contains human serum with preservatives. LE2CVM2. LE2CVM3 and LE2CVM4 contain low, intermediate and high levels of human source Estradiol respectively, in human serum matrix with preservatives. CVMs are supplied frozen in lyophilized form.

See Indications for Use Statement below

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

For prescription use only IMMULITE® 2000 Systems

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

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate Device	Predicate Device
	IMMULITE 2000 Estradiol CVM	The ADVIA Centaur® Enhanced
Estradiol (eE2) MCM
Intended
Use	The IMMULITE® Estradiol Calibration
Verification Material (CVM) is for in vitro
diagnostic use in the verification of
calibration of the IMMULITE Estradiol
assay on the IMMULITE 2000 systems	The ADVIA Centaur® Enhanced
Estradiol (eE2) Master Curve Material is
for in vitro diagnostic
use in the verification of calibration and
reportable range of the ADVIA Centaur
Enhanced Estradiol assay.
Analyte	Estradiol.	Same
Form	Lyophilized	Same
Matrix	Human Serum	Same
Stability	Stable unopened until the expiration date	Same
Use	Single Use Only	Same

DIFFERENCES

	Candidate Device	Predicate Device
	IMMULITE 2000 Estradiol CVM	The ADVIA Centaur® Enhanced
Estradiol (eE2) MCM
Levels	4	6
Storage	-20°C	2-8°C

7. Non-Clinical Performance Testing

Performance testing has been carried out to demonstrate that this device meets the performance specifications for its 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 Estradiol 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 CVM. The Clibration Verification Materials are stable up to 5 years when stored frozen at -20℃ prior to opening.

Stability Protocol Summary:

Table 2: Stability Protocol Summarv

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|------|------|------|
| LE2CVM1 | 1 | 1460 | 1642 | 1825 |
| LE2CVM2 | 1 | 1460 | 1642 | 1825 |
| LE2CVM3 | 1 | 1460 | 1642 | 1825 |
| LE2CVM4 | 1 | 1460 | 1642 | 1825 |

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Estradiol Calibration Verification Material (CVM) are in 2 parts. Part I consists of the guideline acceptance criteria which require dose value of stability CVM to fall between ±14% of assigned dose for CVM level 2, ±10% of assigned dose for CVM levels 3 and ±8% 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 ±14% for level 2 and ±10% for levels 3 and ±8% for Cr VM level 4 then additional data review is conducted using part 2 criteria. The acceptance criteria is summarized in Table 3.

| CVM level | Assigned
Dose
(pg/mL) | Guideline Criteria
% difference to assigned
dose | Acceptable Dose
range (pg/mL) | Review Limits |
|-----------|-----------------------------|--------------------------------------------------------|----------------------------------|----------------|
| LE2CVM1 | 0.00 | not applicable | ≤20.00 | Controls are |
| LE2CVM2 | 52 | ±14% | 44.72 - 59.28 | within 2SD of |
| LE2CVM3 | 502 | ±10% | 451.80 - 552.20 | target on each |
| LE2CVM4 | 2323 | ±8% | 2137.16 - 2508.84 | curve |

Table 3 Acceptance criteria for stability of IMMULITE 2000 Estradiol CVM

Traceability:

The IMMULITE Estradiol CVMs are traceable to internal assigned reference calibrators prepared using an Estradiol antigen stock solution and are traceable to internal material which is gravimetrically prepared.

Value Assignment:

The IMMULITE Estradiol CVMs are 4 level materials which are a subset of 7 level Estradiol calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Estradiol reagents and two point adjustors. 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. Four levels of commercially available controls, and 30 patient samples (5 normal patients samples and 25 spiked samples) are 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 FSH CVMs were tested on 15 replicates in total comprised of 5 runs and 3 replicates per run, 5 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 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 -2000 pg/mL. The target values in Table 4 can be considered as guidelines.

| Analyte
target
levels | CVM Level | Target Mean
(pg/mL) | SD | Guideline ±2SD Range
(pg/mL) |
|-----------------------------|-----------------|------------------------|-------|---------------------------------|
| | LE2CVM1 | 0.00 | - | ≤20.00 |
| | LE2CVM2 | 61.5 | 9.85 | 81.20 |
| | LE2CVM3 | 478 | 33.5 | 545 |
| | LE2CVM4 | 2034 | 142.5 | 2319 |
| Assay
Range | 20 - 2000 pg/mL | | | |

Table 4: Analyte Target Range Levels

Each laboratory should establish their limits for acceptability based on methodology, clinical significance and medical decision levels of the test analyte. The representative, total recision 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

9. Conclusion:

The Estradiol Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent the currently marketed The ADVIA Centaur® Enhanced Estradiol (eE2) MCM. 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 Estradiol Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/25/Picture/1 description: The image shows a circular logo with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized symbol that resembles three overlapping waves or curves. The logo is black and white and appears to be a scanned image.

Public Health Service

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

October 25, 2013

SIEMENS HEALTHCARE DIAGNOSTICS INC. c/o Garo Mimaryan 511 Benedict Ave. TARRYTOWN NY 10591

Re: K133124

Trade/Device Name: IMMULITE® 2000 Total T3 Calibration Verification Material IMMULITE® 2000 Total T4 Calibration Verification Material IMMULITE® 2000 TBG Calibration Verification Material IMMULITE® 2000 FSH Calibration Verification Material IMMULITE® 2000 Estradiol Calibration Verification Material Regulation Number: 21 CFR 862.1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: I, reserved Product Code: JJX Dated: September 27, 2013 Received: September 30, 2013

Dear 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. Iisting 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

Page 2-Garo Mimaryan

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

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFF) 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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Carol C. Benson -S for

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

Indications for Use

510(k) Number (if known): K133124

Device Name:

IMMULITE® 2000 Total T3 Calibration Verification Material IMMULITE® 2000 Total T4 Calibration Verification Material IMMULITE® 2000 TBG Calibration Verification Material IMMULITE® 2000 FSH Calibration Verification Material IMMULITE® 2000 Estradiol Calibration Verification Material

Indications for Use:

The IMMULITE® Total T3 Calibration Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Total T3 assay on the IMMULITE 2000 systems.

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

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

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

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

Prescription Use X (21 CFR Part 801 Subpart D)

And/Or

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

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

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

YunglRDCban-S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health 510(k) K133124