K Number

Device Name

IMMULITE 2000; CORTISOL CALIBRATION VERIFICATION MATERIAL, FOLIC ACID CALIBRATION VERIFICATION MATERIAL, VITAMIN B12 CAL

Manufacturer

Siemens Healthcare Diagnostics Inc.

Date Cleared

2014-07-09

(37 days)

Product Code

JJX

Regulation Number

862.1660

Intended Use

The IMMULITE® Cortisol Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Cortisol assay on the IMMULITE 2000 systems. The IMMULITE® Folic Acid Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Folic Acid assay on the IMMULITE 2000 systems. The IMMULITE® Vitanin B12 Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Vitamin B12 assay on the IMMULITE 2000 systems.

Device Description

The IMMULITE® 2000 Cortisol Calibration Verification Material (CVM) contains one set of four vials each 3mL. CVM1 contains human serum with preservatives and CVM2, CVM3, and CVM4 contain various levels of cortisol in human serum with preservatives. The IMMULITE® 2000 Folic Acid Calibration Verification Material (CVM) contains one set of four vials, 3mL (CVM1) each. when reconstituted. CVM1 contains a lyophilized human albumin based matrix with preservatives. CVM2. CVM3. and CVM4 contain various levels of lyophilized folic acid in human albumin based matrix with preservatives. IMMULITE® 2000 Vitamin B12 Calibration Verification Material (CVM) contains one set of four vials, 3 mL each, when reconstituted. CVM1 contains a lyophilized human albumin-based matrix with preservatives. CVM2, CVM3, and CVM4 contain various levels of lyophilized Vitamin B12 in human albumin-based matrix with preservatives.

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

K133124, K140258

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The document describes calibration materials for an immunoassay system and does not mention any AI or ML components in the device description or performance studies.

Therapeutic

No
This device is for in vitro diagnostic use, specifically for the verification of calibration of assays, not for treating or diagnosing patients directly.

Diagnostic

The device is a calibration material used to verify the calibration of diagnostic assays, not a diagnostic device itself. Its purpose is to ensure the accuracy of other diagnostic systems.

SaMD (Software as a Medical Device)

The device description clearly states that the device contains physical vials with human serum and other materials, indicating it is a physical product, not software only.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use/Indications for Use: The very first sentence for each product explicitly states "for in vitro diagnostic use". This is the primary indicator.
Device Description: The description details materials used (human serum, human albumin based matrix) and their purpose in verifying calibration of diagnostic assays.
Intended User/Care Setting: "For prescription use only" suggests use in a clinical or laboratory setting, consistent with IVDs.
Summary of Performance Studies: The performance studies describe testing using patient serum samples and commercially available controls, which are typical for validating IVDs.
Predicate Device(s): The listed predicate devices are also described as "Calibration Verification Material (CVM)", further indicating the device's role in the diagnostic process.

The device is a calibration verification material used to ensure the accuracy of other in vitro diagnostic assays (IMMULITE Cortisol, Folic Acid, and Vitamin B12 assays). This function is integral to the reliable performance of diagnostic testing.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

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

The IMMULITE® Folic Acid Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Folic Acid assay on the IMMULITE 2000 systems.

The IMMULITE® Vitanin B12 Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Vitamin B12 assay on the IMMULITE 2000 systems.

Product codes (comma separated list FDA assigned to the subject device)

JJX

Device Description

The IMMULITE® 2000 Folic Acid Calibration Verification Material (CVM) contains one set of four vials, 3mL (CVM1) each. when reconstituted. CVM1 contains a lyophilized human albumin based matrix with preservatives. CVM2. CVM3. and CVM4 contain various levels of lyophilized folic acid in human albumin based matrix with preservatives.

IMMULITE® 2000 Vitamin B12 Calibration Verification Material (CVM) contains one set of four vials, 3 mL each, when reconstituted. CVM1 contains a lyophilized human albumin-based matrix with preservatives. CVM2, CVM3, and CVM4 contain various levels of lyophilized Vitamin B12 in human albumin-based matrix with preservatives.

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)

Stability Study:
IMMULITE® 2000 Cortisol Calibration Verification Material (CVM):

Real-time shelf life: 14 months when stored at -20°C prior to opening.
Open component (in-use or open vial) claim: 8 hours at ambient or room temperature (15-25°C) after opening.
Protocol: CVM study protocols run as part of calibrator stability testing. Stability calibrators/CVMs run in duplicate at time points: LCOCVM1, LCOCVM2, LCOCVM3, LCOCVM4 tested at 1, 182, 365, 425 days.
Open component testing: Results determined from a 2-point adjustment. IMMULITE 2000 Cortisol (L2KCO) kit lot 362, lot 090 CVMs tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C).
Acceptance Criteria:
- Part 1 (guideline): dose value of stability calibrators/CVM to fall between +/-20% of assigned dose for CVM level 2, +/-15% of assigned dose for level 3, and +/-19% of assigned dose for level 4.
- Part 2 (review limits): dose value of controls to be within 2 Standard Deviations (SD) of control target value when generated from stability calibrator curve. If Part 1 not met, additional data review conducted using Part 2 criteria.

IMMULITE® 2000 Folic Acid Calibration Verification Material (CVM):

Real-time shelf life: 3.5 years when stored at -20°C prior to opening.
Open component (in-use or open vial) claim: 8 hours at ambient or room temperature (15-25°C) after reconstitution.
Protocol: CVM study protocols run as part of calibrator stability testing. Stability CVMs and reference CVMs run in duplicate at time points: LFOCVM1, LFOCVM2, LFOCVM3, LFOCVM4 tested at 1, 912, 1095, 1280 days.
Open component testing: Results determined from a 2-point adjustment. IMMULITE 2000 Folic Acid (L2KFO) kit lot 446, lot 090B Folic Acid CVMs tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C).
Acceptance Criteria:
- Part 1 (guideline): dose value of stability CVMs to fall between +/-15% of assigned dose for CVM level 2, within +/-10% of assigned dose for level 3, and within +/-12% of assigned dose for CVM level 4.
- Part 2 (review limits): dose value of controls to be within 2 Standard Deviations (SD) of control target value when generated from stability calibrator curve. If Part 1 not met, additional data review conducted using Part 2 criteria.

IMMULITE® 2000 Vitamin B12 Calibration Verification Material (CVM):

Real-time shelf life: 69 months when stored at -20°C prior to opening.
Open component (in-use or open vial) claim: 8 hours at room (ambient) temperature (15-25°C) after reconstitution.
Protocol: CVM study protocols run as part of calibrator stability testing. Testing run in duplicate with time points: LVBCVM1, LVBCVM2, LVBCVM3, LVBCVM4 tested at 0, 67, 68, 69 months.
Open component testing: Results determined from a 2-point adjustment. IMMULITE 2000 Vitamin B12 (L2KVB) kit lot 467, lot 108 Vitamin B12 CVMs tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C).
Acceptance Criteria:
- Part 1 (guideline): dose value of stability calibrator/CVM to fall between +/-10% of assigned dose for CVM level 2 and level 3, and within +/-21% of assigned dose for CVM level 4.
- Part 2 (review limits): dose value of controls to be within 2SD of control target value when generated from stability calibrator curve. If Part 1 not met, additional data review conducted using Part 2 criteria.

Value Assignment Test:
IMMULITE® 2000 Cortisol Calibration Verification Material:

Sample size/Data source: IMMULITE Cortisol CVMs are 4 level materials subset of 8 level Cortisol calibrators. Quality control performed by calculating recovery of patient samples, spiked patient samples, and controls. Six levels of commercially available controls and 25 patient serum samples, 3 spiked normal serum samples, and 5 normal serum samples used.
Key Results: Value assigned using assigned reference calibrators. CVM dose values generated using curve generated by assigned reference calibrators. CVM values calculated based on recovered values for each run on each instrument independently and averaged across all systems. Expected assay range 1 to 50 g/dL. Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and +/- 2 Standard Deviation (SD).

IMMULITE® 2000 Folic Acid Calibration Verification Material:

Sample size/Data source: IMMULITE Folic Acid CVMs are 4 level materials subset of 8 level Folic Acid calibrators. Quality control performed by calculating recovery of patient samples and controls, controls must fall within their target ranges. Six levels of commercially available controls and 14 patient serum samples used.
Key Results: Value assigned using assigned reference calibrators. CVM dose values generated using curve generated by assigned reference calibrators. CVM values calculated based on recovered values for each run on each instrument independently and averaged across all systems. Expected assay range 1 to 24 ng/mL. Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and +/- 2 Standard Deviation (SD).

IMMULITE® 2000 Vitamin B12 Calibration Verification Material:

Sample size/Data source: IMMULITE® 2000 Vitamin B12 CVMs are 4 level materials subset of 8 level Vitamin B12 calibrators. Quality control performed by calculating recovery of patient samples and controls. Eight levels of commercially available controls and 21 patient serum samples used.
Key Results: Value assigned using internal standard and assigned reference calibrators. CVM dose values generated using curve generated by assigned reference calibrators. CVM values calculated based on recovered values for each instrument independently and averaged across all systems. Expected assay range 150 to 1000 pg/mL. Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and +/- 2 Standard Deviation (SD).

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

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K133124, K140258

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

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

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: ______k1414444

| 1. Submitter
Mailing Address: | Siemens Healthcare Diagnostics Inc.
5210 Pacific Concourse Drive
Los Angeles, CA 90045 |
|------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person:
Phone Number:
Fax Number:
E-mail Address:
Date Prepared: | Donna Velasquez
Regulatory Technical Specialist
(310)-645-8200 x7403
(310)-645-9999
donna.velasquez@siemens.com
May 30, 2014 |
| 2. Device Name
Proprietary Name:
Measurand:
Type of Test:
Regulation Section:
Classification:
Products Code:
Panel: | IMMULITE® 2000 Cortisol Calibration Verification Material
Quality Control materials for IMMULITE® 2000 Cortisol assay
Calibration Verification Material (CVM) for IMMULITE® 2000
Cortisol assay
21 CFR 862.1660, Quality Control Material
Class I Reserved
JJX - Single (Specified) Analyte Controls (Assayed and
Unassayed)
Clinical Chemistry (75) |
| 3. Predicate Device Name
Predicate 510(k) No: | IMMULITE® 2000 Total T3 Calibration Verification Material
(CVM)
K133124 |
| 4. Device Description: | The IMMULITE® 2000 Cortisol Calibration Verification Material
(CVM) contains one set of four vials each 3mL. CVM1 contains
human serum with preservatives and CVM2, CVM3, and CVM4
contain various levels of cortisol in human serum
with
preservatives. |
| 5. Intended Use:
Indication for Use: | See Indications for Use Statement below
The IMMULITE® Cortisol Calibration Verification Material
(CVM) is for in vitro diagnostic use in the verification of
calibration of the IMMULITE Cortisol assay on the IMMULITE
2000 systems |
| Special Conditions for
Use Statement(s):
Special Instrument
Requirements: | 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 Cortisol Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.

SIMILARITIES
	Candidate Device
IMMULITE 2000 Cortisol CVM	Predicate Device
IMMULITE 2000 Total T3 CVM
Intended
Use	The IMMULITE® Cortisol Calibration
Verification Material (CVM) is for in
vitro diagnostic use in the verification of
calibration of the IMMULITE Cortisol
assay on the IMMULITE 2000 systems.	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
Storage	-20°C	Same
Form	Liquid	Same
Stability	Stable unopened until the
expiration date	Same
Levels	4	Same
Matrix	Human Serum with preservatives	Same
Use	Single Use Only	Same
	DIFFERENCES
	Candidate Device
IMMULITE 2000 Cortisol CVM	Predicate Device
IMMULITE 2000 Total T4 CVM
Analyte	Cortisol	Total T3

Table 1: Substantial Equivalence Comparison

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 real-time shelf life and open component (in-use or open vial) claim for the IMMULITE 2000 Cortisol Calibration 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 14 months when stored at -20°C prior to opening and stable for 8 hours at ambient or room temperature (15-25°C) after opening.

Stability Protocol Summary:

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

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|-----|-----|-----|
| LCOCVM1 | 1 | 182 | 365 | 425 |
| LCOCVM2 | 1 | 182 | 365 | 425 |
| LCOCVM3 | 1 | 182 | 365 | 425 |
| LCOCVM4 | 1 | 182 | 365 | 425 |

Table 2: Stability Protocol Summary

For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Cortisol (L2KCO) kit lot 362, lot 090 CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the Cortisol Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability

calibrators/CVM to fall between ±20% of assigned dose for CVM level 2, ±15% of assigned dose for level 3 and ±19% of assigned dose for level 4. Part 2 review limits criteria which require dose value of the controls to be within 2 Standard Deviations (SD) 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, ±15% of assigned dose for level 3 and within ±19% of assigned dose for level 4, then additional data review is conducted using part 2 criteria.

Traceability:

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

Value Assignment:

The IMMULITE Cortisol CVMs are 4 level materials which are a subset of 8 level Cortisol calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Cortisol reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The CVMs are manufactured using qualified materials and measurement procedures. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. Six levels of commercially available controls and 25 patient serum samples, 3 spiked normal serum samples and 5 normal serum samples were used to validate calibrator/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, 3 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 Material lotspecific value card. The expected assay range is 1 to 50 g/dL. The target values in Table 3 can be considered as guidelines.

| Analyte target
levels | CVM Level | *Target
Mean
g/dL) | Standard
Deviation
(SD) | Guideline ±2SD
Range | |
|--------------------------|--------------|--------------------------|-------------------------------|-------------------------|------|
| | LCOCVM1 | 0.00 | - | 0. | 1.0 |
| | LCOCVM2 | 4.54 | 0.455 | 3. | 5.45 |
| | LCOCVM3 | 18.7 | 1.4 | 15 | 21.5 |
| | LCOCVM4 | 54.5 | 5.2 | 44 | 64.9 |
| Assay Range | 1 to 50 g/dL | | | | |

Table 3: Analyte Target Range Values

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

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

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents

Guidance for Industry - Abbreviated 510(k) Submissions for In Vitro Diagnostic Calibrators Guidance for Industry and FDA Staff - Assayed and Unassayed Quality Control Material

Proposed Labeling:

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

8. Conclusion:

The IMMULITE® 2000 Cortisol Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Cortisol 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: K141444

1. Submitter Mailing Address:
  Contact Person:

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

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

Panel:

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

Siemens Healthcare Diagnostics Inc. 5210 Pacific Concourse Drive Los Angeles. CA 90045

Donna Velasquez Regulatory Technical Specialist (310) 645-8200 x7403 (310) 645-9999 donna.velasquez@siemens.com May 30, 2014

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

IMMULITE 2000 DHEA-SO4 Calibration Verification Material (CVM) K140258

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

For prescription use only

IMMULITE® 2000 Systems

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

SIMILARITIES
	Candidate Device
IMMULITE 2000 Folic Acid CVM	Predicate Device
IMMULITE 2000 DHEA-SO4
CVM
Intended
Use	The IMMULITE® Folic Acid
Calibration Verification Material (CVM)
is for in vitro diagnostic use in the
verification of calibration of the
IMMULITE Folic Acid assay on the
IMMULITE 2000 systems	The IMMULITE® DHEA-SO4
Calibration Verification Material
(CVM) is for in vitro diagnostic use
in the verification of calibration of
the IMMULITE DHEA-SO4 assay
on the IMMULITE 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

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

	DIFFERENCES
	Candidate Device
IMMULITE 2000 Folic Acid CVM	Predicate Device
IMMULITE 2000 DHEA-SO4
CVM
Analyte	Folic Acid	DHEA-SO4
Matrix	Human Albumin with preservatives	Human Serum with Preservatives

7. Non-Clinical Performance Testing

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

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 Folic Acid 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 at -20°C prior to opening, and for 8 hours at ambient or room temperature (15-25°C) after reconstitution.

Stability Protocol Summary:

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

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|-----|------|------|
| LFOCVM1 | 1 | 912 | 1095 | 1280 |
| LFOCVM2- | 1 | 912 | 1095 | 1280 |
| LFOCVM3 | 1 | 912 | 1095 | 1280 |
| LFOCVM4 | 1 | 912 | 1095 | 1280 |

Table 2: Stability Protocol Summary

For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Folic Acid (L2KFO) kit lot 446, lot 090B Folic Acid CVMs were tested at 2hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Folic Acid Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability CVMs to fall between ±15% of the assigned dose for CVM level 2, within ±10% of the assigned dose for level 3 and within ±12% of assigned dose for CVM level 4. Part 2 review limits criteria which require dose value of the controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±15% of the assigned dose for CVM level 2, within ±10% of the assigned dose for level 3 and within ±12% of assigned dose for CVM level 4 then additional data review is conducted using part 2 criteria.

Traceability:

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

Value Assignment:

The IMMULITE Folic Acid CVMs are 4 level materials which are a subset of 8 level Folic Acid calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Folic Acid reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges. Six levels of commercially available controls and 14 patient serum samples were used to validate calibrator/CVM value assignments.

Expected Values/Target Values/Reference Range:

The CVMs are manufactured using qualified materials and measurement procedures. The Folic Acid CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run on 6 IMMULITE 2000 systems and 3 different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. The CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and 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 to 24 ng/mL. The target values in Table 3 can be considered as guidelines.

Table 3: Analyte Target Range Levels

| Analyte target
levels | CVM Level | *Target
Mean
(ng/mL) | Standard
Deviation
(SD) | Guideline ±2SD Range
(ng/mL) |
|--------------------------|---------------|----------------------------|-------------------------------|---------------------------------|
| | LFOCVM1 | 0.00 | - | 0.00
1.0 |
| | LFOCVM2 | 3.11 | 0.28 | 2.55
3.67 |
| | LFOCVM3 | 12.4 | 0.75 | 10.9
13.9 |
| | LFOCVM4 | 26.3 | 1.6 | 23.1
29.5 |
| Assay Range | 1 to 24 ng/mL | | | |

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 Folic Acid Calibration Verification Material is substantially equivalent to the predicate device intended for similar use. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Folic Acid 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: K141444

the assigned 510(k) Number:	K141444
1. Submitter
Mailing Address:	Siemens Healthcare Diagnostics Inc.
5210 Pacific Concourse Drive
Los Angeles, CA 90045
Contact Person:
Phone Number:
Fax Number:
E-mail Address:
Date Prepared:	Donna Velasquez
Regulatory Technical Specialist
(310)-645-8200 x7403
(310)-645-9999
donna.velasquez@siemens.com
May 30, 2014
2. Device Name
Proprietary Name:
Measurand:
Type of Test:
Regulation Section:
Classification:
Products Code:
Panel:	IMMULITE® 2000 Vitamin B12 Calibration Verification Material
Quality Control materials for IMMULITE 2000 Vitamin B12
Calibration Verification Material (CVM) for IMMULITE® 2000
Vitamin B12 assay
21 CFR 862.1660, Quality Control Material
Class I Reserved
JJX - Single (Specified) Analyte Controls (Assayed and Unassayed)
Clinical Chemistry (75)
3. Predicate Device Name
Predicate 510(k) No:	IMMULITE® 2000 DHEA-SO4 Calibration Verification Material
K140258
4. Device Description:	IMMULITE® 2000 Vitamin B12 Calibration Verification Material
(CVM) contains one set of four vials, 3 mL each, when reconstituted.
CVM1 contains a lyophilized human albumin-based matrix with
preservatives. CVM2, CVM3, and CVM4 contain various levels of
lyophilized Vitamin B12 in human albumin-based matrix with
preservatives.
5. Intended Use:
Indication for Use:	See Indications for Use Statement below
The IMMULITE® Vitamin B12 Calibration Verification Material
(CVM) is for in vitro diagnostic use in the verification of the
IMMULITE Vitamin B12 assay on the IMMULITE 2000 systems
Special Conditions for
Use Statement(s):
Special Instrument
Requirements:	For prescription use only
IMMULITE® 2000 Systems

1. Technological Characteristics A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 Vitamin B12 and Substantial Equivalence Calibration Verification Material (CVM) is substantially equivalent Comparison with Predicate: to the predicate device, as summarized in Table 1.

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate Device
IMMULITE 2000 Vitamin B12 CVM	Predicate Device
IMMULITE 2000 DHEA-SO4 CVM
Intended
Use	The IMMULITE® Vitamin B12
Calibration Verification Material
(CVM) is for in vitro diagnostic use in
the verification of calibration of the
IMMULITE Vitamin B12 assay on the
IMMULITE 2000 systems.	The IMMULITE® DHEA-SO4
Calibration Verification Material
(CVM) is for in vitro diagnostic use in
the verification of calibration of the
IMMULITE DHEA-SO4 assay on the
IMMULITE 2000 systems
Form	Lyophilized	Same
Stability	Stable unopened until the
expiration date	Same
Storage	-20°C	Same
Levels	4	Same
Use	Single Use Only	Same

	DIFFERENCES
	Candidate Device
IMMULITE 2000 Vitamin B12 CVM	Predicate Device
IMMULITE 2000 DHEA-SO4 CVM
Analyte	Vitamin B12	DHEA-SO4
Matrix	Human Albumin with preservatives	Human Serum with preservatives

7. Non-Clinical Performance Testing

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

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 Vitamin B12 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 69 months when stored at -20°C prior to opening and stable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution.

Stability Protocol Summary:

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

| CVM Level | Time-Points
(Months) | | | |
|-----------|-------------------------|----|----|----|
| LVBCVM1 | 0 | 67 | 68 | 69 |
| LVBCVM2 | 0 | 67 | 68 | 69 |
| LVBCVM3 | 0 | 67 | 68 | 69 |
| LVBCVM4 | 0 | 67 | 68 | 69 |

For Open Component testing, the results were determined from a 2-point adjustment. Using IMMULITE 2000 Vitamin B12 (L2KVB) kit lot 467, lot 108 Vitamin B12 CVMs were tested at 2hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Vitamin B12 Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±10% of assigned dose for CVM level 2 and level 3 and within ±21% of assigned dose for CVM level 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±10% for level 3 and ±21% for level 4, then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE Vitamin B12 CVMs are traceable to an internal standard. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

The IMMULITE® 2000 Vitamin B12 CVMs are 4 level materials which are a subset of 8 level Vitamin B12 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Vitamin B12 reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value 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 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. Eight levels of commercially available controls and 21 patient serum samples were used to validate CVM value assignments.

Expected Values/Target Values/Reference Range:

The Vitamin B12 CVMs were tested on 24 replicates in total comprised of 12 runs and 2 replicates per run, 3 IMMULITE 2000 and 5 IMMULITE/IMMULITE 1000 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 150 to 1000 pg/mL. The target values in Table 3 can be considered as guidelines.

| Analyte target
levels | Level | *Target Mean
(ng/mL) | Standard
Deviation
(SD) | Guideline ±2SD Range
(ng/mL) |
|--------------------------|-------------------|-------------------------|-------------------------------|---------------------------------|
| | LVBCVM1 | 0.00 | - | 0.00 - 150 |
| | LVBCVM2 | 234 | 23.5 | 187 - 281 |
| | LVBCVM3 | 579 | 34.5 | 510 - 648 |
| | LVBCVM4 | 1144 | 194.5 | 755 - 1533 |
| Assay Range | 150 to 1000 pg/mL | | | |

Table 3: Analyte Target Range Levels

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents

Guidance for Industry - Abbreviated 510(k) Submissions for In Vitro Diagnostic Calibrators Guidance for Industry and FDA Staff - Assayed and Unassayed Quality Control Material

Proposed Labeling:

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

Conclusion: 9.

The IMMULITE® 2000 Vitamin B12 Calibration Material is substantially equivalent to the predicate device intended for similar use. The substantial equivalence of the device is supported by the non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 Vitamin B12 Calibration Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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Public Health Service

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

July 9, 2014

SIEMENS HEALTHCARE DIAGNOSTICS, INC. C/O DONNA VELASQUEZ REGULATORY TECHNICAL SPECIALIST 5210 PACIFIC CONCURSE DRIVE LOS ANGELES CA 90045

Re: K141444

Trade/Device Name: IMMULITE® 2000 Cortisol Calibration Verification Material IMMULITE® 2000 Folic Acid Calibration Verification Material IMMULITE® 2000 Vitamin B12 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: June 3, 2014 Received: June 5, 2014

Dear Donna Velasquez:

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 Part 801); medical device reporting (reporting of medical

Page 2 - Ms. Donna Velasquez

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

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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/Resources/orYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/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 H. Lias -S

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

Enclosure

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

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

510(k) Number (if known) K141444

Device Name

IMMULITE® 2000 Cortiso! Calibration Verification Material IMMULITE® 2000 Folic Acid Calibration Verification Material IMMULITE® 2000 Vitamin B12 Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® Corlisol Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Cortisol assay on the IMMULITE 2000 systems.

The IMMULITE® Folic Acid Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Folic Acid assay on the IMMULITE 2000 systems.

The IMMULITE® Vitanin B12 Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Vitamin B12 assay on the IMMULITE 2000 systems.

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

2 Prescription Use (Part 21 CFR 801 Subpart D)

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

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

。

Concurrence of Center for Devices and Radiological Health (CDRH) (Signalure)

Yung W. Chan -S

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