K Number

Device Name

IMMULITE 2000 AFP, BR-MA, AND OM-MA CALIBRATION VERIFICATION MATERIAL

Manufacturer

SIEMENS HEALTHCARE DIAGNOSTICS, INC.

Date Cleared

2014-01-14

(133 days)

Product Code

JJX

Regulation Number

862.1660

Intended Use

The IMMULITE® 2000 AFP Calibration Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of AFP antigen. The IMMULITE® BR-MA Calibration Verification Material (CVM) is for in the verification of calibration and reportable range of the IMMULITE BR-MA assay on the IMMULITE 2000 systems The IMMULITE® OM-MA Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE OM-MA assay on the IMMULITE 2000 systems

Device Description

The Calibration Verification Material (CVM) contains one set of four vials each 3mL. CVM1 contain bovine serum matrix with preservatives. CVM2, CVM 3 and CVM4 contain low, intermediate and high levels of human source AFP respectively, in a bovine serum matrix with preservatives. CVMs are supplied frozen in a liquid form. The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM 1 contains a bovine serum matrix with preservatives. CVM2. CVM3 and CVM4 contain low, intermediate and high levels of human source CA 15-3 in a bovine serum matrix with preservatives. CVMs are supplied frozen in liquid form. In addition to using the CVM at their manufactured concentrations, alternate concentrations may be obtained by accurately diluting the assay-specific calibrator levels with each other. The Calibration Verification Material (CVM) contains one set of four vials. 2 mL each. CVM 1 contains a bovine protein/buffer matrix with preservatives. CVM2. CVM3 and CVM4, contain low, intermediate and high levels of CA 125 in a bovine protein/buffer matrix with preservatives. CVMs are supplied in Iyophilized 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

K102086, K122242, K122534

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. The performance studies focus on stability, traceability, and value assignment of the calibration materials.

Therapeutic

No
The device is described as a "Calibration Verification Material" intended for monitoring system performance and verification of calibration and reportable range for an immunoassay system. It does not provide any diagnostic, therapeutic, or preventive function for a patient.

Diagnostic

This device is described as "Calibration Verification Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system". It is used for verifying calibration and reportable range, not for directly diagnosing medical conditions.

SaMD (Software as a Medical Device)

The device description explicitly states that the device is a "Calibration Verification Material (CVM)" which contains physical vials of liquid or lyophilized material. This is a physical reagent, not software.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use/Indications for Use: The intended use explicitly states "for in vitro diagnostic use" for the IMMULITE® OM-MA Calibration Material (CVM). While the other two descriptions don't explicitly use the phrase "in vitro diagnostic," their intended use is for "monitoring system performance" and "verification of calibration and reportable range" of assays that measure specific antigens (AFP, BR-MA, OM-MA) on an immunoassay system. These are all activities performed in vitro (outside the body) to assess the performance of diagnostic tests.
Device Description: The device is a "Calibration Verification Material (CVM)" containing biological components (bovine serum matrix, human source antigens) used to verify the calibration of an immunoassay system. This is a typical characteristic of an IVD accessory or control material.
Intended User/Care Setting: The device is for "prescription use only," which is common for IVDs used in a clinical laboratory setting.
Predicate Device(s): The listed predicate devices are also IVD calibration verification materials (CalCheck). This further supports the classification of this device as an IVD.

Therefore, based on the provided information, this device clearly falls 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® OM-MA Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE OM-MA assay on the IMMULITE 2000 systems.
The IMMULITE® BR-MA Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE BR-MA assay on the IMMULITE 2000 systems.
The IMMULITE® 2000 AFP Calibration Verification Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of AFP antigen.

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

JJX

Device Description

The Calibration Verification Material (CVM) contains one set of four vials. 2 mL each. CVM 1 contains a bovine protein/buffer matrix with preservatives. CVM2. CVM3 and CVM4, contain low, intermediate and high levels of CA 125 in a bovine protein/buffer matrix with preservatives. CVMs are supplied in Iyophilized form.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM 1 contains a bovine serum matrix with preservatives. CVM2. CVM3 and CVM4 contain low, intermediate and high levels of human source CA 15-3 in a bovine serum matrix with preservatives. CVMs are supplied frozen in liquid form. In addition to using the CVM at their manufactured concentrations, alternate concentrations may be obtained by accurately diluting the assay-specific calibrator levels with each other.
The Calibration Verification Material (CVM) contains One set of four vials each 3mL. CVM1 contain bovine serum matrix with preservatives. CVM2, CVM 3 and CVM4 contain low, intermediate and high levels of human source AFP respectively, in a bovine serum matrix with preservatives. CVMs are supplied frozen in a liquid 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)

Stability Study:
IMMULITE® 2000 OM-MA Calibration Verification Materials (CVMs) are stable up to 9 years when stored refrigerated at 2-8°C prior to opening.
Acceptance criteria: dose value of stability CVM to fall between ±10% of assigned dose for CVM levels 2 to 3 and ±11% of assigned dose for CVM level 4. Second part required dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve.
IMMULITE® 2000 BR-MA Calibration Verification Materials (CVMs) are stable up to 4.5 years when stored refrigerated at -20°C prior to opening.
Acceptance criteria: dose value of stability CVM to fall between ±15% of assigned dose for CVM level 2 and ±10% of assigned dose for CVM levels 3 and 4. Second part required dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve.
IMMULITE® 2000 AFP Calibration Verification Materials (CVMs) are stable up to 3.5 years when stored refrigerated at -20°C prior to opening.
Acceptance criteria: dose value of stability CVM to fall between ±15% of assigned dose for CVM levels 2 and ±10% of assigned dose for CVM levels 3 and 4. Second part required dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve.

Value Assignment Testing:
OM-MA CVMs were tested on 27 replicates (9 runs, 3 replicates per run) on 9 systems using 3 different reagent kit lots.
BR-MA CVMs were tested on 27 replicates (9 runs, 3 replicates per run) on 6 systems using 3 different reagent kit lots.
AFP CVMs were tested on 27 replicates (9 runs, 3 replicates per run) on 5 different instruments using 3 different reagent kit lots.

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.

K102086, K122242, K122534

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: K132739

1. Submitter Mailing Address:
  8

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. 511 Benedict Avenue Tarrytown, NY 10591

Garo Mimaryan, MS, RAC Senior Regulatory Affairs Specialist (914)-524-3270 (914)-524-2101 garo.mimarvan@siemens.com January 8, 2014

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

Elecsys CA 125 II CalCheck 5 K102086

See Indications for Use Statement below

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

Table 1: Substantial Equivalence Comparison

SIMILARITIES
	Candidate Device
IMMULITE 2000 OM-MA CVM	Predicate Device
Elecsys CA 125 II CalCheck 5
Intended
Use	The IMMULITE® OM-MA Calibration
Verification Material (CVM) is for in
vitro diagnostic use in the verification of
calibration and reportable range of the
IMMULITE OM-MA assay on the
IMMULITE 2000 systems.	The Elecsys CA 125 II 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 CA 125 11
reagent on the indicated Elecsys and
cobas e immunoassay analyzers, for
in vitro diagnostic use only
Analyte	CA 125	Same
Form	Lyophilized	Same
Stability	Stable until the expiration date when
stored refrigerated.	Same
Storage	2-8°C	Same
	DIFFERENCES
	Candidate Device
IMMULITE 2000 OM-MA CVM	Predicate Device
Elecsys CA 125 II CalCheck 5
Matrix	Bovine serum	Level 1: Equine serum
Levels 2-5 : Human serum
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 OM-MA 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 IMMULITE® 2000 OM-MA Calibration Verification Materials (CVMs) are stable up to 9 years when stored refrigerated at 2-8°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.

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|------|------|------|
| LOPCVM1 | 1 | 1825 | 2555 | 3285 |
| LOPCVM2 | 1 | 1825 | 2555 | 3285 |
| LOPCVM3 | 1 | 1825 | 2555 | 3285 |
| LOPCVM4 | 1 | 1825 | 2555 | 3285 |

Table 2: Stability Protocol Summary

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE OM-MA 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 ±10% of assigned dose for CVM levels 2 to 3 and ±11% 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% of assigned dose for CVM levels 2 to 3 and ±11% of assigned dose for CVM level 4, then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE OM-MA CVMs are traceable to internal assigned reference calibrators prepared using OM-MA antigen stock solution and are traceable to internal material which is gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures.

Value Assignment:

OM-MA CVMs are 4 level materials which are a subset of 9 level OM-MA calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of OM-MA reagents and two point adjustors. The CVMs are manufactured using qualified materials and measurement procedures. 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, Three levels of commercially available controls and 30 samples (5 normal patient samples and 25 normal patients spiked with high patient sample) were used to validate CVM value assignments

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of nine runs and three replicates per run on nine systems and three different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges

Expected 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 9 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 2-500 U/mL. The target values in Table 3 can be considered as guidelines.

| Analyte target
levels | CVM Levels | Target Mean
(U/mL) | SD | Guideline ±2SD Range
(U/mL) | |
|--------------------------|---------------------------------|-----------------------|-------|--------------------------------|-------|
| | CVM1 | 0.00 | - | 0.00 | ≤2.00 |
| | CVM2 | 7.70 | 0.845 | 6.01 | 9.39 |
| | CVM3 | 57.0 | 2.85 | 51.3 | 62.7 |
| | CVM4 | 609 | - | - | - |
| | (85% of CVM4 +
15% of CVM1)* | 518 | 28.5 | 461 | 575 |
| Assay Range | 2 -500 U/mL | | | | |

Table 3: Target Values

*Note: CVM4 requires dilution to ensure the target value is within +10% of the reportable range of the assay.

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

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents .
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic . Calibrators
Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control Material .

Proposed Labeling:

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

ರಿ. Conclusion:

OM-MA 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 CA 125 II 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 OM-MA 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: K132739

1. Submitter Mailing Address:

Contact Person:

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

1. Device Name Proprietarv 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. 511 Benedict Avenue Tarrytown, NY 10591

Garo Mimaryan, MS, RAC . Senior Regulatory Affairs Specialist (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com January 8, 2014

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

Elecsys CA 15-3 II CalCheck 5 K122242

The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM 1 contains a bovine serum matrix with preservatives. CVM2. CVM3 and CVM4 contain low, intermediate and high levels of human source CA 15-3 in a bovine serum matrix with preservatives. CVMs are supplied frozen in liquid form. In addition to using the CVM at their manufactured concentrations, alternate concentrations may be obtained by accurately diluting the assay-specific calibrator levels with each other.

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

For prescription use only

6. Technological Characteristics and Substantial Equivalence Comparison with Predicate:

IMMULITE® 2000 Systems

A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 BR-MA Calibration Verification Material (CVM) is substantially equivalent to the predicate device as summarized in Table 1.

SIMILARITIES
	Candidate Device
IMMULITE 2000 BR-MA CVM	Predicate Device :
Elecsys CA 15-3 II CalCheck 5
Intended
Use	The IMMULITE® BR-MA Calibration
Verification Material (CVM) is for in
vitro diagnostic use in the verification of
calibration and reportable range of the
IMMULITE BR-MA assay on the
IMMULITE 2000 systems	The Elecsys CA 15-3 II 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 CA 15-3 II
reagent on the indicated Elecsys and
cobas e immunoassay analyzers. For
in vitro diagnostic use only.
Analyte	CA 15-3	Same
	DIFFERENCES
	Candidate Device
IMMULITE 2000 BR-MA CVM	Predicate Device :
Elecsys CA 15-3 II CalCheck 5
Form	Liquid	Lyophilized
Matrix	Bovine serum	Level 1: Equine serum matrix
Levels 2-5 : Human serum matrix
Stability	Stable until the expiration date when
stored frozen	Stable until the expiration date when
stored refrigerated.
Storage	-20°C	2-8°C
Use	Single Use Only	Not For Single Use

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 shelf life claim for the IMMULITE 2000 BR-MA 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 IMMULITE® 2000 BR-MA Calibration Verification Materials (CVMs) are stable up to 4.5 years when stored refrigerated at -20°C prior to opening.

Stability Protocol Summary:

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|-----|-----|------|
| LBRCVM1 | 1 | 730 | 912 | 1095 |
| LBRCVM2 | 1 | 730 | 912 | 1095 |
| LBRCVM3 | 1 | 730 | 912 | 1095 |
| LBRCVM4 | 1 | 730 | 912 | 1095 |

Table 2: Stability Protocol Summary

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE BR-MA 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 ±15% of assigned dose for CVM level 2 and ±10% of assigned dose for CVM levels 3 and 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±15% of assigned dose for CVM level 2 and ±10% of assigned dose for CVM levels 3 and 4, then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE BR-MA CVMs are traceable to internal assigned reference calibrators prepared using BR-MA antigen stock solution and are traceable to internal material which is gravimetrically prepared. The CVMs are manufactured using qualified materials and measurement procedures

Value Assignment:

BR-MA CVMs are 4 level materials which are a subset of 7 level BR-MA calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of BR-MA reagents and two point adjustors. 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, Six levels of commercially available controls and 30 samples (5 normal patient samples and 25 spiked patient samples) were used to validate CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs were tested on 27 replicates in total comprised of 9 runs and three replicates per run on 6 systems and 3 different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges.

Expected 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 6 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 1-300 IU/mL. The target values in Table 3 can be considered as guidelines.

| Analyte
target levels | Level | Target Mean
(U/mL) | SD | Guideline ±2SD Range
(U/mL) | |
|--------------------------|------------|-----------------------|------|--------------------------------|-------|
| | 1 | 0.00 | - | 0.00 | ≤1.00 |
| | 2 | 18.8 | 1.4 | 16.0 | 21.6 |
| | 3 | 165 | 8.25 | 149 | 182 |
| | 4 | 291 | 14.5 | 262 | 320 |
| Assay Range | 1-300 U/mL | | | | |

Table 3: Target Values

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:

BR-MA 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 Elecsvs CA 15-3 II 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 BR-MA 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.

K132739 The assigned 510(k) Number:

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 Senior Regulatory Affairs Specialist (914)-524-3270 (914)-524-2101 garo.mimaryan@siemens.com January 8, 2014

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

IMMULITE/IMMULITE 1000 Third Generation PSA CVM K122534

The Calibration Verification Material (CVM) contains One set of four vials each 3mL. CVM1 contain bovine serum matrix with preservatives. CVM2, CVM 3 and CVM4 contain low, intermediate and high levels of human source AFP respectively, in a bovine serum matrix with preservatives. CVMs are supplied frozen in a liquid form.

See Indications for Use Statement below The IMMULITE® 2000 AFP Calibration Verification Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of AFP antigen.

For prescription use only

IMMULITE® 2000 Systems

For prescription use only

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

SIMILARITIES
	Candidate Device
IMMULITE 2000 AFP CVM	Predicate Device
IMMULITE/IMMULITE 1000
Third Generation PSA CVM
Intended
Use	The IMMULITE® 2000 AFP
Calibration Verification Material
(CVM) is intended for monitoring
system performance of the IMMULITE
Immunoassay system for the
quantitative measurement of AFP
antigen.	The IMMULITE®/IMMULITE 1000
Third Generation PSA Calibration
Verification Material (CVM) is
intended for monitoring system
performance of the IMMULITE
Immunoassay system for the
quantitative measurement of PSA
antigen.
Form	Liquid	Same
stability	Stable until the expiration date when
stored frozen	Same
Storage	-20°C	Same
Use	Single Use Only	Same

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

	DIFFERENCES
	Candidate Device
IMMULITE 2000 AFP CVM	Predicate Device
IMMULITE/IMMULITE 1000
Third Generation PSA CVM
Analyte	AFP	PSA
Matrix	Bovine serum	Chicken serum
Assay
Range	0.2–300 IU/mL	0.015 — 20 ng/mL

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 AFP 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 IMMULITE® 2000 AFP Calibration Verification Materials (CVMs) are stable up to 3.5 years when stored refrigerated at -20°C prior to opening.

Stability Protocol Summary:

| CVM Level | Time-Points
(Days) | | | |
|-----------|-----------------------|-----|------|------|
| LAPCVM1 | 1 | 912 | 1095 | 1460 |
| LAPCVM2 | 1 | 912 | 1095 | 1460 |
| LAPCVM3 | 1 | 912 | 1095 | 1460 |
| LAPCVM4 | 1 | 912 | 195 | 1460 |

Table 2: Stability Protocol Summary

Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE AFP 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 ±15% of assigned dose for CVM levels 2 and ±10% of assigned dose for CVM levels 3 and 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±15% of assigned dose for CVM levels 2 and ±10% of assigned dose for CVMs 3 and 4, then additional data review is conducted using part 2 criteria.

Traceability:

The IMMULITE AFP CVMs are traceable to WHO 1st IS 72/225 and are manufactured using qualified materials and measurement procedures.

Value Assignment:

IMMULITE® 2000 AFP (Alpha-fetoprotein) Calibration Materials are 4 level materials which are a subset of 9 level AFP calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of AFP 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. Nine levels of commercially available controls and 61 samples including amniotic fluid samples, pregnancy trimester samples, normal patient samples and spiked AFP samples were used to validate CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples, spiked patient samples and controls using the assigned CVM values. The controls must fall within their target ranges

Expected 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 5 different instruments were used to gain 27 replicates. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected values are provided in the IMMULITE® 2000 CVM Calibration verification Material lot-specific value card. The expected assay range is 0.2 -300 IU/mL. The target values in Table 3 can be considered as guidelines.

Target Values	Table 3:
---------------	----------	--	--	--	--	--	--

Analyte target levels	CVM Level	Target Mean (IU/mL)	SD	Guideline ±2SD Range (IU/mL)
	CVM1	0.00	-	0.00 $≤$ 0.20
	CVM2	3.03	0.225	2.58 - 3.48
	CVM3	47.9	2.4	43.1 - 52.7
	CVM4	413	-	-
(75% CVM4 + 25% CVM1)		310	15.5	279 - 341

*Note: CVM4 requires dilution to ensure that the target value is within the +10% of the reportable

range of the assay.

Standard/Guidance Documents Referenced:

CEN 13640 Stability Testing of In Vitro Diagnostic Reagents .
Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic . Calibrators
Guidance for Industry and FDA Staff Assayed and Unassayed Quality Control Material .

Proposed Labeling:

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

9. Conclusion:

IMMULITE® 2000 AFP (Alpha-fetoprotein) Calibration Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed IMMULITE 1000 Third Generation PSA CVM. 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 AFP Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

Image /page/12/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion around the symbol. The text is in all caps and appears to be in a sans-serif font. The logo is black and white.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

January 14, 2014

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G60 Silver Spring, MD 20993-0002

Siemens Healthcare Diagnostics Inc. c/o Mr. Garo Mimaryan Technical Regulatory Affairs Specialist III 511 Benedict Avenue Tarrytown, NY 10591

Re: K132739

Trade/Device Name: IMMULITE® 2000 AFP Calibration Verification Material IMMULITE® 2000 BR-MA Calibration Verification Material IMMULITE® 2000 OM-MA Calibration Verification Material Regulation Number: 21 CFR §862.1660 Regulation Name: Quality Control Material (assayed and unassayed) Regulatory Class: I Product Code: JJX Dated: December 13, 2013 Received: December 16, 2013

Dear Mr. Mimaryan:

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

If your device is classified (see above) into 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 - Mr. Garo Mimaryan

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 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 regulation (21 CFR Part 801), please contact the Division of Small Manufacturers. International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/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,

Leonthenal Rivarrington -S

Maria M. Chan, Ph.D. for Director

Division of Immunology and Hematology 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 Date: January 31, 2017 See PRA Statement on last page.

510(k) Number (if known) K132739

Device Name

IMMULITE® 2000 AFP Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® 2000 AFP Calibration Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of AFP antigen.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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

THE THE FORT AND FOR FOR FOR FOR FOR FOR FOR ಿಗೆ ಸೇರಿ

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

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

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

510(k) Number (if known) K132739

Device Name

.. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

IMMULITE® 2000 BR-MA Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® BR-MA Calibration Verification Material (CVM) is for in the verification of calibration and reportable range of the IMMULITE BR-MA assay on the IMMULITE 2000 systems

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

🇿 Prescription Use (Part 21 CFR 801 Subpart D)

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

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

FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR F િયારે કુલ ૧૯ મિત

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

Image /page/15/Picture/14 description: The image shows the name "Elizabeth Stafford -S" in a bold, sans-serif font. The letters "FA" are stylized and placed between "Elizabeth" and "Stafford". The text is black against a white background, creating a high contrast.

FORM FDA 3881 (1/14)

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

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

510(k) Number (if known) K132739

Device Name

IMMULITE® 2000 OM-MA Calibration Verification Material

Indications for Use (Describe)

The IMMULITE® OM-MA Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE OM-MA assay on the IMMULITE 2000 systems

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

[X] Prescription Use (Part 21 CFR 801 Subpart D)

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

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

FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR FOR 11 - 120 - 120 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 - 12 ..

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

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