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

K132739 · Siemens Healthcare Diagnostics, Inc. · JJX · Jan 14, 2014 · Clinical Chemistry

Device Facts

• Record ID: K132739
• Device Name: IMMULITE 2000 AFP, BR-MA, AND OM-MA CALIBRATION VERIFICATION MATERIAL
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: JJX · Clinical Chemistry
• Decision Date: Jan 14, 2014
• Decision: SESE
• Submission Type: Abbreviated
• Regulation: 21 CFR 862.1660
• Device Class: Class 1

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® 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 Story

Calibration verification materials (CVM) for IMMULITE 2000 immunoassay systems; used to monitor system performance and verify reportable ranges for AFP, CA 15-3, and CA 125 assays. CVMs consist of multi-level vials (low, intermediate, high) containing human-source or recombinant antigens in bovine serum or protein/buffer matrices. Operated by laboratory personnel on IMMULITE 2000 platforms; output consists of recovered analyte values compared against target means and guideline ranges. Used to ensure assay accuracy and system calibration integrity; supports clinical decision-making by validating that patient sample results fall within verified analytical ranges.

Clinical Evidence

Bench testing only. Stability validated via multi-point testing over shelf life. Value assignment validated using 27 replicates across multiple systems, reagent lots, and runs. Performance verified against target means and ±2SD ranges. No clinical patient data presented.

Technological Characteristics

Four-level calibration verification materials; bovine serum matrix with preservatives. Supplied as lyophilized (OM-MA) or frozen liquid (BR-MA, AFP). Traceable to internal reference calibrators or WHO 1st IS 72/225 (AFP). Storage at 2-8°C or -20°C. Analyte-specific target values provided for IMMULITE 2000 systems.

Indications for Use

Indicated for monitoring system performance and verifying calibration/reportable range of IMMULITE 2000 immunoassay systems for AFP, BR-MA, and OM-MA assays. For prescription use only.

Regulatory Classification

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.

Predicate Devices

• IMMULITE/IMMULITE 1000 Third Generation PSA CVM (k122534)
• Elecsys CA 15-3 II CalCheck 5 (k122242)
• Elecsys CA 125 II CalCheck 5 (k102086)

Submission Summary (Full Text)

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# 510(k) Summary

Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.

The assigned 510(k) Number: K132739

- 1. Submitter Mailing Address:
8

Contact Person:

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

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

- 3. Predicate Device Name Predicate 510(k) No:
- 4. Device Description:
- 5. 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 [e-mail] 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

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.

### See Indications for Use Statement below

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

For prescription use only

IMMULITE® 2000 Systems

{1}------------------------------------------------

# 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<br>IMMULITE 2000 OM-MA CVM | Predicate Device<br>Elecsys CA 125 II CalCheck 5 | |
| Intended<br>Use | The IMMULITE® OM-MA Calibration<br>Verification Material (CVM) is for in<br>vitro diagnostic use in the verification of<br>calibration and reportable range of the<br>IMMULITE OM-MA assay on the<br>IMMULITE 2000 systems. | The Elecsys CA 125 II CalCheck 5 is<br>an assayed control for use in<br>calibration verification and for use in<br>the verification of the assay range<br>established by the Elecsys CA 125 11<br>reagent on the indicated Elecsys and<br>cobas e immunoassay analyzers, for<br>in vitro diagnostic use only | |
| Analyte | CA 125 | Same | |
| Form | Lyophilized | Same | |
| Stability | Stable until the expiration date when<br>stored refrigerated. | Same | |
| Storage | 2-8°C | Same | |
| | DIFFERENCES | | |
| | Candidate Device<br>IMMULITE 2000 OM-MA CVM | Predicate Device<br>Elecsys CA 125 II CalCheck 5 | |
| Matrix | Bovine serum | Level 1: Equine serum<br>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.

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| CVM Level | Time-Points<br>(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

{3}------------------------------------------------

# 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<br>levels | CVM Levels | Target Mean<br>(U/mL) | SD | Guideline ±2SD Range<br>(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 +<br>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.

{4}------------------------------------------------

# 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:

- 2. Device Name Proprietarv Name: Measurand: Type of Test:
Regulation Section: Classification: Products Code:

Panel:

- 3. Predicate Device Name Predicate 510(k) No:
- 4. Device Description:
- 5. 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 [e-mail] 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

{5}------------------------------------------------

# 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<br>IMMULITE 2000 BR-MA CVM | Predicate Device :<br>Elecsys CA 15-3 II CalCheck 5 |
| Intended<br>Use | The IMMULITE® BR-MA Calibration<br>Verification Material (CVM) is for in<br>vitro diagnostic use in the verification of<br>calibration and reportable range of the<br>IMMULITE BR-MA assay on the<br>IMMULITE 2000 systems | The Elecsys CA 15-3 II CalCheck 5<br>is an assayed control for use in<br>calibration verification and for use in<br>the verification of the assay range<br>established by the Elecsys CA 15-3 II<br>reagent on the indicated Elecsys and<br>cobas e immunoassay analyzers. For<br>in vitro diagnostic use only. |
| Analyte | CA 15-3 | Same |
| | DIFFERENCES | |
| | Candidate Device<br>IMMULITE 2000 BR-MA CVM | Predicate Device :<br>Elecsys CA 15-3 II CalCheck 5 |
| Form | Liquid | Lyophilized |
| Matrix | Bovine serum | Level 1: Equine serum matrix<br>Levels 2-5 : Human serum matrix |
| Stability | Stable until the expiration date when<br>stored frozen | Stable until the expiration date when<br>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.

{6}------------------------------------------------

# 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<br>(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.

{7}------------------------------------------------

# 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<br>target levels | Level | Target Mean<br>(U/mL) | SD | Guideline ±2SD Range<br>(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

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:

/

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.

{8}------------------------------------------------

# 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:

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

Panel:

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

4. Device Description:

- 5. 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 [e-mail] 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

{9}------------------------------------------------

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

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

| | DIFFERENCES | |
|----------------|-------------------------------------------|------------------------------------------------------------------------|
| | Candidate Device<br>IMMULITE 2000 AFP CVM | Predicate Device<br>IMMULITE/IMMULITE 1000<br>Third Generation PSA CVM |
| Analyte | AFP | PSA |
| Matrix | Bovine serum | Chicken serum |
| Assay<br>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.

{10}------------------------------------------------

# 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<br>(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

{11}------------------------------------------------

# 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.

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:

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.

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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

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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 [phone] or [phone] 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 [phone] or [phone] 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

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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 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)

Image /page/14/Picture/14 description: The image shows the name "Elizabeth ADSstafford -S" in black font. The letters "ADS" are stylized with a pattern of lines. The rest of the name is in a simple, sans-serif font.

{15}------------------------------------------------

#### 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)

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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 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)

Image /page/16/Picture/14 description: The image shows the name "Elizabeth-A-Stafford-S" in a bold, sans-serif font. The letters are black against a white background. The letters "A" is stylized with a circular design around it.

: