IMMULITE: 2000 FREE T4 CALIBRATION VERIFICATION MATERIAL, 2000 IGF-I CALIBRATION VERIFICATION MATERIAL, 2000 PROLACTIN C

K140818 · Siemens Healthcare Diagnostics, Inc. · JJX · May 1, 2014 · Clinical Chemistry

Device Facts

• Record ID: K140818
• Device Name: IMMULITE: 2000 FREE T4 CALIBRATION VERIFICATION MATERIAL, 2000 IGF-I CALIBRATION VERIFICATION MATERIAL, 2000 PROLACTIN C
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: JJX · Clinical Chemistry
• Decision Date: May 1, 2014
• Decision: SESE
• Submission Type: Abbreviated
• Regulation: 21 CFR 862.1660
• Device Class: Class 1

Intended Use

The IMMULITE® Free T4 Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Free T4 assay on the IMMULITE 2000 systems. The IMMULITE® IGF-1 Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE IGF-1 assay on the IMMULITE 2000 systems. The IMMULITE® Prolactin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Prolactin assay on the IMMULITE 2000 systems.

Device Story

The IMMULITE 2000 Calibration Verification Materials (CVM) are multi-level, processed serum/buffer-based materials used to verify the calibration of specific assays (Free T4, IGF-1, Prolactin) on the IMMULITE 2000 system. The device consists of four vials at varying analyte concentrations. The CVMs are processed by the IMMULITE 2000 instrument; the system compares recovered values against assigned target ranges to confirm assay calibration accuracy. Used in clinical laboratories by trained technicians. The output provides a verification of the instrument's calibration curve, ensuring the accuracy of patient sample testing. This allows healthcare providers to rely on assay results for clinical decision-making, benefiting patients by ensuring diagnostic test reliability.

Clinical Evidence

No clinical data. Bench testing only. Stability validated via shelf-life studies at -20°C or 2-8°C. Value assignment validated using 27 replicates across multiple runs, reagent lots, and IMMULITE 2000 systems. Acceptance criteria require recovery within ±10% (or ±15% for specific levels) of assigned dose.

Technological Characteristics

Multi-level (4) lyophilized or liquid materials. Matrices: processed human serum, bovine protein/buffer, or equine serum with sodium azide/preservatives. Sensing principle: immunoassay-based calibration verification on IMMULITE 2000 platform. Storage: -20°C or 2-8°C. Traceability: internal gravimetric standards or 3rd IS 84/500.

Indications for Use

Indicated for in vitro diagnostic use to verify calibration of IMMULITE 2000 Free T4, IGF-1, and Prolactin assays on IMMULITE 2000 systems. 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.

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: __k140818_________________________________________________________________________________________________________________________________________

| 1. | Submitter<br>Mailing Address: | Siemens Healthcare Diagnostics Inc.<br>511 Benedict Avenue<br>Tarrytown, NY 10591 |
|----|------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Contact Person:<br>Phone Number:<br>Fax Number:<br>E-mail Address:<br>Date Prepared: | Ernest Joseph<br>Senior Manager, Regulatory Affairs<br>(914)-524-2431<br>(914)-524-2101<br>[e-mail]<br>March 31, 2014 |
| | 2. Device Name<br>Proprietary Name:<br>Measurand:<br>Type of Test:<br>Regulation Section:<br>Classification:<br>Products Code:<br>Panel: | IMMULITE® 2000 Free T4 Calibration Verification Material<br>Quality Control materials for IMMULITE® 2000 Free T4 assay<br>Calibration Verification Material (CVM) for IMMULITE® 2000<br>Free T4 assay<br>21 CFR 862.1660, Quality Control Material<br>Class I Reserved<br>JJX - Single (Specified) Analyte Controls (Assayed and<br>Unassayed)<br>Clinical Chemistry (75) |
| | 3. Predicate Device Name<br>Predicate 510(k) No: | IMMULITE® 2000 Total T4 Calibration Verification Material<br>(CVM)<br>K133124 |
| | 4. Device Description: | The IMMULITE® 2000 Free T4 Calibration Verification Material<br>(CVM) contains one set of four vials each ImL. CVMIcontains a<br>lyophilized processed human serum matrix with 1.58% sodium<br>azide and preservative and CVM2, CVM3, and CVM4 contain<br>various levels of lyophilized Free T4 in a processed human serum<br>matrix with 1.58% sodium azide and preservative. CVMs are<br>supplied frozen in a lyophilized form. |
| | 5. Intended Use:<br>Indication for Use: | See Indications for Use Statement below<br>The IMMULITE® Free T4 Calibration Verification Material<br>(CVM) for in vitro diagnostic use in the verification of calibration<br>of the IMMULITE Free T4 assay on the IMMULITE 2000 systems |
| | Special Conditions for<br>Use Statement(s):<br>Special Instrument<br>Requirements: | For prescription use only<br>IMMULITE® 2000 Systems |

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

### 7. Non-Clinical Performance Testing

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

### Stability Summary:

The stability study was conducted to validate shelf life claim for the IMMULITE 2000 Free T4 Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM. The Calibration Verification Materials are stable up to 4 years when stored at -20°C prior to opening and stable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution.

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### 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<br>(Days) | | | |
|-----------|-----------------------|------|------|------|
| LFT4CVM1 | 1 | 1095 | 1280 | 1460 |
| LFT4CVM2 | 1 | 1095 | 1280 | 1460 |
| LFT4CVM3 | 1 | 1095 | 1280 | 1460 |
| LFT4CVM4 | 1 | 1095 | 1280 | 1460 |

### Table 2: Stability Protocol Summary

### Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Free T4 requires dose value of stability CVMs to fall between ±10% of assigned dose for CVM level 2 and 3 and within ±15% of assigned dose for level 4. Part 2 review limits criteria requires 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 levels 2 and 3 and 15% for level 4 then additional data review is conducted using part 2 criteria.

### Traceability:

The IMMULITE Free T4 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 Free T4 CVMs are 4 level materials which are a subset of 6 level Total Free T4 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Free T4 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 30 normal samples were used to validate CVM value assignments.

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### Expected Values/Target Values/Reference Range:

Each CVM level was tested for a total of 27 replicates; 9 runs and 3 replicates per run, 5 different reagent kit lots and 9 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 0.3 - 6 ng/dL. The target values in Table 3 can be considered as guidelines.

| Analyte target<br>levels | CVM Level | Target<br>Mean<br>(ng/dL) | Standard<br>Deviation<br>(SD) | Guideline ±2SD Range<br>(ng/dL) |
|--------------------------|---------------|---------------------------|-------------------------------|---------------------------------|
| | LFT4CVM1 | 0.00* | - | ≤0.3 |
| | LFT4CVM2 | 1.51 | 0.09 | 1.69 |
| | LFT4CVM3 | 2.90 | 0.145 | 3.19 |
| | LFT4CVM4 | 6.85* | 0.515 | 7.88 |
| Assay Range | 0.3 - 6 ng/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 < or > the assay lower and upper range.

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

### Standard/Guidance Documents Referenced:

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

### Proposed Labeling:

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

#### 8. Conclusion:

The IMMULITE® 2000 Free T4 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 Free T4 Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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### 510(k) Summary

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

The assigned 510(k) Number:

| <b>1. Submitter</b> | Siemens Healthcare Diagnostics Inc. |
|---------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Mailing Address: | 511 Benedict Avenue<br>Tarrytown, NY 10591 |
| Contact Person: | Ernest Joseph |
| | Senior Manager, Regulatory Affairs |
| Phone Number: | (914)-524-2431 |
| Fax Number: | (914)-524-2101 |
| E-mail Address: | [e-mail] |
| Date Prepared: | March 31, 2014 |
| <b>2. Device Name</b> | |
| Proprietary Name: | IMMULITE® 2000 IGF-I Calibration Verification Material |
| Measurand: | Quality Control materials for IMMULITE® 2000 IGF-I assay |
| Type of Test: | Calibration Verification Material (CVM) for IMMULITE® 2000 IGF-I assay |
| Regulation Section: | 21 CFR 862.1660, Quality Control Material |
| Classification: | Class I Reserved |
| Products Code: | JJX - Single (Specified) Analyte Controls (Assayed and Unassayed) |
| Panel: | Clinical Chemistry (75) |
| <b>3. Predicate Device Name</b> | IMMULITE 2000 HCG CVM |
| Predicate 510(k) No: | K133128 |
| <b>4. Device Description:</b> | The IMMULITE® 2000 IGF-I Calibration Verification Material (CVM) contains one set of four vials, 2mL (CVM1) each. CVM1 contains a processed bovine protein/buffer matrix with preservatives. CVM2, CVM3, and CVM4 contain various levels of IGF-I in a processed bovine protein/buffer matrix with preservatives. The CVMs are supplied frozen in a liquid form. |
| <b>5. Intended Use:</b> | |
| Indication for Use: | See Indications for Use Statement below<br>The IMMULITE® IGF-I Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE IGF-I assay on the IMMULITE 2000 systems |

Special Conditions for

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Image /page/5/Picture/0 description: The image contains the word "SIEMENS" in all capital letters. The text is written in a bold, sans-serif font. The letters are black against a white background.

| Use Statement(s): | For prescription use only |
|-------------------------------------|---------------------------|
| Special Instrument<br>Requirements: | 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 IGF-I 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 IGF-I CVM | Predicate Device<br>IMMULITE 2000 HCG CVM |
| Intended<br>Use | The IMMULITE® IGF-I Calibration<br>Verification Material (CVM) is for in<br>vitro diagnostic use in the verification of<br>calibration of the IMMULITE IGF-I<br>assay on the IMMULITE 2000 systems | The IMMULITE® HCG Calibration<br>Verification Material (CVM) is for in<br>vitro diagnostic use in the verification<br>of calibration of the IMMULITE<br>HCG assay on the IMMULITE 2000<br>systems |
| Form | Liquid | Same |
| Levels | 4 | Same |
| Stability | Stable unopened until the expiration date | Same |
| Storage | ≤-20°C | Same |
| Use | Single Use Only | Same |

| | DIFFERENCES | |
|---------|---------------------------------------------|-------------------------------------------|
| | Candidate Device<br>IMMULITE 2000 IGF-I CVM | Predicate Device<br>IMMULITE 2000 HCG CVM |
| Analyte | IGF-I | HCG |
| Matrix | Bovine protein/buffer 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 intended 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 IGF-I 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 2.5 years when stored at -20°C prior to opening, and for 8 hours at ambient temperature (room temperature) after opening.

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### 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<br>(Days) | | | |
|-----------|-----------------------|-----|-----|-----|
| LGFCVM1 | 1 | 365 | 730 | 912 |
| LGFCVM2 | 1 | 365 | 730 | 912 |
| LGFCVM3 | 1 | 365 | 730 | 912 |
| LGFCVM4 | 1 | 365 | 730 | 912 |

### Table 2: Stability Protocol Summary

### Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE IGF-I requires dose value of stability CVMs to fall between ±10% of the assigned dose. Part 2 review limits criteria 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 each level then additional data review is conducted using part 2 criteria.

### Traceability:

The IMMULITE IGF-I 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 IGF-I CVMs are 4 level materials which are a subset of 6 level IGF-I calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of IGF-I 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. Two levels of commercially available controls and 60 samples (10 spiked samples and 50 normal patient samples) were used to validate CVM value assignments.

### Expected Values/Target Values/Reference Range:

The CVMs are manufactured using qualified materials and measurement procedures. The IGF-I CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run on 7 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

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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 Up to 1600 ng/mL . The target values in Table 3 can be considered as guidelines.

| Analyte target<br>levels | CVM Level | Target<br>Mean<br>(ng/mL) | Standard<br>Deviation<br>(SD) | Guideline ±2SD Range<br>(ng/mL) |
|--------------------------|------------------|---------------------------|-------------------------------|---------------------------------|
| | LGFCVM1 | 0.00 | - | ≤25.00 |
| | LGFCVM2 | 34.7 | 2.8 | 29.1 |
| | LGFCVM3 | 237 | 15.5 | 206 |
| | LGFCVM4 | 1727* | 86.5 | 1554 |
| Assay Range | Up to 1600 ng/mL | | | |

### Table 3: Analyte Target Range Levels

*Note: when CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software.

If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.

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

Standard/Guidance Documents Referenced:

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

### Proposed Labeling:

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

#### 8. Conclusion:

The IMMULITE® 2000 IGF-1 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 IGF-I Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

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### 510(k) Summary

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

The assigned 510(k) Number: k140818

- 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):

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

Ernest Joseph Senior Manager, Regulatory Affairs (914)-524-2431 (914)-524-2101 ernest.joseph(@siemens.com March 31, 2014

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

IMMULITE® 2000 Growth Hormone Calibration Verification Material K133128

IMMULITE® 2000 Prolactin Calibration Verification Material (CVM) contains one set of four vials, 3 mL each. CVM1 contains a lyophilized equine serum/buffer matrix with preservative. CVM2, CVM3, and CVM4 contain various levels of lyophilized prolactin in an equine serum/buffer matrix with preservative CVMs are supplied frozen in a lyophilized form.

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

For prescription use only

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Special Instrument Requirements:

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

| SIMILARITIES | | | |
|-----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| | Candidate Device<br>IMMULITE 2000 Prolactin CVM | Predicate Device<br>IMMULITE 2000 Growth Hormone<br>CVM | |
| Intended<br>Use | The IMMULITE® Prolactin Calibration<br>Verification Material (CVM) is for in<br>vitro diagnostic use in the verification of<br>calibration of the IMMULITE Prolactin<br>assay on the IMMULITE 2000 systems. | The IMMULITE® Growth Hormone<br>Calibration Verification Material<br>(CVM) is for in vitro diagnostic use in<br>the verification of calibration of the<br>IMMULITE Growth Hormone assay<br>on the IMMULITE 2000 systems | |
| Form | Lyophilized | Same | |
| Storage | 2-8°C | Same | |
| Stability | Stable unopened until the<br>expiration date | Same | |
| Levels | 4 | Same | |
| Matrix | Equine Serum with preservatives | Same | |
| Use | Single Use Only | Same | |

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

| | DIFFERENCES | |
|---------|-------------------------------------------------|---------------------------------------------------------|
| | Candidate Device<br>IMMULITE 2000 Prolactin CVM | Predicate Device<br>IMMULITE 2000 Growth Hormone<br>CVM |
| Analyte | Prolactin | Growth Hormone |

### 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 Prolactin 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 years when stored at 2-8°C prior to opening and stable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution.

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### 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.

### Table 2: Stability Protocol Summary

| CVM Level | Time-Points<br>(Days) | | | |
|-----------|-----------------------|-----|-----|------|
| LPRCVM1 | 1 | 548 | 912 | 1095 |
| LPRCVM2 | 1 | 548 | 912 | 1095 |
| LPRCVM3 | 1 | 548 | 912 | 1095 |
| LPRCVM4 | 1 | 548 | 912 | 1095 |

### Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Prolactin requires dose value of stability CVM to fall between ± 10% of assigned dose. Part 2 review limits criteria requires 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 each level then additional data review is conducted using part 2 criteria.

### Traceability:

The IMMULITE Prolactin CVMs are traceable to 3rd IS 84/500. The CVMs are manufactured using qualified materials and measurement procedures.

### Value Assignment:

The IMMULITE® 2000 Prolactin CVMs are 4 level materials which are a subset of 8 level Prolactin calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Prolactin reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. Six levels of commercially available controls and 30 samples (10 normal patients and 20 spiked normal patient samples) were used to validate CVM value assignments.

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

### Expected Values/Target Values/Reference Range:

The Prolactin CVMs were tested on 27 replicates in total comprised of 9 runs and 3 replicates per run, 8 IMMULITE 2000 systems and 4 different reagent kit lots. The CVMs dose values are generated using curve generated by assigned reference calibrators. The CVM values are calculated based on the recovered values for each run on each instrument independently. CVM values are then averaged across all systems. Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mean and ± 2 Standard Deviation (SD). The expected assay range is 0.5 - 150 ng/mL. The target values in Table 3 can be considered as guidelines.

| Analyte target<br>levels | Level | Target<br>Mean<br>(ng/mL) | Standard<br>Deviation<br>(SD) | Guideline ±2SD Range<br>(ng/mL) |
|--------------------------|------------------------------|---------------------------|-------------------------------|---------------------------------|
| | LPRCVM1 | 0.00* | - | 0.00 ≤0.5 |
| | LPRCVM2 | 8.55 | 0.725 | 7.10 10.0 |
| | LPRCVM3 | 42.7 | 3.0 | 36.7 48.7 |
| | LPRCVM4** | 195 | - | - |
| | 80% LPRCVM4 +<br>20% LPRCVM1 | 156* | 12.5 | 131 181 |
| Assay Range | 0.5 - 150 ng/mL | | | |

### Table 3: Analyte Target Range Levels

*Note When CVMs are run by the customer, an actual value below and above the assay range will result when the customer programs the CVMs as calibration verifiers in the instrument software.

If programmed as a patient or control, then the software will give values as < or > the assay lower and upper range.

** Note: LPRCVM4 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

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#### 8. Conclusion:

The IMMULITE® 2000 Prolactin 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 Prolactin 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/13/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an image of an eagle with its wings spread, with three lines extending from the eagle's head.

### DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

May 1, 2014

SIEMENS HEALTHCARE DIAGNOSTICS INC. MR.ERNEST JOSEPH SENIOR MANAGER, REGULATORY AFFAIRS 511 BENEDICT AVE. TARRYTOWN NY 10591

Rc: K140818

Trade/Device Name: IMMULITE® 2000 Free T4 Calibration Verification Material, IMMULITE® 2000 IGF-1 Calibration Verification Material, IMMULITE® 2000 Prolactin Calibration Verification Material Regulation Number: 21 CFR 862,1660 Regulation Name: Quality control material (assayed and unassayed) Regulatory Class: 1, Reserved Product Code: JJX Dated: March 31, 2014 Received: April 1. 2014

Dear Mr. Ernest Joseph:

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

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

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

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Page 2-Mr. Ernest Joseph

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

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (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.lda.gov/MedicalDevices/Safety/ReportalProblem/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 [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely vours.

### Courtney H. Lias -S

Courtney H. Lias. Ph.D.

Director

Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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#### 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 below.

510(k) Number (if known) k140818

#### Device Name

IMMULITE®2000 Free T4 Calibration Material, IMMULITE®2000 IGF-1 Calibration Verification Material, and IMMULITE®2000 Prolactin Calibration Verification Material

#### Indications for Use (Describe)

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

The IMMULITE® IGF-1 Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE IGF-1 assay on the IMMULITE 2000 systems.

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

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

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 FDA USE ONLY

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

### Yung W. Chan -S

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