IMMULITE 2000 DHEA-SO4; THIRD GENERATION TSH AND INTACT PTH CALIBRATION VERIFICATION MATERIAL

K140258 · Siemens Healthcare Diagnostics, Inc. · JJX · Mar 5, 2014 · Clinical Chemistry

Device Facts

• Record ID: K140258
• Device Name: IMMULITE 2000 DHEA-SO4; THIRD GENERATION TSH AND INTACT PTH CALIBRATION VERIFICATION MATERIAL
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: JJX · Clinical Chemistry
• Decision Date: Mar 5, 2014
• Decision: SESE
• Submission Type: Abbreviated
• Regulation: 21 CFR 862.1660
• Device Class: Class 1

Intended Use

The IMMULITE 2000 DHEA-SO4 Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE DHEA-SO4 assay on the IMMULITE 2000 systems. The IMMULITE 2000 Third Generation Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Third Generation TSH assay on the IMMULITE 2000 systems. The IMMULITE 2000 Intact PTH Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Intact PTH assay on the IMMULITE 2000 systems.

Device Story

Calibration verification materials (CVM) for IMMULITE 2000 systems; used to verify assay calibration for DHEA-SO4, Third Generation TSH, and Intact PTH. CVMs consist of four vials of lyophilized analyte in serum/buffer matrix (human or equine). Reconstituted by laboratory personnel; processed on IMMULITE 2000 systems. Output provides recovered dose values compared against assigned target ranges to ensure system performance and calibration accuracy. Used in clinical laboratory settings; results assist healthcare providers in validating assay reliability for patient sample testing.

Clinical Evidence

Bench testing only. Stability validated via real-time shelf life and open-vial studies. Value assignment validated using multiple replicates across systems and reagent lots. Acceptance criteria based on guideline ranges (±8-16% of assigned dose) and control recovery within 2SD of target. No clinical data.

Technological Characteristics

Lyophilized calibration verification material; 4-level set. Matrix: human serum (DHEA-SO4) or equine serum/buffer (TSH, PTH) with preservatives. Storage: ≤-20°C. Stability: 1.5-7 years unopened; 8 hours post-reconstitution. Connectivity: used on IMMULITE 2000 systems. Traceability: DHEA-SO4 (internal material), TSH (WHO 2nd IRP 80/558), PTH (internal material).

Indications for Use

Indicated for in vitro diagnostic use to verify calibration of DHEA-SO4, Third Generation TSH, and Intact PTH 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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MAR - 5 2014

Section 006: 510(k) 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

#### 长140258 The assigned 510(k) Number: _

| 1.<br>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: | Asha Gartland<br>Technical Regulatory Affairs Specialist<br>(914)-524-3257<br>(914)-524-2101<br>[e-mail]<br>January 31, 2014 | | |
| | 2. Device Name<br>Proprietary Name:<br>Measurand:<br>Type of Test: | IMMULITE® 2000 DHEA-SO4 Calibration Verification Material<br>Quality Control materials for IMMULITE® 2000 DHEA-SO4 assay<br>Calibration Verification Material (CVM) for IMMULITE® 2000<br>DHEA-SO4 assay | | |
| | Regulation Section:<br>Classification :<br>Products Code:<br>Panel: | 21 CFR 862.1660, Quality Control Material<br>Class I Reserved<br>JJX - Single (Specified) Analyte Controls (Assayed and Unassayed)<br>Clinical Chemistry (75) | | |
| | 3. Predicate Device Name<br>Predicate 510(k) No: | IMMULITE™ 2000 Insulin Calibration Verification Material (CVM)<br>K133128 | | |
| | 4. Device Description: | The Calibration Verification Material (CVM) contains one set of four<br>vials each 2.0mL after reconstitution. CVM1 contains human serum<br>with preservatives. CVM2, CVM 3 and CVM4 contain various levels<br>of lyophilized DHEA-SO4 in human serum with preservatives. | | |
| | 5. Intended Use:<br>Indication for Use: | See Indications for Use Statement below:<br>The IMMULITE® DHEA-SO4 Calibration Verification Material<br>(CVM) is for in vitro diagnostic use in the verification of calibration<br>of the IMMULITE DHEA-SO4 assay on the IMMULITE 2000<br>systems. | | |

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

- 6. Technological Characteristics and Substantial Equivalence Comparison with Predicate:
For prescription use only

IMMULITE® 2000 Systems

A comparison of the device features, intended use, and other information demonstrates that the IMMULITE® 2000 DHEA-SO4 Calibration Verification Material (CVM) is substantially cquivalent to the predicate device as summarized in Table 1.

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### Table 1: Substantial Equivalence Comparison

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

.

| | DIFFERENCES | |
|---------|------------------------------------------------|-----------------------------------------------|
| | Candidate Device<br>IMMULITE 2000 DHEA-SO4 CVM | Predicate Device<br>IMMULITE 2000 Insulin CVM |
| Analyte | DHEA-SO4 | Insulin |
| Matrix | Human Serum with preservatives | Equine serum with preservatives |

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#### 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.

#### 7.1 Stability Summary:

The stability study was conducted to validate the real-time shelf life and In-Use (Open Component or open vial) claim for the IMMULITE 2000 DHEA-SO4 Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after opening. The IMMULITE® 2000 DHEA-SO4 Calibration Verification Materials are stable up to 7 years when stored at -20°C prior to opening and stable for 8 hours at ambient or room temperature (15-25°C) after reconstitution.

#### 7.1.1 Stability Protocol Summary:

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

| CVM Level | Time-Points (Days) | | | | |
|-----------|--------------------|------|------|------|--|
| LDSCVM1 | 1 | 1642 | 1825 | 2555 | |
| LDSCVM2 | 1 | 1642 | 1825 | 2555 | |
| LDSCVM3 | 1 | 1642 | 1825 | 2555 | |
| LDSCVM4 | 1 | 1642 | 1825 | 2555 | |

#### Table 2: Stability Time Points

For Open Component testing, the results are determined from a 2-point adjustment. Test CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

#### 7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the DHEA-SO4 Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability calibrators/CVM to fall between ±15% of assigned dose for CVM level 2, ±10% of assigned dose for level 3 and ±15% of assigned dose for 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 ±15% for CVM level 2, ±10% for level 3 and ±15% for level 4 then additional data review is conducted using part 2 criteria.

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The acceptance criterion is summarized in Table 3.

| CVM Level | Assigned Dose (µg/dL) | *Guideline Criteria % difference to assigned dose | Acceptable dose range (µg/dL) | **Review Limits |
|-----------|-----------------------|---------------------------------------------------|-------------------------------|-------------------------------------------------|
| LDSCVM1 | 0.00 | Not Applicable | Not Applicable | Controls are within 2SD of target on each curve |
| LDSCVM2 | 46.9 | $\pm$ 15% | 39.9 - 53.9 | |
| LDSCVM3 | 486 | $\pm$ 10% | 437.4 - 534.6 | |
| LDSCVM4 | 1052 | $\pm$ 15% | 894.2 - 1209.8 | |

#### Table 3 Acceptance criteria for stability of IMMULITE 2000 DHEA-SO4 CVM

#### 7.2 Traceability:

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

#### 7.3 Value Assignment:

DHEA-SO4 CVMs are 4 level materials which are a subset of 7 level DHEA-SO4 calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of DHEA-SO4 reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using DHEA-SO4 antigen stock and are traccable to an internal material which has been gravimetrically prepared. Six levels of commercially available controls and 30 normal serum samples were used to validate calibrator/CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The DHEA-SO4 CVMs were tested on 27 replicates in total comprised of 9 runs, 3 replicates per run, on 9 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 cach 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 controls must fall within their target ranges.

#### 7.4 Expected Values/Reference Range:

Each CVM level was tested on 27 replicates in total comprised of 9 runs, 3 replicates per run, on 9 systems and 4 different reagent kit lots. 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 package insert.

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The expected assay range is 1 - 1000 µg/dL. The target values in Table 4 can be considered as guidelines.

| Analyte<br>target levels | CVM Level | Target Mean<br>(µg/dL) | Standard<br>Deviation<br>(SD) | Guideline ±2SD Range<br>(µg/dL) |
|--------------------------|----------------|------------------------|-------------------------------|---------------------------------|
| | CVM1 | 0.00 | - | 0.00 $≤$ 15.00 |
| | CVM2 | 46.9 | 6.1 | 34.7 59.1 |
| | CVM3 | 486 | 43.5 | 399 573 |
| | CVM4 | 1052 | 84 | 884 1220 |
| Assay Range | 1 - 1000 µg/dL | | | |

### Table 4: 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

#### 8. Conclusion:

The IMMULITE® 2000 DHEA-SO4 Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 Insulin Calibration Verification Material. 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 DHEA-SO4 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> | |
|---------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| <b>Mailing Address:</b> | Siemens Healthcare Diagnostics Inc. |
| | 511 Benedict Avenue |
| | Tarrytown, NY 10591 |
| <b>Contact Person:</b> | Asha Gartland |
| | Technical Regulatory Affairs Specialist |
| <b>Phone Number:</b> | (914)-524-3257 |
| <b>Fax Number:</b> | (914)-524-2101 |
| <b>E-mail Address:</b> | [e-mail] |
| <b>Date Prepared:</b> | January 31st, 2014 |
| <b>2. Device Name</b> | |
| <b>Proprietary Name:</b> | IMMULITE® 2000 Third Generation TSH Calibration |
| <b>Measurand:</b> | Verification Material |
| <b>Type of Test:</b> | Quality Control materials for IMMULITE® 2000 Third Generation<br>TSH assay |
| | Calibration Verification Material (CVM) for IMMULITE® 2000<br>Third Generation TSH assay |
| <b>Regulation Section:</b> | 21 CFR 862.1660, Quality Control Material |
| <b>Classification:</b> | Class I Reserved |
| <b>Products Code:</b> | JJX – Single (Specified) Analyte Controls (Assayed and Unassayed) |
| <b>Panel:</b> | Clinical Chemistry (75) |
| | |
| <b>3. Predicate Device Name</b> | IMMULITE® 2000 Insulin Calibration Verification Material (CVM) |
| <b>Predicate 510(k) No:</b> | K133128 |
| <b>4. Device Description:</b> | The Calibration Verification Material (CVM) contains one set of four<br>vials, 3 mL each after reconstitution. CVM 1 contains an equine<br>serum/buffer matrix with preservatives. CVM2. CVM3 and CVM4<br>various levels of lyophilized TSH in an equine serum/buffer matrix<br>with preservatives. |

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5. Intended Use: Indication for Use: See Indications for Use Statement below The IMMULITE® Third Generation TSH Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Third Generation TSH assay on the IMMULITE 2000 systems

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

For prescription use only

IMMULITE® 2000 Systems

6. Technological Characteristics and Substantial Equivalence Comparison with Predicate:

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

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

| SIMILARITIES | | |
|---------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Candidate Device<br>IMMULITE 2000 Third Generation<br>TSH CVM | Predicate Device<br>IMMULITE 2000 Insulin CVM | |
| Intended Use | The IMMULITE® Third Generation<br>TSH Calibration Verification Material<br>(CVM) is for in vitro diagnostic use in<br>the verification of calibration of the<br>IMMULITE Third Generation TSH<br>assay on the IMMULITE 2000 systems | The IMMULITE® Insulin<br>Calibration Verification Material<br>(CVM) is for in vitro diagnostic use<br>in the verification of calibration of the<br>IMMULITE Insulin assay on the<br>IMMULITE 2000 systems |
| Form | Lyophilized | Same |
| Matrix | Equine serum/buffer with preservatives | Same |
| Storage | ≤20°C | Same |
| Stability | Stable unopened until the expiration date | Same |
| Levels | 4 | Same |
| Use | Single Use Only | Same |

| DIFFERENCES | | |
|---------------------------------------------------------------|-----|-----------------------------------------------|
| Candidate Device<br>IMMULITE 2000 Third Generation TSH<br>CVM | | Predicate Device<br>IMMULITE 2000 Insulin CVM |
| Analyte | TSH | Insulin |

#### 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.

#### 7.1 Stability Summary:

The stability study was conducted to validate the real-time shelf life and In-Use (Open Component or open vial) claim for the IMMULITE 2000 Third Generation TSH Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after The IMMULITE 2000 Third Generation TSH Calibration Verification Materials are opening. stable up to 1.5 years when stored frozen at -20°C prior to opening and stable for 8 hours at ambient or room temperature (15-25℃) after reconstitution.

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#### 7.1.1 Stability Protocol Summary:

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

#### Table 2: Stability Time Points

| CVM Level | Time-Points (Days) | | | |
|-----------|--------------------|-----|-----|-----|
| LTSCVM1 | 1 | 182 | 365 | 548 |
| LTSCVM2 | 1 | 182 | 365 | 548 |
| LTSCVM3 | 1 | 182 | 365 | 548 |
| LTSCVM4 | 1 | 182 | 365 | 548 |

For Open Component testing, the results are determined from a 2-point adjustment. Test CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

#### 7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the Third Generation TSH Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of guideline acceptance criteria which require dose value of stability calibrators/CVM to fall between ±10% of assigned dose for CVM level 2, ±12% of assigned dose for level 3 and ±16% of assigned dose for level 4. Part 2 review limits criteria which require dose value of the controls to be within 2SD of the control target value when generated from the stability calibrator curve. If the result is not within acceptable dose range of ±10% for CVM level 2, ±12% for level 3 and ±16% for level 4 then additional data review is conducted using part 2 criteria. The acceptance criterion is summarized in Table 3.

Table 3: Acceptance criteria for stability of IMMULITE 2000 Third Generation TSH CVM

| CVM level | Assigned<br>Dose<br>(µIU/mL) | Guideline Criteria<br>% difference to assigned<br>dose | Acceptable dose range<br>(µIU/mL) | Review<br>Limits |
|-----------|------------------------------|--------------------------------------------------------|-----------------------------------|----------------------------------------------------------|
| LTSCVM1 | 0 | Not Applicable | Not Applicable | Controls are<br>within 2SD<br>of target on<br>each curve |
| LTSCVM2 | 0.58 | ±10% | 0.52 - 0.64 | Controls are<br>within 2SD<br>of target on<br>each curve |
| LTSCVM3 | 4.33 | ±12% | 3.81 - 4.85 | Controls are<br>within 2SD<br>of target on<br>each curve |
| LTSCVM4 | 75 | ±16% | 63.00 - 87.00 | Controls are<br>within 2SD<br>of target on<br>each curve |

7.2 Traceability:

The IMMULITE Third Generation TSH CVMs are traceable to WHO 2nd IRP 80/558. The CVMs are manufactured using qualified materials and measurement procedures.

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#### 7.3 Value Assignment:

Third Generation TSH CVMs are 4 level materials which are a subset of 15 level Third Generation TSH calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Third Generation TSH reagents and two point adjustors. The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared using human TSH antigen spiked in Equine Serum matrix with preservatives. Seven levels of commercially available controls and 30 samples (10 spiked patient samples, 15 spiked normal samples and 5 normal samples were used to validate calibrator/CVM value assignments.

The CVMs are manufactured using qualified materials and measurement procedures. The calibrators/CVMs were tested on 15 replicates in total comprised of 5 runs, 3 replicates per run, on 5 systems and 5 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.

#### 7.4 Expected Values/Reference Range:

Each CVM level was tested on 15 replicates in total comprised of 5 runs, 3 replicates per run, on 5 systems and 5 different reagent kit lots. The Guideline Range (95% confidence interval) for each CVM level was established based on the Target Mcan and ± 2 Standard Deviation (SD). The expected values are provided in the 1MMULITE® 2000 CVM Calibration Verification Material lot-specific package insert The expected assay range is 0.004 - 75 uIU/mL. The target values in Table 4 can be considered as guidelines.

| Analyte target<br>levels | CVM Level | Target<br>(µIU/mL) | Standard<br>Deviation<br>(SD) | Guideline ±2SD<br>Range<br>(µIU/mL) |
|--------------------------|-------------------|--------------------|-------------------------------|-------------------------------------|
| | CVM1 | 0.000 | - | 0.000 0.004 |
| | CVM2 | 0.580 | 0.032 | 0.516 0.644 |
| | CVM3 | 4.33 | 0.26 | 3.81 4.85 |
| | CVM4 | 75.0 | 6.0 | 63.0 87.0 |
| Assay Range | 0.004 - 75 µIU/mL | | | |

| | | Table 4: Target Values |
|--|--|------------------------|
|--|--|------------------------|

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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

#### Conclusion: 8.

The IMMULITE® 2000 Third Generation TSH Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 Insulin Calibration Verification Material. 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 Third Generation TSH Calibration Verification Material does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.

{12}------------------------------------------------

#### 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: _

| 1. Submitter | Siemens Healthcare Diagnostics Inc. |
|--------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Mailing Address: | 511 Benedict Avenue<br>Tarrytown, NY 10591 |
| Contact Person: | Asha Gartland |
| | Technical Regulatory Affairs Specialist |
| Phone Number: | (914)-524-3257 |
| Fax Number: | (914)-524-2101 |
| E-mail Address: | [e-mail] |
| Date Prepared: | January 31, 2014 |
| 2. Device Name | IMMULITE® 2000 Intact PTH Calibration Verification |
| Proprietary Name: | Material |
| Measurand: | Quality Control materials for IMMULITE® 2000 Intact PTH assay |
| Type of Test: | Calibration Verification Material (CVM) for IMMULITE® 2000<br>Intact PTH assay |
| Regulation Section: | 21 CFR 862.1660, Quality Control Material |
| Classification: | Class I Reserved |
| Products Code: | JJX – Single (Specified) Analyte Controls (Assayed and<br>Unassayed) |
| Panel: | Clinical Chemistry (75) |
| 3. Predicate Device Name | IMMULITE® 2000 Insulin Calibration Verification Material<br>(CVM) K133128 |
| Predicate 510(k) No: | |
| 4. Device Description: | The Calibration Verification Material (CVM) contains one set of<br>four vials, with 4 mL for CVM1 and 2 mL each for CVM2, CVM3<br>and CVM4 after reconstitution. CVM1 contains a buffered bovine<br>protein matrix with preservatives. CVM2, CVM3 and CVM4<br>contain various levels of lyophilized synthetic human intact PTH<br>in buffered bovine protein matrix with preservatives. |

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Comparison with Predicate:

See Indications for Use Statement below 5. Intended Use: Indication for Use: The IMMULITE® Intact PTH Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Intact PTH assay on the IMMULITE 2000 systems Special Conditions for For prescription use only Use Statement(s): IMMULITE® 2000 Systems Special Instrument Requirements: A comparison of the device features, intended use, and other 6. Technological information demonstrates that the IMMULITE® 2000 Intact PTH Characteristics and Calibration Verification Material (CVM) is substantially Substantial Equivalence equivalent to the predicate device as summarized in Table 1.

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Table 1: Substantial Equivalence Comparison

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

| DIFFERENCES | | |
|-------------|--------------------------------------------------|-----------------------------------------------|
| | Candidate Device<br>IMMULITE 2000 Intact PTH CVM | Predicate Device<br>IMMULITE 2000 Insulin CVM |
| Analyte | Intact PTH | Insulin |
| Matrix | Buffered Bovine/protein with<br>preservatives | Equine 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.

#### 7.1 Stability Summary:

The real time stability study was conducted to validate shelf life claim and In-Use (Open Component or open vial) claim for the IMMULITE 2000 Intact PTH Calibration Verification Material (CVM) to ensure that it maintains optimal product performance on IMMULITE 2000 platforms throughout the established shelf life of the CVM before and after opening.The IMMULITE® 2000 Intact PTH Calibration Verification Materials (CVMs) are stable up to 2 years when stored at -20℃ prior to opening, and stable for 8 hours at ambient or room temperature (15-25°C) after reconstitution.

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#### 7.1.1 Stability Protocol Summary:

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

| CVM Level | Time-Points (Days) | | | |
|-----------|--------------------|-----|-----|-----|
| LPDCVM1 | 1 | 182 | 365 | 730 |
| LPDCVM2 | 1 | 182 | 365 | 730 |
| LPDCVM3 | 1 | 182 | 365 | 730 |
| LPDCVM4 | 1 | 182 | 365 | 730 |

#### Table 2: Stability Time Points

For Open Component testing, the results are determined from a 2-point adjustment. Test CVMs were tested at 2-hourly intervals for up to 9 hours at ambient or room temperature (15-25°C) conditions.

#### 7.1.2 Stability Acceptance Criteria Summary:

The Acceptance Criteria for the IMMULITE Intact PTH Calibration Verification Material (CVM) are in 2 parts. Part 1 consists of the guideline acceptance criteria which require dose value of stability calibrator/CVM to fall between ±12% of assigned dose for CVM level 2, ±8% of assigned dose for CVM level 3 and ±12% 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 ±12% for level 2, ±8% for level 3 and ±12% for level 4, then additional data review is conducted using part 2 criteria.

The acceptance criterion is summarized in Table 3.

Table 3: Acceptance criteria for stability of IMMULITE 2000 Intact PTH CVM

| CVM level | Assigned<br>Dose<br>(pg/mL) | *Guideline Criteria<br>% difference to<br>assigned dose | Acceptable dose<br>range (pg/mL) | Review<br>Limits |
|-----------|-----------------------------|---------------------------------------------------------|----------------------------------|------------------|
| LPPCVM1 | 0.00 | Not Applicable | Not Applicable | Controls are |
| LPPCVM2 | 15.2 | ±12% | 13.4 - 17.0 | within 2SD |
| LPPCVM3 | 154 | ±8% | 141.7 - 166.3 | of target on |
| LPPCVM4 | 3784 | ±12% | 3329.9 - 4238.1 | each curve |

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#### 7.2 Traceability:

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

#### 7.3 Value Assignment:

Intact PTH CVMs are 4 level materials which are a subset of 9 level Intact PTH calibrators. Calibrators are not commercialized but are used internally during manufacture and release testing of Intact PTH reagents and two point adjustors.

The IMMULITE calibrators and therefore CVMs are value assigned using assigned reference calibrators. The assigned reference calibrators are prepared synthetic Human Intact PTH (1-84) spiked in the buffered bovine protein matrix. Two levels of commercially available controls and 88 samples (32 EDTA plasma, 32 serum, 12 EDTA dialysis samples and serum dialysis samples) are used to validate calibrator/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, 7 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.

#### 7.4 Expected Values/Reference Range:

Each CVM level was tested on 27 replicates in total comprised of 9 runs, 7 systems and 3 different reagent kit lots. 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 lotspecific package insert. The expected assay range is 1-2500 pg/mL. The target values in Table 4 can be considered as guidelines.

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Table 4: Target Values

| Analyte target<br>levels | CVM Level | Target Mean<br>(pg/mL) | Standard<br>Deviation<br>(SD) | Guideline ±2SD Range<br>(pg/mL) |
|--------------------------|--------------------------|------------------------|-------------------------------|---------------------------------|
| | CVM1 | 0.00 | - | 0.00 - 3.00 |
| | CVM2 | 20.4 | 1.35 | 17.7 - 23.1 |
| | CVM3 | 167 | 15.0 | 137 - 197 |
| | CVM4 | 5176 | - | - |
| | (50% CVM1 +<br>50% CVM4) | 2588 | 155.5 | 2277 - 2899 |
| Assay Range | 1-2500 pg/mL | | | |

CVM4 requires dilution to ensure the target value is within +10% of the top of the reportable range of the assay

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

Standard/Guidance Documents Referenced:

- CEN 13640 Stability Testing of In Vitro Diagnostic Reagents .
- Guidance for Industry Abbreviated 510(k) Submissions for In Vitro Diagnostic . Calibrators
- Guidance for Industry and FDA Staff Assayed and 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 Intact PTH Calibration Verification Material is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the FDA cleared IMMULITE® 2000 Insulin Calibration Verification Material 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 Intact PTH 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/18/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized symbol that resembles three overlapping, curved shapes, possibly representing human figures or abstract forms. The logo is black and white and appears to be a scanned or printed image.

Food and Drug Administration 1 0903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002 March 5, 2014

SIEMENS HEALTHCARE DIAGNOSTICS, INC. ASHA GARTLAND TECHNICAL REGULATORY AFFAIRS SPECIALIST 511 BENEDICT AVENUE TARRYTOWN NY 10591

Re: K140258

Trade/Device Name: IMMULITE® 2000 DHEA-SO4 Calibration Verification Material, IMMULITE® 2000 Third Generation TSH Calibration Verification Material, IMMULITE® 2000 Intact PTH Calibration Verification Material Regulation Number: 21 CFR 862.1660 Regulation Name: Quality Control Material (assayed and unassayed) Regulatory Class: I, Reserved Product Code: JJX Dated: January 31, 2014 Received: February 3, 2014

Dear Asha Gartland:

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

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [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/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 Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

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

510(k) Number (if known) k140258

#### Device Name

MMULITE 2000 DHEA-SO4 Calibration Verification Material, MMULITE 2000 Third Generation TSH Calibration Verification Material, MMULITE 2000 Intact PTH Calibration Verification Material,

Indications for Use (Describe)

The IMMULITE 2000 DHEA-SO4 Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE DHEA-SO4 assay on the IMMULITE 2000 systems.

The IMMULITE 2000 Third Generation Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Third Generation TSH assay on the IMMULITE 2000 systems.

The IMMULITE 2000 Intact PTH Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Intact PTH 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)

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FORM FDA 3881 (1/14)

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