ELECSYS HE4, ELECSYS HE4 CALSET, ELECSYS PRECICONTROL HE4, ELECSYS HE4 CALCHECK 5

K112624 · Roche Diagnostics · OIU · Sep 10, 2012 · Immunology

Device Facts

• Record ID: K112624
• Device Name: ELECSYS HE4, ELECSYS HE4 CALSET, ELECSYS PRECICONTROL HE4, ELECSYS HE4 CALCHECK 5
• Applicant: Roche Diagnostics
• Product Code: OIU · Immunology
• Decision Date: Sep 10, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

The Elecsys HE4 assay is an immunoassay for the quantitative determination of HE4 in human serum and plasma. The assay is used as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer. Serial testing for patient HE4 assay values should be used in conjunction with other clinical findings used for monitoring ovarian cancer. The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.

Device Story

The Elecsys HE4 assay is an in vitro diagnostic immunoassay for the quantitative measurement of HE4 antigen in human serum and plasma. It utilizes electrochemiluminescence immunoassay (ECLIA) technology on Roche Elecsys and cobas e immunoassay analyzers. The assay is a sandwich immunoassay using a biotinylated monoclonal murine anti-HE4 IgG antibody for capture and a ruthenium-labeled monoclonal murine anti-HE4 IgG antibody for signal detection. The device is operated by laboratory professionals in clinical settings. The output is a quantitative HE4 concentration value (pmol/L). Healthcare providers use serial measurements of HE4 levels to monitor for disease recurrence or progression in patients with epithelial ovarian cancer, integrating these results with other clinical findings to inform patient management decisions.

Clinical Evidence

Clinical study of 80 female EOC patients (493 total observations). Evaluated % change in HE4 levels against physician-determined disease status (NED, stable, responding, progressive). AUC for ROC curve was 0.699 (95% CI: 0.630-0.767). At 20% change threshold, sensitivity was 46.9% and specificity was 84.0%. Performance was comparable to predicate ARCHITECT HE4.

Technological Characteristics

Two-step sandwich immunoassay. Reagents: biotinylated mouse monoclonal anti-HE4 antibody, ruthenium-labeled monoclonal anti-HE4 antibody, streptavidin-coated microparticles. Energy: electrochemiluminescence. Sample volume: 10 μL. Measuring range: 20–1500 pmol/L. Platform: Elecsys/cobas e analyzers. Calibration: 2-point calibration with master curve. Sterilization: not applicable (reagents).

Indications for Use

Indicated for monitoring recurrence or progressive disease in patients with epithelial ovarian cancer. Used as an aid in conjunction with other clinical findings.

Regulatory Classification

Identification

A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.

Special Controls

*Classification.* Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.

Predicate Devices

• Abbott Architect HE4 (K093957)

Submission Summary (Full Text)

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# K112624

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## Comparison of Assays—Similarities and Differences

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| Immunoassay Comparison | | |
|--------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect<br>HE4 (K093957) |
| General Assay Features | | |
| Intended<br>Use/<br>Indications<br>for Use | The Elecsys HE4 assay is an<br>immunoassay for the quantitative<br>determination of HE4 in human serum<br>and plasma. The assay is used as an aid<br>in monitoring the recurrence or<br>progressive disease in patients with<br>epithelial ovarian cancer. Serial testing<br>for patient HE4 assay values should be<br>used in conjunction with other clinical<br>findings used for monitoring ovarian<br>cancer.<br><br>The electrochemiluminescence<br>immunoassay "ECLIA" is intended for<br>use on Elecsys and cobas e immunoassay<br>analyzers. | The ARCHITECT HE4 assay is a<br>chemiluminescent microparticle<br>immunoassay (CMIA) for the quantitative<br>determination of the HE4 antigen in<br>human serum.<br><br>The assay is to be used as an aid in<br>monitoring recurrence or progressive<br>disease in patients with epithelial ovarian<br>cancer. Serial testing for patient HE4<br>assay values should be used in<br>conjunction with other clinical methods<br>used for monitoring epithelial ovarian<br>cancer. |
| Assay<br>Protocol | Quantitative sandwich immunoassay | Quantitative chemiluminescent<br>microparticle immunometric assay |
| Detection<br>Protocol | Electrochemiluminescence | Chemiluminescence |
| Applications | 18 minute application | Not reported |

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Comparison of Assays—Similarities and Differences, continued

| Immunoassay Comparison | | |
|------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect HE4 (K093957) |
| General Assay Features | | |
| Instrument<br>Platform | Elecsys 2010 and MODULAR<br>ANALYTICS E170; Cobas e 411, cobas e<br>601 and cobas e 602 | ARCHITECT i 2000, i 2000SR, i 1000 and i1000SR. |
| Sample<br>Volume | 10 μL | 75 μL for first test plus 25 μL for each<br>additional test from the same sample cup.<br><br>≤ 3 hours on board: 150 μL for the first<br>test plus 25 μL for each additional test<br>from the same sample cup. |
| Sample<br>Type | Human serum and plasma treated with<br>K2-EDTA, K3-EDTA or lithium heparin. | Human serum |
| Reagents | The Elecsys HE4 assay is a sandwich<br>immunoassay which includes a<br>biotinylated monoclonal, murine HE4-<br>specific IgG antibody as capture and a<br>ruthenium labeled monoclonal, murine<br>HE4-specific IgG antibody as signal. | The Abbott ARCHITECT HE4 is a two-<br>step immunoassay for the quantitative<br>determination of HE4 antigen in human<br>serum using CMIA technology with<br>flexible assay protocols, referred to as<br>Chemiflex. |
| Calibrator | Elecsys HE4 CalSet, 2 levels | Abbott ARCHITECT HE4 Calibrators, 6<br>levels |

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| Feature | Elecsys HE4 Assay | Predicate Devices: Abbott Architect HE4 (K093957) |
|-------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| General Assay Features | | |
| Calibration<br>Interval | Calibration must be performed once per<br>reagent lot using fresh reagent (i.e. not<br>more than 24 hours since the reagent kit<br>was registered on the analyzer).<br>Renewed calibration is recommended as<br>follows:<br>After 28 days when using the<br>same reagent lot. After 7 days (when using the<br>same reagent kit on the<br>analyzer). As required: e.g. quality control<br>findings outside the specified<br>limits | Once an ARCHITECT HE4 calibration is<br>accepted and stored, all subsequent<br>samples may be tested without further<br>calibration unless one or more of the<br>following occur:<br>A reagent kit with a new lot<br>number is used Controls are out of range |
| Controls | Elecsys HE4 PreciControl | Abbott ARCHITECT HE4 Controls |

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and the comments of the comments of

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| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect HE4 (K093957) |
|--------------------------------|-----------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| General assay features | | |
| Traceability / Standardization | The Elecsys HE4 Assay has been standardized against the HE4 EIA method from Fujirebio Diagnostics, Inc. | Not reported |
| Reagent Stability | Unopened at 2-8 °C—up to stated expiration date<br>After opening at 2-8 °C—12 weeks<br>On the analyzers—28 days | The ARCHITECT HE4 Reagent Kit must be stored at 2-8°C in an upright position and may be used immediately after removal from 2-8°C.<br><br>When stored and handled as directed, the reagents are stable until the expiration date.<br><br>The ARCHITECT HE4 Reagent Kit may be stored on board the ARCHITECT <i>i</i> System for a maximum of 30 days.<br><br>Reagents may be stored on or off the ARCHITECT <i>i</i> system. If reagents are removed from the system, store them at 2-8°C (with septums and replacement caps) in an upright position. For reagents stored off the system, it is recommended that they be stored in their original trays and boxes to ensure they remain upright. If the microparticle bottle does not remain upright (with a septum installed) while in refrigerated storage off the system, |

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| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect<br>HE4 (K093957) |
|-------------------------------------|----------------------------------------------------|-----------------------------------------------------|
| Labeled Performance Characteristics | | |
| Measuring Range | 15-1,5000 pmol/L | 20-1,500 pmol/L |
| Precision | Elecsys 2010/ cobas e 411: | On the ARCHITECT i 2000SR System: |
| | Within-run (will be labeled Repeatability)<br>n=84 | Within-run<br>n=80 |
| | 1.8% CV @ 25.3 pmol/L | 3.0% CV @ 49.0 pmol/L |
| | 1.4% CV @ 45.7 pmol/L | 2.2% CV @ 174.4 pmol/L |
| | 1.8% CV @ 53.7 pmol/L | 2.4% CV @ 687.3 pmol/L |
| | 1.6% CV @ 142.0 pmol/L | 3.1% CV @ 38.4 pmol/L |
| | 1.6% CV @ 345.0 pmol/L | 2.9% CV @ 189.7 pmol/L |
| | 1.5% CV @ 779.0 pmol/L | 2.9% CV @ 1114.7 pmol/L |
| | 1.3% CV @ 1437.0 pmol/L | |
| | Total (will be labeled Intermediate) | Total |
| | 3.7% CV @ 25.3 pmol/L | 3.3% CV @ 49.0 pmol/L |
| | 4.2% CV @ 45.7 pmol/L | 3.1% CV @ 174.4 pmol/L |
| | 4.2% CV @ 53.7 pmol/L | 3.3% CV @ 687.3 pmol/L |
| | 4.3% CV @ 142.0 pmol/L | 3.8% CV @ 38.4 pmol/L |
| | 3.4% CV @ 345.0 pmol/L | 3.1% CV @ 189.7 pmol/L |
| | 2.7% CV @ 779.0 pmol/L | 3.3% CV @ 1114.7 pmol/L |
| | 4.2% CV @ 1437.0 pmol/L | |

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## Comparison of Assays—Similarities and Differences, continued

| Immunoassay Comparison | | | | | | | | |
|-------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------|--|--|--|--|--|------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect HE4 (K093957) | | | | | | |
| Labeled Performance Characteristics | | | | | | | | |
| Analytical<br>Sensitivity | On the e411:<br>Limit of Blank (LoB) 5.0 pmol/L<br>Limit of Detection (LoD) 15.0 pmol/L<br>Limit of Quantitation (LoQ) 20.0 pmol/L<br>with a total allowable error of 30% | Limit of Blank: 0.1 pmol/L<br>Limit of Detection: ≤ 15 pmol/L<br>Functional Sensitivity: 20 pmol/L | | | | | | |
| Analytical<br>Specificity | Proteins (WFDC family) Reactivity Elafin/ SKALP<br>at 54,500 pmol/L 0.025% SLPI at 20,833<br>pmol/L 0.088 | | | | | | | No cross reactivity of above +/- LoD (<15 pmol/L) was seen with the following interferents tested:<br>• CA 125<br>• CA 15-3<br>• CA 19-9<br>• CEA<br>• AFP |
| Hook Effect | There is no high-dose hook effect at HE4 concentrations up to 40,000 pmol/L. | There is no high-dose hook effect at HE4 concentrations up to 83,000 pmol/L. | | | | | | |

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| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect HE4 (K093957) | | | | | | | | | |
|-------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--|--|--|--|--|--|
| Labeled Performance Characteristics | | | | | | | | | | | |
| Limitations | The assay is unaffected by: | The assay is unaffected by: | | | | | | | | | |
| | Hemoglobin ≤ 1.0 g/dL Bilirubin up ≤ 66 mg/dL Triglycerides ≤ 2,000 mg/dL Biotin ≤ 50 ng/mL Rheumatoid Factor < 1,500 IU/mL HAMA < 805 ng/mL IgG ≤ 70 g/L In vitro tests were performed on 52 commonly used pharmaceuticals. No interference with the assay was found. In rare cases, interference due to extremely high titers of antibodies to analyte-specific antibodies (such as HAMA), streptavidin or ruthenium can occur. These effects are minimized by suitable test design. | Hemoglobin 500 mg/dL Bilirubin up 20 mg/dL Triglycerides 3000 mg/dL Low protein 3 g/dL High protein 12 g/dL Six specimens positive for HAMA and six specimens positive for Rheumatoid Factor (RF) were evaluated at the indicated interferent concentration ranges. The data are summarized in the following table. Clinical Condition Interferent Concentration Range Mean % Recovery HAMA 45-155 ng/mL 102 RF 21-445 IU/mL 103 | | | | | | | | | |

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| Immunoassay Comparison | | | | | | | | | | |
|----------------------------------------------------------|-----------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|--|--|--|--|--|--|
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect HE4 (K093957) | | | | | | | | |
| Labeled Performance Characteristics | | | | | | | | | | |
| Clinical Sensitivity and Specificity | See below | See below | | | | | | | | |
| Internal Method Comparison (cobas e 601 vs. cobas e 411) | n = 131<br>Min = 17.0 pmol/L<br>Max = 1405.0 pmol/L | Passing/Bablok Linear Regression Slope<br>1.01<br>(1.00-1.02) 1.00<br>(0.994-1.01) Intercept<br>-0.435<br>(-1.03-0.365) 2.29<br>(1.01-3.56) Tau/r<br>0.979 0.999 | | | | | | | | |

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## Clinical Sensitivity and Specificity Elecsys HE4

| Percent<br>Change<br>in HE4 | Sensitivity<br>(%)<br>(n/N) | Lower CI<br>(95%) for<br>Sensitivity | Upper CI<br>(95%) for<br>Sensitivity | Specificity (%)<br>(n/N) | Lower CI<br>(95%) for<br>Specificity | Upper CI<br>(95%) for<br>Specificity |
|-----------------------------|-----------------------------|--------------------------------------|--------------------------------------|--------------------------|--------------------------------------|--------------------------------------|
| 0 | 69.14 (56/81) | 57.61 | 80.88 | 57.83<br>(192/332) | 52.35 | 63.44 |
| 5 | 62.96 (51/81) | 50.63 | 75.61 | 68.07<br>(226/332) | 62.71 | 73.08 |
| 10 . | 54.32 (44/81) | 42.13 | 66.67 | 74.70<br>(248/332) | 69.47 | 79.32 |
| 14 | 50.62 (41/81) | 39.34 | 62.09 | 77.41<br>(257/332) | 72.52 | 81.76 |
| 15 | 49.38 (40/81) | 38.28 | 60.48 | 78.31<br>(260/332) | 73.68 | 82.51 |
| 20 | 46.91 (38/81) | 35.44 | 58.44 | 84.04<br>(279/332) | 80.12 | 87.76 |
| 25 | 39.51 (32/81) | 28.84 | 51.23 | 87.05<br>(289/332) | 83.56 | 90.34 |
| 50 | 24.69 (20/81) | 16.00 | 34.52 | 95.78<br>(318/332) | 93.65 | 97.64 |
| 75 | 17.28 (14/81) | 9.20 | 26.75 | 97.59<br>(324/332) | 95.92 | 99.02 |
| 100 | 14.81 (12/81) | 7.50 | 23.94 | 97.89<br>(325/332) | 96.29 | 99.19 |

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| Percent<br>Change in<br>HE4 | Sensitivity<br>(%) | Specificity<br>(%) | PPV (%) | NPV (%) |
|-----------------------------|--------------------|--------------------|---------|---------|
| 10 | 57 | 75 | 40 | 85 |
| 14 | 54a | 79b | 43c | 85d |
| 20 | 48 | 84 | 48 | 85 |
| 25 | 41 | 87 | 49 | 83 |
| 50 | 31 | 94 | 60 | 82 |
| 75 | 21 | 97 | 66 | 80 |
| 100 | 18 | 98 | 69 | 80 |

#### Clinical Sensitivity and Specificity ARCHITECT HE4

- Sensitivity is 100 X (number of sequential pairs with a ≥ 14% increase in HE4 concentration a. from patients with disease progression/total number of sequential pairs from patients with disease progression)
- b. Specificity is 100 X (number of sequential pairs with < 14% increase in HE4 concentration from patients without disease progression/total number of sequential pairs from patients without disease progression)
- PPV = 100 X(number of sequential pairs with ≥ 14% increase in HE4 concentration from c. patients with discase progression/total number of sequential pairs with a ≥ 14% increase in HE4 concentration)
- d. `NPV = 100 X (number of sequential pairs with < 14% increase in HE4 concentration from patients without disease progression/total number of sequential pairs with a < 14% increase in HE4 concentration)

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#### Comparison of Calibrator Materials

| Characteristic | CalSet for Elecsys HE4 Assay | Predicate Device: Elecsys hGH CalSet (K103221) |
|--------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Elecsys HE4 CalSet is used for calibrating the quantitative Elecsys HE4 assay on the Elecsys and cobas e immunoassay analyzers. | Elecsys hGH CalSet is used for calibrating the quantitative Elecsys hGH assay on the Elecsys and cobas e immunoassay analyzers. |
| Levels | Two | Same |
| Matrix | Equine serum | Human serum |
| Format | Lyophilized | Same |
| Stability | Unopened:<br>• Store at 2 - 8°C up to the stated expiration date.<br>After reconstitution:<br>• At 2 - 8°C: 7 days.<br>• At -20°C: 8 weeks (freeze only once).<br>• On Elecsys 2010/cobas e 411 at 20 - 25°C: Up to 5 hours.<br>• On MODULAR ANALYTICS E170/cobas e 601 and 602: Use only once. | Unopened:<br>• Store at 2 - 8°C up to the stated expiration date.<br>After reconstitution:<br>• At 2 - 8°C: 7 days<br>• At -20°C: 28 days (freeze only once).<br>• On Elecsys 2010/cobas e 411 at 20 - 25°C: Up to 5 hours.<br>On MODULAR ANALYTICS E170/cobas e 601: Use only once. |
| Handling | Dissolve the contents of one bottle carefully by adding exactly 1.0 mL of distilled water and allow to stand closed for 15 minutes to reconstitute. Mix carefully, avoiding the formation of foam. Transfer the reconstituted calibrator into the empty labeled snap-cap bottles supplied. | Dissolve carefully the contents of one bottle by adding exactly 1.0 mL of distilled or deionized water and allow to stand closed for 15 minutes to reconstitute. Mix carefully, avoiding the formation of foam. Transfer the reconstituted calibrator into the empty labeled snap-cap bottle supplied. |
| Characteristic | Elecsys HE4 PreciControl | Predicate Device:<br>Elecsys PreciControl<br>Multimarker (K102157) |
| Intended Use | Elecsys PreciControl HE4 is used for<br>quality control of Elecsys HE4 on the<br>Elecsys and cobas e immunoassay<br>analyzers. | Elecsys PreciControl Multimarker is<br>used for quality control of specified<br>Elecsys immunoassays on the Elecsys<br>and cobas e immunoassay analyzers. |
| Levels | Two | Same |
| Format | Lyophilized | Same |
| Matrix | Human serum | Same |
| Analyte<br>Concentration | Approximately 50 and 400 pmol/L | C-Peptide (synthetic): Approximately<br>2 and 10 ng/mL.<br>Insulin (human recombinant from<br>yeast): Approximately 25 and 80<br>μU/mL.<br>ACTH (synthetic): Approximately 50<br>and 1,000 pg/mL.<br>hGH (human recombinant from E.<br>coli): Approximately 1 and 10 ng/mL. |
| Stability | Unopened:<br>• Store at 2-8°C up to the stated<br>expiration date.<br><br>Reconstituted:<br>• 2 - 8°C: 14 days<br>• -20°C: 4 weeks (freeze only once)<br>• On the analyzers at 20-25°C: up to 5<br>hours<br>At 20-25°C: 24 hours | Unopened:<br>• Store at 2-8°C up to the stated<br>expiration date.<br><br>Reconstituted:<br>• 2 - 8°C: 72 hours<br>• -20°C: 31 days (freeze only once)<br>• On the analyzers at 20-25°C: up to<br>5 hours |
| Handling | Carefully dissolve the contents of one<br>bottle by adding exactly 1.0 mL of<br>distilled or deionized water and allow to<br>stand closed for 15 minutes to<br>reconstitute. Mix carefully, avoiding the<br>formation of foam. Transfer the<br>reconstituted control into the empty,<br>labeled snap-cap bottles supplied or<br>freeze aliquots in additional snap-cap<br>bottles (ControlSet Vials). Attach the<br>supplied labels to these bottles. Perform<br>only one control procedure per aliquot. | Dissolve carefully the contents of one<br>bottle by adding exactly 2.0 mL of<br>distilled or deionized water and allow<br>to stand closed for 30 minutes to<br>reconstitute. Mix carefully, avoiding<br>the formation of foam. Transfer the<br>reconstituted control into empty,<br>labeled snap-cap bottles supplied<br>(ControlSet Vials) and freeze aliquots<br>immediately in additional ControlSet<br>Vials. Attach the supplied labels to<br>these additional bottles. Perform only<br>one control procedure per aliquot. |
| Characteristic | Elecsys HE4 CalCheck 5 | Predicate Device:<br>Elecsys DHEA-S CalCheck 5<br>(K103402) |
| Intended Use | The Elecsys HE4 CalCheck 5 is an<br>assayed control for use in calibration<br>verification and for use in the verification<br>of the assay range established by the<br>Elecsys HE4 reagent on the indicated<br>Elecsys and cobas e immunoassay<br>analyzers. For In Vitro Diagnostic Use<br>Only. | The Elecsys DHEA-S CalCheck 5 is an<br>assayed control for use in calibration<br>verification and for use in the<br>verification of the assay range<br>established by the Elecsys DHEA-S<br>reagent on the indicated Elecsys and<br>cobas e immunoassay analyzers. |
| Analyte | HE4 | DHEA-S |
| Levels | Five | Same |
| Matrix | Equine serum | Human serum |
| Format | Lyophilized | Same |
| Handling | Reconstitute Check 1, Check 2, Check 3,<br>Check 4 and Check 5 with exactly 1.0 mL<br>distilled or deionized water. Allow to<br>stand closed for 15 minutes, then mix<br>gently by inversion. | Same |
| Stability | Unopened:<br>● Store at 2-8 °C up to the stated<br>expiration date.<br>Reconstituted:<br>● 20-25 °C: 5 hours | Unopened:<br>● Store at 2-8 °C up to the stated<br>expiration date.<br>Reconstituted:<br>● 20-25 °C: 4 hours |

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## Comparison of PreciControl Materials

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## Comparison of CalCheck 5 Materials

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The Elecsys HE4 Immunoassay was evaluated for several characteristics, Evaluations including precision, limit of quantitation, linearity, method comparison, Summary interfering substances, and calibration stability.

> The Elecsys HE4 CalSet, Elecsys PreciControl HE4 and HE4 CalCheck 5 were evaluated for value assignment and stability.

> In addition, the Elecsys HE4 Immunoassays were evaluated in the clinical setting, completing a method comparison with clinically characterized samples, and measuring HE4 over time in subjects with ovarian cancer.

Confidentiality

Roche Diagnostics Corporation requests that the FDA not disclose the nature or existence of the premarket notification until the substantial equivalence decision has been reached.

Closing

We trust that the information provided in this Premarket Notification [510(k)] will support a determination of substantial equivalence for the Elecsys HE4 Test System.

If you should have questions or require further information, please do not hesitate to contact this office.

· Phone: [phone]

· FAX: [phone]

[e-mail]

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Image /page/14/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features the department's name encircling a stylized eagle emblem. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the top half of the circle. The eagle is depicted with its wings spread, symbolizing the department's mission to protect the health of all Americans.

10903 New Hampshire Avenue Silver Spring, MD 20993

Roche Diagnostics c/o Dr. Jane Phillips Regulatory Program Manager 9115 Hague Road Indianapolis, IN 46250

Re: k112624

Trade/Device Name: Elecsys HE4 Assay Elecsys HE4 CalSet Elecsys PreciControl HE4 Elecsys HE4 CalCheck 5

Regulation Number: 21 CFR §866.6010

Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: OIU, JIT, JJX Dated: September 14, 2012 Received: September 17, 2012

Dear Dr. Phillips:

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.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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

OCT 10 2012

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#### Page 2 - Dr. Jane Phillips

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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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/cdrh/industry/support/index.html.

Sincerely yours,

Reena Philip

Maria M. Chan, Ph. D 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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510(k) Number (if known): ___K112624

Device Name: Elecsys HE4 Assay

Indications for Use:

The Elecsys HE4 assay is an immunoassay for the quantitative determination of HE4 in human serum and plasma. The assay is used as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer. Serial testing for patient HE4 assay values should be used in conjunction with other clinical findings used for monitoring ovarian cancer.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on Elecsys and cobas e immunoassay analyzers.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K i i 2 624

Page 1 of

{17}------------------------------------------------

510(k) Number (if known): ___K112624

Elecsys HE4 CalSet Device Name:

Indications for Use: Elecsys HE4 CalSet is used for calibrating the quantitative Elecsys HE4 assay on the Elecsys and cobas e immunoassay analyzers.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

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

#### (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) k112624

Page 1 of

{18}------------------------------------------------

510(k) Number (if known):

Elecsys PreciControl HE4 Device Name:

Indications for Use: Elecsys PreciControl HE4 is used for quality control of the Elecsys HE4 immunoassay on Elecsys and cobas e immunoassay analyzers.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

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

#### (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

O 0

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K112624

Page 1 of l

{19}------------------------------------------------

510(k) Number (if known): ___K112624

Elecsys HE4 CalCheck 5 Device Name:

Indications for Use: The Elecsys HE4 CalCheck 5 is an assayed control for use in calibration verification and for use in the verification of the assay range established by the Elecsys HE4 reagent on the indicated Elecsys and cobas e immunoassay analyzers. For In Vitro Diagnostic Use Only.

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K112624