(368 days)
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 the 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.
The Elecsys HE4 assay is a sandwich immunoassay which includes a biotinylated monoclonal, murine HE4-specific IgG antibody as capture and a ruthenium labeled monoclonal, murine HE4-specific IgG antibody as signal.
Here's a breakdown of the acceptance criteria and study information for the Elecsys HE4 Assay, based on the provided text.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Elecsys HE4 Assay are primarily demonstrated through comparison with a predicate device (Abbott Architect HE4) and through its own labeled performance characteristics. The key performance metrics are listed below:
| Feature | Acceptance Criteria (Implied / Predicate Device Performance) | Reported Elecsys HE4 Assay Performance |
|---|---|---|
| Measuring Range | 20-1,500 pmol/L (Predicate) | 15-1,5000 pmol/L |
| Precision (Within-run) | 3.0% CV @ 49.0 pmol/L (Predicate) | 1.8% CV @ 25.3 pmol/L |
| 2.2% CV @ 174.4 pmol/L (Predicate) | 1.4% CV @ 45.7 pmol/L | |
| 2.4% CV @ 687.3 pmol/L (Predicate) | 1.8% CV @ 53.7 pmol/L | |
| 3.1% CV @ 38.4 pmol/L (Predicate) | 1.6% CV @ 142.0 pmol/L | |
| 2.9% CV @ 189.7 pmol/L (Predicate) | 1.6% CV @ 345.0 pmol/L | |
| 2.9% CV @ 1114.7 pmol/L (Predicate) | 1.5% CV @ 779.0 pmol/L | |
| (Not reported for predicate for 1437.0 pmol/L) | 1.3% CV @ 1437.0 pmol/L | |
| Precision (Total) | 3.3% CV @ 49.0 pmol/L (Predicate) | 3.7% CV @ 25.3 pmol/L |
| 3.1% CV @ 174.4 pmol/L (Predicate) | 4.2% CV @ 45.7 pmol/L | |
| 3.3% CV @ 687.3 pmol/L (Predicate) | 4.2% CV @ 53.7 pmol/L | |
| 3.8% CV @ 38.4 pmol/L (Predicate) | 4.3% CV @ 142.0 pmol/L | |
| 3.1% CV @ 189.7 pmol/L (Predicate) | 3.4% CV @ 345.0 pmol/L | |
| 3.3% CV @ 1114.7 pmol/L (Predicate) | 2.7% CV @ 779.0 pmol/L | |
| (Not reported for predicate for 1437.0 pmol/L) | 4.2% CV @ 1437.0 pmol/L | |
| Analytical Sensitivity | Limit of Detection: ≤ 15 pmol/L (Predicate) | Limit of Blank (LoB) 5.0 pmol/L; Limit of Detection (LoD) 15.0 pmol/L; Limit of Quantitation (LoQ) 20.0 pmol/L with a total allowable error of 30% |
| Analytical Specificity | No cross reactivity with CA 125, CA 15-3, CA 19-9, CEA, AFP (Predicate) | Proteins (WFDC family) Reactivity: Elafin/SKALP at 54,500 pmol/L 0.025%; SLPI at 20,833 pmol/L 0.088 |
| Hook Effect | No high-dose hook effect up to 83,000 pmol/L (Predicate) | No high-dose hook effect at HE4 concentrations up to 40,000 pmol/L |
| Interfering Substances | Unaffected by various levels of Hemoglobin, Bilirubin, Triglycerides, HAMA, RF, etc. (Predicate) | Unaffected by various levels of Hemoglobin, Bilirubin, Triglycerides, Biotin, Rheumatoid Factor, HAMA, IgG. (Specific concentrations listed) |
| Clinical Performance (Sensitivity at 14% change) | 54% (Predicate) | 50.62% (41/81) |
| Clinical Performance (Specificity at 14% change) | 79% (Predicate) | 77.41% (257/332) |
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Study for Sensitivity and Specificity:
- Test Set Size: 81 sequential pairs from patients with disease progression (for sensitivity) and 332 sequential pairs from patients without disease progression (for specificity).
- Data Provenance: The document does not explicitly state the country of origin. It notes "clinically characterized samples" and "subjects with ovarian cancer" but does not specify if the data is retrospective or prospective. Given the nature of monitoring recurrence, it is highly likely to be prospective data collected over time.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not provide information on the number or qualifications of experts used to establish the ground truth for the clinical test set (i.e., whether patients had disease progression or not). The ground truth appears to be based on "clinically characterized samples" which would likely involve standard clinical assessments, possibly including imaging, biopsy results, and physician evaluations, but details are not given.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of disease progression or non-progression for the clinical test set. The term "clinically characterized samples" suggests that the disease status was determined through routine clinical diagnosis and monitoring processes.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not conducted. This device is an in-vitro diagnostic (IVD) assay that directly measures a biomarker, not an imaging or interpretive AI device where human reader improvement would be relevant.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented represent standalone performance of the Elecsys HE4 Assay (an algorithm/assay only) without human-in-the-loop performance. The device provides a quantitative measurement of HE4.
7. The Type of Ground Truth Used
The ground truth used for the clinical sensitivity and specificity evaluation appears to be clinical outcome data (disease progression vs. no disease progression) derived from "clinically characterized samples."
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning, as this is an immunoassay and not an AI/ML-based device that would typically have a separate training phase with a distinct training set. The data presented for performance characteristics (precision, linearity, sensitivity, specificity) are related to the assay's analytical and clinical validation.
9. How the Ground Truth for the Training Set was Established
As this is an immunoassay, the concept of a "training set" as understood in AI/ML is not directly applicable. The assay's development and optimization would rely on established biochemical and analytical methods, with calibration against known standards. The "standardization" of the Elecsys HE4 Assay against the HE4 EIA method from Fujirebio Diagnostics, Inc., serves a similar purpose to establishing a foundational "ground truth" for the assay's measurements.
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K112624
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OCT 1 0 2012
Comparison of Assays—Similarities and Differences
. 1. 3. 1
| Immunoassay Comparison | ||
|---|---|---|
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott ArchitectHE4 (K093957) |
| General Assay Features | ||
| IntendedUse/Indicationsfor Use | The Elecsys HE4 assay is animmunoassay for the quantitativedetermination of HE4 in human serumand plasma. The assay is used as an aidin monitoring the recurrence orprogressive disease in patients withepithelial ovarian cancer. Serial testingfor patient HE4 assay values should beused in conjunction with other clinicalfindings used for monitoring ovariancancer.The electrochemiluminescenceimmunoassay "ECLIA" is intended foruse on Elecsys and cobas e immunoassayanalyzers. | The ARCHITECT HE4 assay is achemiluminescent microparticleimmunoassay (CMIA) for the quantitativedetermination of the HE4 antigen inhuman serum.The assay is to be used as an aid inmonitoring recurrence or progressivedisease in patients with epithelial ovariancancer. Serial testing for patient HE4assay values should be used inconjunction with other clinical methodsused for monitoring epithelial ovariancancer. |
| AssayProtocol | Quantitative sandwich immunoassay | Quantitative chemiluminescentmicroparticle immunometric assay |
| DetectionProtocol | 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 | ||
| InstrumentPlatform | Elecsys 2010 and MODULARANALYTICS E170; Cobas e 411, cobas e601 and cobas e 602 | ARCHITECT i 2000, i 2000SR, i 1000 and i1000SR. |
| SampleVolume | 10 μL | 75 μL for first test plus 25 μL for eachadditional test from the same sample cup.≤ 3 hours on board: 150 μL for the firsttest plus 25 μL for each additional testfrom the same sample cup. |
| SampleType | Human serum and plasma treated withK2-EDTA, K3-EDTA or lithium heparin. | Human serum |
| Reagents | The Elecsys HE4 assay is a sandwichimmunoassay which includes abiotinylated monoclonal, murine HE4-specific IgG antibody as capture and aruthenium labeled monoclonal, murineHE4-specific IgG antibody as signal. | The Abbott ARCHITECT HE4 is a two-step immunoassay for the quantitativedetermination of HE4 antigen in humanserum using CMIA technology withflexible assay protocols, referred to asChemiflex. |
| Calibrator | Elecsys HE4 CalSet, 2 levels | Abbott ARCHITECT HE4 Calibrators, 6levels |
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Comparison of Assays—Similarities and Differences, continued
| Feature | Elecsys HE4 Assay | Predicate Devices: Abbott Architect HE4 (K093957) |
|---|---|---|
| General Assay Features | ||
| CalibrationInterval | Calibration must be performed once perreagent lot using fresh reagent (i.e. notmore than 24 hours since the reagent kitwas registered on the analyzer).Renewed calibration is recommended asfollows:After 28 days when using thesame reagent lot. After 7 days (when using thesame reagent kit on theanalyzer). As required: e.g. quality controlfindings outside the specifiedlimits | Once an ARCHITECT HE4 calibration isaccepted and stored, all subsequentsamples may be tested without furthercalibration unless one or more of thefollowing occur:A reagent kit with a new lotnumber 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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Comparison of Assays—Similarities and Differences, continued
、
| 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 dateAfter opening at 2-8 °C—12 weeksOn 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.When stored and handled as directed, the reagents are stable until the expiration date.The ARCHITECT HE4 Reagent Kit may be stored on board the ARCHITECT i System for a maximum of 30 days.Reagents may be stored on or off the ARCHITECT 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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Comparison of Assays-Similarities and Differences, continued
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott ArchitectHE4 (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)n=84 | Within-runn=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 | ||||||||
| AnalyticalSensitivity | On the e411:Limit of Blank (LoB) 5.0 pmol/LLimit of Detection (LoD) 15.0 pmol/LLimit of Quantitation (LoQ) 20.0 pmol/Lwith a total allowable error of 30% | Limit of Blank: 0.1 pmol/LLimit of Detection: ≤ 15 pmol/LFunctional Sensitivity: 20 pmol/L | ||||||
| AnalyticalSpecificity | Proteins (WFDC family) Reactivity Elafin/ SKALPat 54,500 pmol/L 0.025% SLPI at 20,833pmol/L 0.088 | No cross reactivity of above +/- LoD (<15 pmol/L) was seen with the following interferents tested:• CA 125• CA 15-3• CA 19-9• CEA• 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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100 - 100
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Comparison of Assays—Similarities and Differences, continued
| 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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Comparison of Assays—Similarities and Differences, continued
| 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 = 131Min = 17.0 pmol/LMax = 1405.0 pmol/L | Passing/Bablok Linear Regression Slope1.01(1.00-1.02) 1.00(0.994-1.01) Intercept-0.435(-1.03-0.365) 2.29(1.01-3.56) Tau/r0.979 0.999 |
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Clinical Sensitivity and Specificity Elecsys HE4
| PercentChangein HE4 | Sensitivity(%)(n/N) | Lower CI(95%) forSensitivity | Upper CI(95%) forSensitivity | Specificity (%)(n/N) | Lower CI(95%) forSpecificity | Upper CI(95%) forSpecificity |
|---|---|---|---|---|---|---|
| 0 | 69.14 (56/81) | 57.61 | 80.88 | 57.83(192/332) | 52.35 | 63.44 |
| 5 | 62.96 (51/81) | 50.63 | 75.61 | 68.07(226/332) | 62.71 | 73.08 |
| 10 . | 54.32 (44/81) | 42.13 | 66.67 | 74.70(248/332) | 69.47 | 79.32 |
| 14 | 50.62 (41/81) | 39.34 | 62.09 | 77.41(257/332) | 72.52 | 81.76 |
| 15 | 49.38 (40/81) | 38.28 | 60.48 | 78.31(260/332) | 73.68 | 82.51 |
| 20 | 46.91 (38/81) | 35.44 | 58.44 | 84.04(279/332) | 80.12 | 87.76 |
| 25 | 39.51 (32/81) | 28.84 | 51.23 | 87.05(289/332) | 83.56 | 90.34 |
| 50 | 24.69 (20/81) | 16.00 | 34.52 | 95.78(318/332) | 93.65 | 97.64 |
| 75 | 17.28 (14/81) | 9.20 | 26.75 | 97.59(324/332) | 95.92 | 99.02 |
| 100 | 14.81 (12/81) | 7.50 | 23.94 | 97.89(325/332) | 96.29 | 99.19 |
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| PercentChange inHE4 | Sensitivity(%) | Specificity(%) | 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:• Store at 2 - 8°C up to the stated expiration date.After reconstitution:• At 2 - 8°C: 7 days.• At -20°C: 8 weeks (freeze only once).• On Elecsys 2010/cobas e 411 at 20 - 25°C: Up to 5 hours.• On MODULAR ANALYTICS E170/cobas e 601 and 602: Use only once. | Unopened:• Store at 2 - 8°C up to the stated expiration date.After reconstitution:• At 2 - 8°C: 7 days• At -20°C: 28 days (freeze only once).• On Elecsys 2010/cobas e 411 at 20 - 25°C: Up to 5 hours.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:Elecsys PreciControlMultimarker (K102157) |
| Intended Use | Elecsys PreciControl HE4 is used forquality control of Elecsys HE4 on theElecsys and cobas e immunoassayanalyzers. | Elecsys PreciControl Multimarker isused for quality control of specifiedElecsys immunoassays on the Elecsysand cobas e immunoassay analyzers. |
| Levels | Two | Same |
| Format | Lyophilized | Same |
| Matrix | Human serum | Same |
| AnalyteConcentration | Approximately 50 and 400 pmol/L | C-Peptide (synthetic): Approximately2 and 10 ng/mL.Insulin (human recombinant fromyeast): Approximately 25 and 80μU/mL.ACTH (synthetic): Approximately 50and 1,000 pg/mL.hGH (human recombinant from E.coli): Approximately 1 and 10 ng/mL. |
| Stability | Unopened:• Store at 2-8°C up to the statedexpiration date.Reconstituted:• 2 - 8°C: 14 days• -20°C: 4 weeks (freeze only once)• On the analyzers at 20-25°C: up to 5hoursAt 20-25°C: 24 hours | Unopened:• Store at 2-8°C up to the statedexpiration date.Reconstituted:• 2 - 8°C: 72 hours• -20°C: 31 days (freeze only once)• On the analyzers at 20-25°C: up to5 hours |
| Handling | Carefully dissolve the contents of onebottle by adding exactly 1.0 mL ofdistilled or deionized water and allow tostand closed for 15 minutes toreconstitute. Mix carefully, avoiding theformation of foam. Transfer thereconstituted control into the empty,labeled snap-cap bottles supplied orfreeze aliquots in additional snap-capbottles (ControlSet Vials). Attach thesupplied labels to these bottles. Performonly one control procedure per aliquot. | Dissolve carefully the contents of onebottle by adding exactly 2.0 mL ofdistilled or deionized water and allowto stand closed for 30 minutes toreconstitute. Mix carefully, avoidingthe formation of foam. Transfer thereconstituted control into empty,labeled snap-cap bottles supplied(ControlSet Vials) and freeze aliquotsimmediately in additional ControlSetVials. Attach the supplied labels tothese additional bottles. Perform onlyone control procedure per aliquot. |
| Characteristic | Elecsys HE4 CalCheck 5 | Predicate Device:Elecsys DHEA-S CalCheck 5(K103402) |
| Intended Use | The Elecsys HE4 CalCheck 5 is anassayed control for use in calibrationverification and for use in the verificationof the assay range established by theElecsys HE4 reagent on the indicatedElecsys and cobas e immunoassayanalyzers. For In Vitro Diagnostic UseOnly. | The Elecsys DHEA-S CalCheck 5 is anassayed control for use in calibrationverification and for use in theverification of the assay rangeestablished by the Elecsys DHEA-Sreagent on the indicated Elecsys andcobas 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,Check 4 and Check 5 with exactly 1.0 mLdistilled or deionized water. Allow tostand closed for 15 minutes, then mixgently by inversion. | Same |
| Stability | Unopened:● Store at 2-8 °C up to the statedexpiration date.Reconstituted:● 20-25 °C: 5 hours | Unopened:● Store at 2-8 °C up to the statedexpiration date.Reconstituted:● 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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:
:
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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: (317) 521-3338
· FAX: (317) 521-2324
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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 (301) 796-5450. 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 (800) 638-2041 or (301) 796-7100 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
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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
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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
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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
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
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.(b)
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.