(368 days)
No
The summary describes a standard immunoassay for quantitative determination of a biomarker, with no mention of AI, ML, image processing, or any computational analysis beyond basic quantitative measurement and statistical evaluation of performance.
No
This device is an immunoassay intended for in vitro diagnostic use to aid in monitoring ovarian cancer. It provides diagnostic information and does not directly treat or alleviate a disease or condition.
Yes
The Elecsys HE4 assay is used as an aid in monitoring the recurrence or progressive disease in patients with epithelial ovarian cancer, which is a diagnostic purpose.
No
The device description explicitly states it is a sandwich immunoassay which includes physical components (antibodies) and is intended for use on immunoassay analyzers, indicating it is a hardware-based diagnostic test, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "quantitative determination of HE4 in human serum and plasma." This involves testing biological samples in vitro (outside the body).
- Assay Type: It describes an "immunoassay" and "electrochemiluminescence immunoassay (ECLIA)," which are common techniques used in IVD testing to measure substances in biological fluids.
- Purpose: The assay is used "as an aid in monitoring the recurrence or progressive disease in patients with epithelial ovarian cancer." This is a diagnostic purpose, providing information to help healthcare professionals manage a patient's condition.
- Device Description: The description of the assay components (antibodies, labels) is consistent with an IVD test kit.
- Performance Studies: The document includes details about performance evaluations like precision, linearity, method comparison, and clinical sensitivity and specificity, which are standard for demonstrating the analytical and clinical performance of an IVD.
- Predicate Device: The mention of a "Predicate Device" (K093957 Abbott Architect HE4) is a strong indicator that this device is being compared to an already cleared IVD.
All these elements point to the Elecsys HE4 assay being an In Vitro Diagnostic device.
N/A
Intended Use / 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 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.
Elecsys HE4 CalSet is used for calibrating the quantitative Elecsys HE4 assay on the Elecsys and cobas e immunoassay analyzers.
Elecsys PreciControl HE4 is used for quality control of the Elecsys HE4 immunoassay on Elecsys and cobas e immunoassay analyzers.
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.
Product codes (comma separated list FDA assigned to the subject device)
OIU, JIT, JJX
Device Description
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The Elecsys HE4 Immunoassay was evaluated for several characteristics. Evaluations including precision, limit of quantitation, linearity, method comparison, 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.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Sensitivity and Specificity Elecsys HE4
| Percent Change in HE4 | Sensitivity (%) (n/N) | Lower CI (95%) for Sensitivity | Upper CI (95%) for Sensitivity | Specificity (%) (n/N) | Lower CI (95%) for Specificity | Upper CI (95%) for Specificity |
|---|---|---|---|---|---|---|
| 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 |
Clinical Sensitivity and Specificity ARCHITECT HE4
| Percent Change in HE4 | 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 |
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Abbott Architect HE4 (K093957)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Elecsys hGH CalSet (K103221), Elecsys PreciControl Multimarker (K102157), Elecsys DHEA-S CalCheck 5 (K103402)
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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K112624
l
OCT 1 0 2012
Comparison of Assays—Similarities and Differences
. 1. 3. 1
| Immunoassay Comparison | ||
|---|---|---|
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect |
| HE4 (K093957) | ||
| General Assay Features | ||
| Intended | ||
| Use/ | ||
| 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 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 ARCHITECT HE4 assay is a
chemiluminescent microparticle
immunoassay (CMIA) for the quantitative
determination of the HE4 antigen in
human serum.
The assay is to be 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 methods
used for monitoring epithelial ovarian
cancer. |
| Assay
Protocol | Quantitative sandwich immunoassay | Quantitative chemiluminescent
microparticle immunometric assay |
| Detection
Protocol | Electrochemiluminescence | Chemiluminescence |
| Applications | 18 minute application | Not reported |
1
Continued
Comparison of Assays—Similarities and Differences, continued
| Immunoassay Comparison | ||
|---|---|---|
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect HE4 (K093957) |
| General Assay Features | ||
| Instrument | ||
| Platform | Elecsys 2010 and MODULAR | |
| ANALYTICS E170; Cobas e 411, cobas e | ||
| 601 and cobas e 602 | ARCHITECT i 2000, i 2000SR, i 1000 and i1000SR. | |
| Sample | ||
| Volume | 10 μL | 75 μL for first test plus 25 μL for each |
| additional test from the same sample cup. |
≤ 3 hours on board: 150 μL for the first
test plus 25 μL for each additional test
from the same sample cup. |
| Sample
Type | Human serum and plasma treated with
K2-EDTA, K3-EDTA or lithium heparin. | Human serum |
| Reagents | 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. | The Abbott ARCHITECT HE4 is a two-
step immunoassay for the quantitative
determination of HE4 antigen in human
serum using CMIA technology with
flexible assay protocols, referred to as
Chemiflex. |
| Calibrator | Elecsys HE4 CalSet, 2 levels | Abbott ARCHITECT HE4 Calibrators, 6
levels |
.
Continued on next page
・
·
2
Continued
3
Comparison of Assays—Similarities and Differences, continued
| Feature | Elecsys HE4 Assay | Predicate Devices: Abbott Architect HE4 (K093957) |
|---|---|---|
| General Assay Features | ||
| Calibration | ||
| Interval | Calibration must be performed once per | |
| reagent lot using fresh reagent (i.e. not | ||
| more than 24 hours since the reagent kit | ||
| was registered on the analyzer). | ||
| Renewed calibration is recommended as | ||
| follows: | ||
| After 28 days when using the | ||
| same reagent lot. After 7 days (when using the | ||
| same reagent kit on the | ||
| analyzer). As required: e.g. quality control | ||
| findings outside the specified | ||
| limits | Once an ARCHITECT HE4 calibration is | |
| accepted and stored, all subsequent | ||
| samples may be tested without further | ||
| calibration unless one or more of the | ||
| following occur: | ||
| A reagent kit with a new lot | ||
| number is used Controls are out of range | ||
| Controls | Elecsys HE4 PreciControl | Abbott ARCHITECT HE4 Controls |
Continued on next page .
3
and the comments of the comments of
4
Continued
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 date | |
| After opening at 2-8 °C—12 weeks | ||
| 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. |
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, |
4
Continued
5
Comparison of Assays-Similarities and Differences, continued
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect
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)
n=84 | Within-run
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 | |
5
.
Continued
Comparison of Assays—Similarities and Differences, continued
| Immunoassay Comparison | ||||||||
|---|---|---|---|---|---|---|---|---|
| Feature | Elecsys HE4 Assay | Predicate Device: Abbott Architect HE4 (K093957) | ||||||
| Labeled Performance Characteristics | ||||||||
| Analytical | ||||||||
| Sensitivity | On the e411: | |||||||
| 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% | Limit of Blank: 0.1 pmol/L | |||||||
| Limit of Detection: ≤ 15 pmol/L | ||||||||
| Functional Sensitivity: 20 pmol/L | ||||||||
| Analytical | ||||||||
| Specificity | Proteins (WFDC family) Reactivity Elafin/ SKALP | |||||||
| at 54,500 pmol/L 0.025% SLPI at 20,833 | ||||||||
| pmol/L 0.088 | No cross reactivity of above +/- LoD ( 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
14
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
15
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
16
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