(112 days)
Immunoassay for the in vitro quantitative determination of carcinoembryonic antigen (CEA) in human serum and plasma. The Elecsys CEA assay if further indicated for serial measurement of CEA to aid in the management of cancer patients.
The electrochemiluminescence immunoassay “ECLIA” is intended for use on the Boehringer Mannheim Elecsys 1010 and 2010 immunoassay analyzers.
The Elecsys® test principle is based on sandwich principle. Total duration of assay: 18 minutes (37°C).
· 1st incubation (9 minutes): Sample (30 uL), biotinylated monoclonal CEA-specific antibody (60 uL), and a monoclonal CEA-specific antibody labeled with a ruthenium complex (60 µL) react to form a sandwich complex.
·2nd incubation (9 minutes): After addition of streptavidin-coated microparticles (50 uL), the complex is bound to the solid phase via interaction of biotin and streptavidin.
•The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame).
•Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code.
Here's an analysis of the provided text, focusing on acceptance criteria and supporting study details:
The document describes the Elecsys® CEA Assay for use on the Elecsys® 1010 immunoassay analyzer, asserting its substantial equivalence to the same assay on the Elecsys® 2010. The study presented here is a comparison study between two devices rather than a standalone study for a single device, so many of the requested categories are not directly applicable.
Description of Acceptance Criteria and Supporting Study
The acceptance criteria for the Elecsys® CEA Assay on the Elecsys® 1010 are implicitly defined by its performance characteristics being substantially equivalent to the predicate device, the Elecsys® CEA Assay on the Elecsys® 2010. The study detailed below compares these performance characteristics.
1. Table of Acceptance Criteria and Reported Device Performance
Since this is a substantial equivalence claim for a new instrument (Elecsys® 1010) using an already cleared assay (Elecsys® CEA Assay on Elecsys® 2010), the "acceptance criteria" are the performance specifications of the predicate device. The reported device performance is for the Elecsys® CEA Assay on the Elecsys® 1010.
| Feature | Acceptance Criteria (Predicate: Elecsys® 2010) | Reported Device Performance (Elecsys® 1010) |
|---|---|---|
| Precision | Modified NCCLS (ng/mL): | Modified NCCLS (ng/mL): |
| Control 1 | N=60 | N=60 |
| Within-Run | 4.9 ng/mL / 2.5 %CV | 4.44 ng/mL / 2.36 %CV |
| Total | 4.9 ng/mL / 3.6 %CV | 4.44 ng/mL / 3.07 %CV |
| Control 2 | N=60 | N=60 |
| Within-Run | 34.1 ng/mL / 1.7 %CV | 32.96 ng/mL / 1.71 %CV |
| Total | 34.1 ng/mL / 3.0 %CV | 35.51 ng/mL / 2.09 %CV |
| Pool 1 | N=60 | Not reported for Elecsys® 1010 |
| Within-Run | 2.2 ng/mL / 5.0 %CV | |
| Total | 2.2 ng/mL / 5.4 %CV | |
| Pool 2 | N=60 | N=60 |
| Within-Run | 19.6 ng/mL / 1.6 %CV | 11.86 ng/mL / 1.57 %CV |
| Total | 19.6 ng/mL / 2.3 %CV | 11.86 ng/mL / 2.83 %CV |
| Pool 3 | N=60 | N=60 |
| Within-Run | 528 ng/mL / 1.3 %CV | 113.64 ng/mL / 2.89 %CV |
| Total | 528 ng/mL / 2.0 %CV | 113.64 ng/mL / 3.97 %CV |
| Lower Detection Limit | 0.2 ng/mL | 0.2 ng/mL |
| Linearity | 0.2 - 1000 ng/mL (±10% deviation) | 0.2 - 1000 ng/mL (±10% deviation) |
| Method Comparison | (Predicate Elecsys® 2010 data) | Vs Elecsys® 2010: |
| Least Squares | y = 1.006x - 0.64; r = 0.995; N = 117 | |
| Passing/Bablok | y = 0.958x + 0.14; r = 0.995; N = 117 | |
| Hook Effect | No Hook Effect up to 200,000 ng/mL CEA | No Hook Effect up to 200,000 ng/mL CEA |
Note: The table shows that the Elecsys® 1010 assay results are generally comparable to or better than the Elecsys® 2010 for precision, except for Pools 2 and 3 where the absolute CEA values tested are different between the two instruments in the provided summary (11.86 vs 19.6 for Pool 2, and 113.64 vs 528 for Pool 3). However, the %CV values (indicating precision) remain in a similar range. For other features like lower detection limit, linearity, and hook effect, the results are identical. The method comparison directly demonstrates equivalence to the predicate.
2. Sample Size Used for the Test Set and Data Provenance
- Precision Test Set Sample Size (N):
- For the Elecsys® 1010 and Elecsys® 2010, the precision studies used N=60 for each control/pool level (Controls 1 & 2, Pools 1, 2 & 3). This "N" represents the number of replicate measurements performed on each control/pool over the testing period.
- Method Comparison Test Set Sample Size:
- N = 117 samples were used for the method comparison study between the Elecsys® 1010 and Elecsys® 2010.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). Given the nature of a 510(k) submission for an in vitro diagnostic, it is highly probable these were controlled prospective studies conducted in a laboratory setting by the manufacturer to validate the device's performance.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable for this type of in vitro diagnostic device study. The "ground truth" for an immunoassay largely relies on the accuracy of calibrators and controls traced to established reference materials, as opposed to expert human interpretation. The output is a quantitative measurement of CEA in a sample.
4. Adjudication Method for the Test Set
Not applicable. As described above, this is a quantitative measurement device, not an interpretation-based device requiring adjudication of human readings.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
Not applicable. This is an in vitro diagnostic immunoassay without human interpretation as a primary component. It is an automated quantitative measurement system; there are no "human readers" in the context of interpretation.
6. If a Standalone (i.e. Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, this is essentially a standalone (algorithm only) performance study. The device (Elecsys® CEA Assay on Elecsys® 1010) provides quantitative results without requiring human interpretation that influences the numerical outcome. The study directly evaluates the analytical performance characteristics of the physical device and its associated reagents.
7. The Type of Ground Truth Used
The ground truth for an immunoassay is established through a combination of:
- Reference Materials and Calibrators: The device's calibration curve is generated using calibrators with known concentrations, traceable to international or recognized reference materials for CEA.
- Control Materials: Quality control materials with established target values are run to monitor assay performance.
- Reference Method (for Method Comparison): In the method comparison study, the Elecsys® 2010, the legally marketed predicate device, served as the comparative "ground truth" or reference method against which the Elecsys® 1010 was evaluated.
The ultimate ground truth for a diagnostic test like CEA is based on clinical outcomes (e.g., cancer diagnosis or recurrence), but the studies presented here are analytical performance studies.
8. The Sample Size for the Training Set
Not explicitly stated. For in vitro diagnostic devices, especially immunoassay platforms, the term "training set" is usually not used in the same context as machine learning. Instead, the instrument and assay are developed and optimized through extensive R&D and internal validation using numerous samples (often a much larger set than the formal validation studies) to establish robust calibration algorithms and performance characteristics. The document presents the final validation data.
9. How the Ground Truth for the Training Set Was Established
Not explicitly stated. During the development and optimization (analogous to "training") of an immunoassay, the "ground truth" for samples used would be established using validated reference methods, internal gold standard assays, and reference materials with assigned values, often in conjunction with clinical samples that have confirmed diagnoses or outcomes. This iterative process allows for the refinement of reagents, instrument parameters, and algorithms to achieve desired performance.
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JUN 2 9 1998
:
KC980887
510(k) Summary
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. |
|---|---|
| 1.Submittername, address,contact | Boehringer Mannheim Corporation4300 Hacienda DriveP.O. Box 9002Pleasanton, CA 94566-0900(510) 730-8215Contact Person: Patricia M. KlimleyDate Prepared: March 6, 1998 |
| 2.Device name | Proprietary name: Elecsys® CEA AssayCommon name: Electrochemiluminescence assay for the determination ofCarcinoembryonic antigen (CEA).Classification name: Kit, Test , Carcinoembryonic antigen |
| 3.Predicate device | The Boehringer Mannheim Elecsys® CEA on Elecsys® 1010 is substantiallyequivalent to other products in commercial distribution intended for similaruse. Most notably it is substantially equivalent to the currently marketedElecsys® CEA on Elecsys® 2010. |
| 4.DeviceDescription | The Elecsys® test principle is based on sandwich principle. Total duration ofassay: 18 minutes (37°C).· 1st incubation (9 minutes): Sample (30 uL), biotinylated monoclonal CEA-specific antibody (60 uL), and a monoclonal CEA-specific antibody labeledwith a ruthenium complex (60 µL) react to form a sandwich complex.·2nd incubation (9 minutes): After addition of streptavidin-coatedmicroparticles (50 uL), the complex is bound to the solid phase via interactionof biotin and streptavidin. |
| 4.DeviceDescription(con't) | •The reaction mixture is aspirated into the measuring cell where themicroparticles are magnetically captured onto the surface of the electrode.Unbound substances are then removed with ProCell. Application of a voltageto the electrode then induces chemiluminescent emission which is measured bya photomultiplier (0.4 second read frame).•Results are determined via a calibration curve which is instrument-specificallygenerated by 2-point calibration and a master curve provided via the reagentbar code. |
| 5.Intended use | Immunoassay for the in vitro quantitative determination of carcinoembryonicantigen (CEA) in human serum and plasma. The Elecsys CEA assay if furtherindicated for serial measurement of CEA to aid in the management of cancerpatients.The electrochemiluminescence immunoassay “ECLIA” is intended for use onthe Boehringer Mannheim Elecsys 1010 and 2010 immunoassay analyzers.Summary |
Continued on next page
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510(k) Summary, Continued
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6. Comparison to predicate device
The Boehringer Mannheim Elecsys® CEA Assay has been approved for use on the Elecsys 2010 immunoassay analyzer (K964368). The application of the Elecsys® CEA Assay on the Elecsys 1010 immunoassay analyzer is substantially equivalent to the same assay (Elecsys CEA Assay) on the Elecsys 2010.
The following table compares the Elecsys® CEA Assay on Elecsys® 1010 with the predicate device, Elecsys® CEA Assay on Elecsys® 2010 . Specific data on the performance of this test for both the Elecsys 1010 and 2010 have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device in attachment 6 will be replaced upon the clearance of this premarket notification submission with the combined Elecsys 2010 and 1010 insert (attachment 5).
Similarities:
•Intended Use: Immunoassay for the in vitro quantitative determination of Carcinoembryonic Antigen (CEA). The assay is further indicated for the serial measurement of CEA to aid in the management of cancer patients.
- ·Assay range: 0-1000 ng/mL
- · Assay methodology: Sandwich immunoassay
- ·Kit (cat. No.) also cleared for use on the Elecsys 2010 (K964368 )
·Sample and reagent volumes
·Package insert
- ·Performance specifications
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510(k) Summary, Continued
Differences:
Comparison to predicate device cont.
| Feature | Elecsys® 1010 | Elecsys® 2010 |
|---|---|---|
| Instrumentrequired | Elecsys 1010 | Elecsys 2010 |
| InstrumentType | Batch | Random access |
| ReagentStorage Temp(C) | Ambient Temperature | 20° C |
Performance Characteristics:
| Feature | Elecsys® 1010 | Elecsys® 2010 | |||
|---|---|---|---|---|---|
| Precision | Modified NCCLS (ng/mL): | Modified NCCLS (ng/mL): | |||
| Level | Control 1 | Control 2 | Control 1 | Control 2 | Pool 1 |
| N | 60 | 60 | 60 | 60 | 60 |
| Within-Run | 4.44 | 32.96 | 4.9 | 34.1 | 2.2 |
| %CV | 2.36 | 1.71 | 2.5 | 1.7 | 5.0 |
| Total | 4.44 | 35.51 | 4.9 | 34.1 | 2.2 |
| %CV | 3.07 | 2.09 | 3.6 | 3.0 | 5.4 |
| Modified NCCLS (ng/mL): | Modified NCCLS (ng/mL): | ||||
| Pool 2 | Pool 3 | Pool 2 | Pool 3 | ||
| N | 60 | 60 | 60 | 60 | |
| Within-Run | 11.86 | 113.64 | 19.6 | 528 | |
| %CV | 1.57 | 2.89 | 1.6 | 1.3 | |
| Total | 11.86 | 113.64 | 19.6 | 528 | |
| %CV | 2.83 | 3.97 | 2.3 | 2.0 |
Continued on next page
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510(k) Summary, Continued
- September 2017
| Performance Characteristics: | ||
|---|---|---|
| Feature | Elecsys® 1010 | Elecsys® 2010 |
| LowerDetection Limit | 0.2 ng/mL | 0.2 ng/mL |
| Linearity | 0.2 - 1000 ng/mL (with adeviation from a linear line of±10%) | 0.2 - 1000 ng/mL (with adeviation from a linear line of±10%) |
| MethodComparison | Vs Elecsys 2010Least Squares$y=1.006x - 0.64$$r=0.995$$N=117$Passing/Bablok$y=0.958x + 0.14$$r=0.995$$N=117$ | |
| Hook Effect | No Hook Effect up to200,000 ng/mL CEA | No Hook Effect up to200,000 ng/mL CEA |
Performance Characteristics:
:
!
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Image /page/5/Picture/2 description: The image is a black and white seal for the Department of Health and Human Services - USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is a stylized image of an eagle.
JUN 2 9 1998
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Patricia M. Klimley Manager, Regulatory Affairs Boehringer Mannheim Corporation 4300 Hacienda Drive P.O. Box 9002 Pleasanton, California 94566-0900
Re : K980887 / S1 Trade Name: Elecsys® CEA Assay Requlatory Class: II Product Code: DHX Dated: May 4, 1998 Received: May 5, 1998
Dear Ms. Klimley:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in requlatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Requlations.
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Paqe 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
This letter will allow you to begin marketing your device as described in your 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 labelinq regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) Additionally, for questions on the promotion and 594-4588. advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Butman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number (if known): K980887
Device Name: Elecsys® CEA Assay
Intended use
Intended use
Immunoassay for the in vitro quantitative determination of carcinoembryonic antigen in
the serial Immunoassay for the in vitro qualificant and is further indicated for serial
human serum and plasma. The Elecsys assement of capcer natients. measurement of CEA to aid in the management of cancer patients. The electrochemiluminescence immunoassay "ECLA" is intended for use on the
The electrochemiluminescence immunoassay "ECLA" is intended for use on the The electrochemiummescence Inindhoussay - 2 commentsay analyzers.
Boehringer Mannheim Elecsys 1010 and 2010 immunoassay analyzers.
Peter. Mapes
(Division Sign ()ft) 298868 Division and Division ! 510(x) Number -
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________
(Optional Format 1-2-96)
§ 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.