ELECSYS CEA ASSAY

K964368 · Boehringer Mannheim Corp. · JIT · Jun 16, 1997 · Clinical Chemistry

Device Facts

• Record ID: K964368
• Device Name: ELECSYS CEA ASSAY
• Applicant: Boehringer Mannheim Corp.
• Product Code: JIT · Clinical Chemistry
• Decision Date: Jun 16, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1150
• Device Class: Class 2

Intended Use

Immunoassay for the in vitro quantitative determination of carcinoembryonic antigen (CEA) in human serum and plasma. Measurements of CEA aid in the management of cancer patients by monitoring CEA concentrations. The electrochemiluminescence immunoassay “ECLIA” is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.

Device Story

Elecsys CEA Assay is an in vitro diagnostic immunoassay for quantitative CEA measurement in human serum and plasma. Used on the Elecsys 2010 analyzer, the device employs an electrochemiluminescence (ECLIA) sandwich principle. Input: 30 μL sample, biotinylated monoclonal CEA-specific antibody, and ruthenium-labeled monoclonal CEA-specific antibody. These form a sandwich complex, which is captured on streptavidin-coated microparticles. Microparticles are magnetically captured on an electrode surface; unbound substances are removed via ProCell. Application of voltage induces chemiluminescent emission, measured by a photomultiplier. Results are calculated via a 2-point calibration curve and a master curve provided by reagent bar code. The assay aids clinicians in monitoring cancer patients through serial CEA concentration measurements. Benefits include improved management of cancer patients via quantitative monitoring.

Clinical Evidence

Bench testing only. Performance evaluated via precision (modified NCCLS), linearity (0.2–1000 ng/mL), and method comparison (N=397 and N=446) against the predicate. Sensitivity (lower detection limit 0.2 ng/mL) and specificity (cross-reactivity testing) were established. Clinical specimen testing included serial samples from 50 colorectal cancer patients, showing a statistically significant association between clinical outcome and CEA test results via Chi-square analysis.

Technological Characteristics

Electrochemiluminescence immunoassay (ECLIA). Uses streptavidin-coated microparticles and biotinylated antibodies. Instrumentation: Elecsys 2010 analyzer. Detection: Photomultiplier tube measuring chemiluminescent emission induced by electrode voltage. Calibration: 2-point calibration with master curve via reagent bar code. Sample types: Serum and plasma.

Indications for Use

Indicated for the in vitro quantitative determination of CEA in human serum and plasma to aid in the management of cancer patients by monitoring CEA concentrations.

Regulatory Classification

Identification

A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)

Special Controls

*Classification.* Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.

Predicate Devices

• Enzymun-Test CEA (P860058)

Submission Summary (Full Text)

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K964368
JUN 16 1997

# 510(k) Summary

| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
| --- | --- |
| 1. Submitter name, address, contact | Boehringer Mannheim Corporation
2400 Bisso Lane
P.O. Box 4117
Concord, CA 94524-4117
(510) 674 - 0690, extension 8415
Contact Person: Mary Koning
Date Prepared: October 31, 1996 |
| 2. Device name | Proprietary name: Elecsys® CEA Assay
Common name: Electrochemiluminescence assay for the determination of Carcinoembryonic antigen (CEA).
Classification name: Kit, Test, Carcinoembryonic antigen |
| 3. Predicate device | The Boehringer Mannheim Elecsys® CEA is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Enzymun-Test CEA (P860058). |
| 4. Device Description | The Elecsys® test principle is based on sandwich principle. Total duration of assay: 18 minutes (37° C).
• 1st incubation (9 minutes): Sample (30 μL), biotinylated monoclonal CEA-specific antibody (60 μL), 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 μL), the complex is bound to the solid phase via interaction of biotin and streptavidin. |

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# 510(k) Summary, Continued

4. Device Description, cont.

- 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.

5. Intended use

Immunoassay for the in vitro quantitative determination of carcinoembryonic antigen (CEA) in human serum and plasma.

Measurements of CEA aid in the management of cancer patients by monitoring CEA concentrations.

The electrochemiluminescence immunoassay “ECLIA” is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.

6. Comparison to predicate device

The Boehringer Mannheim Elecsys® CEA Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Enzymun-Test CEA Assay (P860058).

The following table compares the Elecsys® CEA Assay with the predicate device, Enzymun-Test CEA Assay (P860058):

## Similarities:

- Intended Use: Immunoassay for the in vitro quantitative determination of Carcinoembryonic Antigen (CEA). The assay is further indicated for serial measurement of CEA to aid in the management of cancer patients.
- Solid phase binding principle: Streptavidin/Biotin
- Calibrators: Same formulation
- Assay standardization: 1st WHO Reference Standard 73/601

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# 510(k) Summary, Continued

## 6. Comparison to predicate device, cont.

### Differences:

| Feature | Elecsys® CEA | Enzymun CEA |
| --- | --- | --- |
| Reaction test principle | Electrochemiluminescence | ELISA/1-step sandwich assay using streptavidin technology |
| Instrument required | Elecsys® 2010 | ES 300 |
| Antibodies | Mouse/chimeric | Mouse/mouse |
| Sample Material | Serum and Plasma | Serum |
| Calibration Stability | A calibration is recommended every 7 days if kit is not consumed; 8 weeks with same reagent lot if reagent is consumed within 7 days. | A calibration is required every run |

### Performance Characteristics:

| Feature | Elecsys® CEA | | | Enzymun-Test CEA | | |
| --- | --- | --- | --- | --- | --- | --- |
| Precision Level | Modified NCCLS (ng/mL): | | | Modified NCCLS (ng/mL): | | |
| | Control 1 | Control 2 | Pool 1 | Low | Mid | High |
| N | 60 | 60 | 60 | 120 | 120 | 120 |
| Within-Run | 5.10 | 35.51 | 3.99 | 2.3 | 12.4 | 26.4 |
| %CV | 1.8 | 1.4 | 1.7 | 5.6 | 3.7 | 3.3 |
| Total | 5.10 | 35.51 | 3.99 | 2.3 | 12.4 | 26.4 |
| %CV | 3.5 | 2.8 | 3.2 | 6.3 | 4.1 | 3.7 |
| | Modified NCCLS (ng/mL): | | | | | |
| | Pool 2 | Pool 3 | | | | |
| N | 60 | 60 | | | | |
| Within-Run | 17.16 | 546.00 | | | | |
| %CV | 1.7 | 1.4 | | | | |
| Total | 17.16 | 546.00 | | | | |
| %CV | 3.2 | 3.4 | | | | |

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# 510(k) Summary, Continued

## 6. Performance Characteristics:

Comparison to predicate device, cont.

| Feature | Elecsys® CEA | Enzymun-Test CEA |
| --- | --- | --- |
| Lower Detection Limit | 0.2 ng/mL | 0.5 ng/mL |
| Linearity | 0.2 - 1000 ng/mL (with a deviation from a linear line of ±10%) | 0.5 - 55 ng/mL (with a deviation from a linear line of ±10%) |
| Method Comparison | Vs Enzymun-Test® CEA
0 - 50 ng/mL
Least Squares
y = 1.25x - 0.86
r = 0.976
SEE = 1.421
N = 397

Passing/Bablok
y = 1.22x - 0.69
r = 0.976
SEE = 0.471
N = 397

0 - 600 ng/mL
Least Squares
y = 1.05x + 0.46
r = 0.991
SEE = 6.093
N = 446

Passing/Bablok
y = 1.13x - 0.53
r = 0.991
SEE = 0.714
N = 446 | Vs Enzymun-Test® CEA
Least Squares
y = 0.97x - 0.064
r = 0.989
SEE = 1.649
N = 69 |

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# 510(k) Summary, Continued

## 6. Comparison to predicate device, cont.

### Performance Characteristics:

| Feature | Elecsys® CEA | Enzymun-Test CEA |
| --- | --- | --- |
| Interfering substances | No interference at: | No interference at: |
| Bilirubin | 25 mg/dL | 64.5 mg/dL |
| Hemoglobin | 1000 mg/dL | 50 mg/dL |
| Lipemia | 1000 mg/dL | 1250 mg/dL |
| Biotin | 30 ng/mL | 40 ng/mL |
| Specificity | % Cross-reactivity | % Cross-reactivity |
| Non-specific cross reacting antigen | | |
| NCA 1 | < 0.7% | < 0.7% |
| NCA 2 | 70% | 70% |
| α_{1}-acid glycoprotein | none | none |
| Hook Effect | No Hook Effect up to 49,100 ng/ml CEA | No Hook Effect up to 5,800 ng/ml CEA |

## 6. Comparison to predicate device, cont.

### Clinical specimens

Serial samples from 50 patients with colorectal cancer were tested on the Elecsys CEA. Chi square analysis of the samples showed a statistically significant association between clinical outcome and CEA test result.

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DEPARTMENT OF HEALTH &amp; HUMAN SERVICES
Public Health Service
JUN 16 1997
Food and Drug Administration
2098 Gaither Road
Rockville MD 20850

Ms. Mary Koning
Regulatory Affairs Specialist
Boehringer Mannheim Corporation
2400 Bisso Lane
Concord, California 94524-4117

Re: K964368/S1
Trade Name: Elecsys® CEA Assay and Elecsys® CEA CalSet Calibrators Regulatory Class: II
* Product Code: DHX
Dated: April 30, 1997
Received: May 1, 1997

Dear Ms. Koning:

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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory 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 Regulations.

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 [phone].

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Page 2

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 labeling regulation (21 CFR Part 801 and additionally 809.10 for *in vitro* diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. 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 [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

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