ELECSYS CA 19-9 IMMUNOASSAY, ELECSYS CA 19-9 CALSET

K050231 · Roche Diagnostics Corp. · JIT · Jul 6, 2005 · Clinical Chemistry

Device Facts

• Record ID: K050231
• Device Name: ELECSYS CA 19-9 IMMUNOASSAY, ELECSYS CA 19-9 CALSET
• Applicant: Roche Diagnostics Corp.
• Product Code: JIT · Clinical Chemistry
• Decision Date: Jul 6, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1150
• Device Class: Class 2

Intended Use

The Elecsys CA 19-9 Immunoassay is an immunoassay for the in vitro quantitative determination of CA 19-9 tumor associated antigen in human serum and plasma. The assay is indicated for the serial measurement of CA 19-9 to aid in the management of patients diagnosed with cancers of the exocrine pancreas. The test is useful as an aid in the monitoring of disease status in those patients having confirmed pancreatic cancer who have levels of CA 19-9 at some point in their disease process exceeding the median concentration determined for the apparently healthy cohort. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010/2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay analyzers. The Elecsys CA 19-9 CalSet is used for calibrating the quantitative Elecsys CA 19-9 assay on the Elecsys immunoassay systems.

Device Story

Two-step sandwich immunoassay using streptavidin-coated microparticles and electrochemiluminescence (ECLIA) detection; measures CA 19-9 tumor-associated antigen in human serum/plasma. Operated by laboratory personnel on Roche Elecsys 1010/2010 or MODULAR ANALYTICS E170 systems. Input: patient serum/plasma sample; process: automated binding and signal generation; output: quantitative CA 19-9 concentration (U/mL) derived from instrument-specific calibration curve and master reagent curve. Used for serial monitoring of disease status in confirmed pancreatic cancer patients. Results assist clinicians in tracking disease progression/response to therapy. Benefits: provides quantitative data for longitudinal patient management.

Clinical Evidence

Prospective study of 89 pancreatic cancer patients (363 samples). Evaluated serial monitoring concordance between test and predicate devices. Positive concordance 0.621 (95% CI: 0.493, 0.733) and negative concordance 0.652 (95% CI: 0.588, 0.711) for test device. Total concordance 0.642. Per-patient positive concordance 0.872 (95% CI: 0.768, 0.938).

Technological Characteristics

Two-step sandwich immunoassay; electrochemiluminescence detection; streptavidin-coated microparticles; ruthenium-labeled antibodies. Analyzers: Elecsys 1010/2010, MODULAR ANALYTICS E170. Measuring range: 0.60-1000 U/mL. Calibration: 2-point calibration against master curve provided via reagent bar code.

Indications for Use

Indicated for serial measurement of CA 19-9 to aid in management of patients with confirmed exocrine pancreatic cancer who have baseline CA 19-9 levels exceeding the median concentration of an apparently healthy cohort. Contraindicated in patients genotypically negative for Lewis blood group antigen, as they cannot produce CA 19-9.

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

• Fujirebio Diagnostics CA 19-9™ RIA (k020566)

Submission Summary (Full Text)

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K05023/

Elecsys® CA 19-9 Test System

JUL 6 - 2005

Roche Diagnostics

## 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. | |
|----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------|
| Submitter name, address, contact | Roche Diagnostics<br>9115 Hague Road<br>Indianapolis, IN 46250<br>[phone]<br>Contact Person: Kay A. Taylor | |
| Device Name | Proprietary name: | Elecsys CA 19-9 Immunoassay<br>Elecsys CA 19-9 CalSet |
| | Common name: | Immunological test for CA 19-9 antigen<br>Calibrator |
| | Classification name: | System, Test, Carbohydrate Antigen (CA 19-9), for monitoring and management of Pancreatic Cancer<br>Calibrator, secondary |
| Device Description | The Elecsys CA 19-9 Assay is a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve provided with the reagent bar code. | |

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Elecsys® CA 19-9 Test System

### 510(k) Summary, Continued

Immunoassay for the in vitro quantitative determination of CA 19-9 tumor Intended use associated antigen, in human serum and plasma. The assay is indicated for the serial measurement of CA 19-9 to aid in the management of patients diagnosed with cancers of the exocrine pancreas. The test is useful as an aid in the monitoring of disease status in those patients having confirmed pancreatic cancer who have levels of CA 19-9 at some point in their disease process exceeding the median concentration determined for the apparently healthy cohort. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010/2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay systems.

> Elecsys CA 19-9 CalSet is used for calibrating the quantitative Elecsys CA 19-9 assay on the Elecsys immunoassay systems.

The Elecsys CA 19-9 immunoassay test system is substantially equivalent to Substantial other devices legally marketed in the United States. We claim equivalence to equivalence the Fujirebio Diagnostics CA 19-9 RIA cleared under K020566. Both products are intended for use in the quantitative determination of CA 19-9 tumor associated antigen in human serum and plasma.

| Substantial<br>equivalence -<br>comparison | The following table compares the Roche Elecsys CA 19-9 Immunoassay with<br>the predicate device. |
|--------------------------------------------|--------------------------------------------------------------------------------------------------|
|--------------------------------------------|--------------------------------------------------------------------------------------------------|

| Feature | Elecsys CA 19-9 | Fujirebio CA 19-9 RIA<br>(predicate) |
|--------------------|--------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------|
| Intended Use | In vitro quantitative<br>determination of CA 19-9 tumor-<br>associated antigen in serum and<br>plasma. | In vitro quantitative<br>determination of CA 19-9<br>tumor-associated antigen in<br>serum and plasma. |
| Indication for Use | An aid in the management of<br>patients with cancers of the<br>exocrine pancreas. | An aid in the management of<br>patients with cancers of the<br>exocrine pancreas. |
| Assay Principle | Electrochemiluminescent<br>immunoassay | Radioimmunoassay |
| Sample Type | Human serum and plasma | Human serum and plasma |

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| Feature | Elecsys CA 19-9 | Fujirebio CA 19-9 RIA<br>(predicate) |
|-----------------|--------------------------------------------------|-------------------------------------------------------------------------------------------|
| Calibrator | Elecsys CA 19-9 CalSet (2<br>levels) | CA 19-9 Standard set (6 levels<br>including 0) |
| Controls | PreciControl Tumor Marker (2<br>level) | Defibrinated human plasma<br>containing 2 levels of Ca 19-9 |
| Instrument | Elecsys 1010, 2010 and<br>MODULAR ANALYTICS E170 | Manual method or semi-automated with commercially<br>available rinsing/aspiration systems |
| Measuring range | 0.60 - 1000 U/mL | 0.9 - 240 U/mL |

### 510(k) Summary, Continued

The performance characteristics of the Elecsys CA 19-9 Immunoassay and Substantial equivalence the predicate device are compared in the table below. performance characteristics

| Feature | Elecsys CA 19-9 | Fujirebio CA 19-9 RIA<br>(predicate) |
|---------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------|
| Precision | 1010/2010<br>Within-run<br>2.9%-4.8% CV @ 11.1-185.4 U/mL<br>Total Precision<br>2.9%-4.4% CV @ 11.1-185.4 U/mL<br><br>E170<br>Within-run<br>1.2%-2.5% CV @ 5.2-379 U/mL<br>Total Precision<br>1.9%-8.0% CV @ 5.57-371 U/mL | Average variability ranged from<br>6.7% (44 U/mL) to 15.4% (8 U/mL). |
| Analytical<br>sensitivity (LDL) | 0.60 U/mL | 0.9 U/mL |
| Hook Effect | No high dose hook effect up to<br>500,000 U/mL | None up to 1,250,000 U/mL |

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# 510(k) Summary, Continued

| Feature | Elecsys CA 19-9 | Fujirebio CA 19-9 RIA<br>(predicate) |
|-------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Limitations | The assay is unaffected by icterus (bilirubin < 1129 µmol/L or < 66 mg/dL), hemolysis (Hb < 1.4 mmol/L or < 2.2 g/dL), lipemia (Intralipid < 1500 mg/dL), and biotin < 100 ng/mL. In patients receiving therapy with high biotin doses (i.e. > 5 mg/day), no sample should be taken until at least 8 hours after the last biotin administration. No interference was observed from rheumatoid factors up to a concentration of 1500 IU/mL. In vitro tests were performed on 27 commonly used pharmaceuticals. No interference with the assay was found. As with all tests containing monoclonal mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or have received them for diagnostic purposes. Elecsys CA 19-9 contains additives which minimize these effects. In rare cases, interference due to extremely high titers of antibodies to streptavidin and ruthenium can occur. | This assay should not be performed on clotted, icteric, hemolyzed or lipemic samples. Human anti-mouse antibodies (HAMA) may be present in samples from patients who have received mouse monoclonal antibodies for immunotherapy. Such sample may show false elevated or depressed values when tested with this method. Results for patients suspected of having such antibodies should be carefully evaluated and interpreted in the context of the clinical status of the patient. Can be used with serum and plasma prepared using different anti-coagulants (ACD-A, Citrate, EDTA, and Heparin). However, it is recommended that if the specimen type is changed during patient monitoring, the patient should be rebaselined to negate any potential biases due to specimen type. Patients known to be genotypically negative for the Lewis blood group antigen will be unable to produce the CA 19-9 antigen even in the presence of malignant tissue. Phenotyping for the presence of the Lewis antigen may be produce varying levels of CA 19-9 based on gene dosage effect. |

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# 510(k) Summary, Continued

| Feature | Elecsys CA 19-9 | Fujirebio CA 19-9 RIA<br>(predicate) |
|-------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------|
| Limitations | For diagnostic purposes, the results<br>should always be assessed in<br>conjunction with the patient's<br>medical history, clinical<br>examination and other findings. | |
| | Patients known to be genotypically<br>negative for Lewis blood group<br>antigens will be unable to produce<br>the CA 19-9 antigen even in the<br>presence of malignant tissue.<br>Phenotyping for the presence of<br>the Lewis blood group antigen may<br>be insufficient to detect true Lewis<br>antigen negative individuals. Even<br>patients who are genotype positive<br>for the Lewis antigen may produce<br>varying levels of CA 19-9 as the<br>result of gene dosage effect. | |

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/5/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is a stylized symbol that resembles a caduceus, a traditional symbol of medicine, with three wavy lines representing the branches of the department.

Roche Diagnostics Corp. c/o Ms Kay A. Taylor 9115 Hague Rd. Indianapolis, IN 46250

JUL 6 - 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Re: k050231

Trade/Device Name: Elecsys CA 19-9 Immunoassay Elecsys CA 19-9 CalSet Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: NIG, JIT Dated: January 21, 2005 Received: January 26, 2005

Dear Ms Taylor:

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 either class II (Special Controls) or class III (PMA), 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 898. 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 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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Page 2 –

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, 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" (21CFR Part 807.97). 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,

lobatz Beckerh

Robert L. Becker, Jr., MD, P Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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### Indications for Use

510{k} Number (if known): K050231

Device Name: Elecsys CA 19-9 Immunoassay Elecsys CA 19-9 CalSet

Indications For Use:

#### IMMUNOASSAY

Immunoassay for the in vitro quantitative determination of CA 19-9 turnor associated antigen, in human serum and plasma.

The assay is indicated for the serial measurement of CA 19-9 to aid in the management of patients diagnosed with cancers of the exocrine pancreas. The test is useful as an aid in the monitoring of disease status in those patients having confirmed pancreatic cancer who have levels of CA 19-9 at some point in their disease process exceeding the median concentration determined for the apparently healthy cohort.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 1010/2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay analyzers.

#### CALSET

Elecsys CA 19-9 is used for calibrating the quantitative Elecsys CA 19-9 assay on the Elecsys immunoassay systems. Prescription Use XXX AND/OR Over-The-Counter Use (Part 21 CFR 801 Subpart D) (21 CFR 807 Subpart C)

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

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

Trena Chen

Division Sign-Off

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Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K050251