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.

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria here are implicitly defined by the comparison to the predicate device. The study aims to demonstrate substantial equivalence, meaning the Elecsys CA 19-9 system performs with comparable characteristics to the legally marketed Fujirebio CA 19-9 RIA.

Feature / Acceptance Criteria (vs. Predicate)	Elecsys CA 19-9 Performance (Reported)	Fujirebio CA 19-9 RIA (Predicate Performance)
Intended Use	In vitro quantitative determination of CA 19-9 tumor-associated antigen in serum and plasma.	In vitro quantitative determination of CA 19-9 tumor-associated antigen in serum and plasma.
Indication for Use	An aid in the management of patients with cancers of the exocrine pancreas.	An aid in the management of patients with cancers of the exocrine pancreas.
Assay Principle	Electrochemiluminescent immunoassay	Radioimmunoassay
Sample Type	Human serum and plasma	Human serum and plasma
Measuring Range (Analytical Range)	0.60 - 1000 U/mL	0.9 - 240 U/mL
Precision (Within-run CV) - 1010/2010	2.9%-4.8% CV @ 11.1-185.4 U/mL	Average variability ranged from 6.7% (44 U/mL) to 15.4% (8 U/mL).
Precision (Total Precision CV) - 1010/2010	2.9%-4.4% CV @ 11.1-185.4 U/mL	Average variability ranged from 6.7% (44 U/mL) to 15.4% (8 U/mL).
Precision (Within-run CV) - E170	1.2%-2.5% CV @ 5.2-379 U/mL	Average variability ranged from 6.7% (44 U/mL) to 15.4% (8 U/mL).
Precision (Total Precision CV) - E170	1.9%-8.0% CV @ 5.57-371 U/mL	Average variability ranged from 6.7% (44 U/mL) to 15.4% (8 U/mL).
Analytical Sensitivity (LDL)	0.60 U/mL	0.9 U/mL
Hook Effect	No high dose hook effect up to 500,000 U/mL	None up to 1,250,000 U/mL
Interference (Icterus)	Unaffected by icterus (bilirubin < 1129 µmol/L or < 66 mg/dL)	Not to be performed on icteric samples.
Interference (Hemolysis)	Unaffected by hemolysis (Hb < 1.4 mmol/L or < 2.2 g/dL)	Not to be performed on hemolyzed samples.
Interference (Lipemia)	Unaffected by lipemia (Intralipid < 1500 mg/dL)	Not to be performed on lipemic samples.
Interference (Biotin)	Unaffected by biotin < 100 ng/mL; caution with >5mg/day doses.	(Not explicitly stated for predicate in comparison table)
Interference (Rheumatoid Factors)	No interference from rheumatoid factors up to 1500 IU/mL.	(Not explicitly stated for predicate in comparison table)
Interference (Pharmaceuticals)	No interference found from 27 commonly used pharmaceuticals.	(Not explicitly stated for predicate in comparison table)
Interference (HAMA/Heterophilic antibodies)	Additives minimize effects of monoclonal mouse antibodies; rare interference from antibodies to streptavidin and ruthenium.	May show false elevated/depressed values with HAMA; requires careful evaluation.

Study Proving Device Meets Acceptance Criteria:

The provided text describes a submission for substantial equivalence to a predicate device (Fujirebio Diagnostics CA 19-9 RIA, cleared under K020566). The study is not detailed as a separate clinical trial but through a direct comparison of the performance characteristics of the Elecsys CA 19-9 Immunoassay with the predicate device. The underlying assumption is that if the new device demonstrates comparable or superior performance across these key analytical metrics, it is "substantially equivalent" and thus meets the acceptance criteria for market clearance.

2. Sample Size Used for the Test Set and Data Provenance

The provided text does not explicitly state the sample size used for the various performance characteristic tests (precision, analytical sensitivity, hook effect, interference studies). Similarly, data provenance (country of origin, retrospective/prospective) is not mentioned. This is common for this type of 510(k) summary, as it focuses on the analytical performance values rather than the specific study design details like subject recruitment or data collection methods.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Given this is an in vitro diagnostic (IVD) device for quantitative determination of a biomarker (CA 19-9), the "ground truth" for the test set is established through reference methods or known concentrations of the analyte in control materials or patient samples with confirmed clinical status, rather than expert interpretation of images or other subjective data. Therefore, the concept of "experts establishing ground truth" in the way it applies to image-based diagnostics (e.g., radiologists) is not applicable here. The ground truth would be chemical/analytical, often determined by highly accurate laboratory methods or certified reference materials.

4. Adjudication Method for the Test Set

As this is an IVD device measuring a quantitative biomarker, adjudication by human experts (like 2+1 or 3+1 consensus) is not applicable. The "ground truth" for analytical performance studies is based on established laboratory methods, standard reference materials, or clinically characterized samples, against which the device's measurements are compared.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

No MRMC comparative effectiveness study was done or is applicable here. This study pertains to a standalone in vitro diagnostic immunoassay that quantifies a biomarker. It is not an AI-assisted diagnostic tool for human readers interpreting complex medical data (like images). Therefore, the concept of human readers improving with AI assistance is not relevant to this device.

6. If a Standalone (i.e. algorithm only, without human-in-the-loop performance) Was Done

Yes, a standalone performance assessment was done. The entire summary describes the analytical performance of the Elecsys CA 19-9 Immunoassay as an algorithm-only (device-only) system. Its reported precision, analytical sensitivity, measuring range, and interference characteristics are inherent to the device's technical operation, without direct human intervention in the measurement process itself. The "human-in-the-loop" aspect exists in the medical professional interpreting the quantitative result in the context of a patient's overall clinical picture, but the device's performance metrics are standalone.

7. The Type of Ground Truth Used

The ground truth used for evaluating this immunoassay would be based on:

Known concentrations of CA 19-9 in assayed controls and calibrators.
Reference methods or established laboratory methods for samples used in comparisons (e.g., external quality assessment programs, or comparison to the predicate device).
Clinically characterized patient samples for assessing agreement with clinical status or disease progression (though specific details of such studies are not provided in this summary, the intended use implies this clinical correlation).
The summary itself primarily focuses on analytical performance against established laboratory standards and comparisons to the predicate device.

8. The Sample Size for the Training Set

The document does not provide information on a specific "training set" sample size. For an immunoassay like this, the development process involves extensive internal validation and optimization, but the concept of a distinct "training set" as understood in machine learning (where algorithms learn from data) does not directly apply in the same way. The performance characteristics described are the result of the device's engineering and chemical design, validated against samples to establish its specifications.

9. How the Ground Truth for the Training Set Was Established

Since a "training set" in the machine learning sense is not explicitly referenced or described for this immunoassay, information on how its ground truth was established is not available in the provided text. The development of such an immunoassay involves optimizing reagents, reaction conditions, and calibration procedures to accurately measure CA 19-9. This optimization would rely on accurately prepared samples with known CA 19-9 concentrations, established through internal reference methods and material characterization.

Summary

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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 Diagnostics9115 Hague RoadIndianapolis, IN 46250(317) 521-3544Contact Person: Kay A. Taylor
Device Name	Proprietary name:	Elecsys CA 19-9 ImmunoassayElecsys CA 19-9 CalSet
	Common name:	Immunological test for CA 19-9 antigenCalibrator
	Classification name:	System, Test, Carbohydrate Antigen (CA 19-9), for monitoring and management of Pancreatic CancerCalibrator, 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.

Substantialequivalence -comparison	The following table compares the Roche Elecsys CA 19-9 Immunoassay withthe predicate device.
--------------------------------------------	--------------------------------------------------------------------------------------------------

Feature	Elecsys CA 19-9	Fujirebio CA 19-9 RIA(predicate)
Intended Use	In vitro quantitativedetermination of CA 19-9 tumor-associated antigen in serum andplasma.	In vitro quantitativedetermination of CA 19-9tumor-associated antigen inserum and plasma.
Indication for Use	An aid in the management ofpatients with cancers of theexocrine pancreas.	An aid in the management ofpatients with cancers of theexocrine pancreas.
Assay Principle	Electrochemiluminescentimmunoassay	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(predicate)
Calibrator	Elecsys CA 19-9 CalSet (2levels)	CA 19-9 Standard set (6 levelsincluding 0)
Controls	PreciControl Tumor Marker (2level)	Defibrinated human plasmacontaining 2 levels of Ca 19-9
Instrument	Elecsys 1010, 2010 andMODULAR ANALYTICS E170	Manual method or semi-automated with commerciallyavailable 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(predicate)
Precision	1010/2010Within-run2.9%-4.8% CV @ 11.1-185.4 U/mLTotal Precision2.9%-4.4% CV @ 11.1-185.4 U/mLE170Within-run1.2%-2.5% CV @ 5.2-379 U/mLTotal Precision1.9%-8.0% CV @ 5.57-371 U/mL	Average variability ranged from6.7% (44 U/mL) to 15.4% (8 U/mL).
Analyticalsensitivity (LDL)	0.60 U/mL	0.9 U/mL
Hook Effect	No high dose hook effect up to500,000 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(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(predicate)
Limitations	For diagnostic purposes, the resultsshould always be assessed inconjunction with the patient'smedical history, clinicalexamination and other findings.
	Patients known to be genotypicallynegative for Lewis blood groupantigens will be unable to producethe CA 19-9 antigen even in thepresence of malignant tissue.Phenotyping for the presence ofthe Lewis blood group antigen maybe insufficient to detect true Lewisantigen negative individuals. Evenpatients who are genotype positivefor the Lewis antigen may producevarying levels of CA 19-9 as theresult 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 (240) 276-0484. 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 (800) 638-2041 or (301) 443-6597 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 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

Page 1 of

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K050251

Regulation Number and Section

§ 862.1150 Calibrator.

(a)
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.)(b)
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.