The Access GI Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 19-9 antigen levels in human serum and plasma using the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 19-9 antigen to aid in the management of pancreatic cancer patients. The test is useful as an aid in monitoring of disease status in those patients having confirmed pancreatic cancer whose serum CA 19-9 antigen levels exceed 10 U/mL, the cut-off value for individuals who are Lewis blood group antigen negative. Serial testing for patient CA 19-9 antigen concentrations should be used in conjunction with other clinical methods used for monitoring pancreatic cancer.

Device Description

The Access GI Monitor reagents, calibrators, and the Access Immunoassay Analyzers (Access, Access 2, Synchron LXi 725, and UniCel Dxl 800) comprise the Access Immunoassay Systems for the quantitative determination of CA 19-9 antigen in human serum and plasma.

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

Acceptance Criteria / Performance Metric	Reported Device Performance
Imprecision:
- Within-run CV	1.7% CV to 6.4% CV
- Within-laboratory CV	2.4% CV to 5.7% CV
- Total Imprecision CV	3.0% CV to 8.9% CV
Analytical Sensitivity:	0.8 U/mL
Dilution Recovery (Linearity):	Average recovery of 96% (ranging from 93% to 100%)
Methods Comparison (with predicate):	y = 0.9569x + 2.5726, r = 0.9007
Sample Type Comparison (Serum vs. Plasma):	y = 0.9842x - 0.5002, r = 0.9995
Analytical Specificity:	No significant interference from therapeutic drugs, similar compounds, or common sample contaminants (bilirubin, hemoglobin, triglycerides, human serum albumin, rheumatoid factor).
Reagent Stability (opened):	56 days
Calibrator Stability (opened):	90 days
Calibration Curve Stability:	56 days
Clinical Sensitivity (relative to predicate):	96.6%
Clinical Specificity (relative to predicate):	94.6%
Agreement (with predicate):	95.1%

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

Imprecision: Not explicitly stated, but concentrations ranged from approximately 17 to 1665 U/mL. The study involved running samples to establish within-run, within-laboratory, and total imprecision.
Dilution Recovery (Linearity): 6 human samples were diluted.
Methods Comparison: 405 samples were used, ranging from 0.0 to 236.0 U/mL.
Sample Type Comparison: 80 matched serum and lithium heparin plasma samples, ranging from 0.0 to 1650.9 U/mL.
Clinical Studies (Reference Limit): The "apparently healthy subject population" was used to establish the 95th percentile (35 U/mL CA 19-9) as the upper reference limit. The size of this population is not specified.
Clinical Studies (Pancreatic Cancer Monitoring): Patients diagnosed with pancreatic cancer were monitored. The number of patients is not specified.
Clinical Studies (Sensitivity/Specificity): "Pancreatic cancer monitoring subjects" were used. The number of subjects is not specified.

Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective for any of the studies. However, the mention of "human Dildion Nooorory (evels" (likely meant to be "human dilution recovery levels") and "human serum and plasma" samples suggests human biological samples were used.

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

The document does not mention the use of experts to establish ground truth for the test set. Instead, the performance evaluations (imprecision, linearity, specificity, methods comparison, sample type comparison, stability) rely on laboratory measurements and comparisons to a predicate device. The clinical studies compare the device's performance to the predicate device's performance in terms of monitoring patient status and determining relative sensitivity and specificity.

4. Adjudication Method for the Test Set

No adjudication method is mentioned as the studies are primarily analytical performance assessments and comparisons to a predicate device, rather than studies requiring expert consensus on outputs.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) immunoassay, not an imaging or diagnostic device that involves human readers interpreting results.

6. If a Standalone Performance (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies described are all "standalone" in the sense that they evaluate the performance of the immunoassay system (reagents, calibrators, and analyzer) itself, without direct human interpretation of the assay results as part of the performance metrics. The results (CA 19-9 levels) are quantitative measurements produced by the automated system.

7. The Type of Ground Truth Used

Analytical Studies:
- Imprecision, Analytical Sensitivity, Dilution Recovery, Stability, Analytical Specificity: The "ground truth" for these studies is inherent in the design of the experiments, where known concentrations of analytes, controlled dilutions, or specific interfering substances are used to assess the device's ability to accurately and reproducibly measure CA 19-9.
- Methods Comparison: The "ground truth" is the established predicate device (Fujirebio Diagnostics CA 19-9 RIA assay). The new device's measurements are compared to those of the predicate.
- Sample Type Comparison: The "ground truth" is the agreement between a person's serum and plasma samples when measured by the same device.
Clinical Studies:
- Reference Limit: The "ground truth" is derived from the distribution of CA 19-9 levels in purportedly "healthy" individuals which establishes a statistical reference.
- Pancreatic Cancer Monitoring: The "ground truth" for assessing monitoring effectiveness appears to be the observed clinical course of pancreatic cancer patients and how the device's CA 19-9 measurements "paralleled results obtained with the predicate device."
- Sensitivity/Specificity: The "ground truth" is derived from diagnosed pancreatic cancer patients and the reference ranges (URL) for both the new device and the predicate device, implying comparison to a clinical diagnosis (presumed true positive/negative status) as well as the predicate device's established performance.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning. This device is an immunoassay, the development of which typically involves extensive R&D and optimization (which could be considered analogous to training) but is not usually described with a distinct "training set" in the same way as AI/ML algorithms. The analytical and clinical studies described are for the performance evaluation of the finalized device.

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

As explained above, there isn't a "training set" in the common AI/ML sense presented in this document. The development and optimization of the immunoassay would have involved chemical and biological principles to ensure accurate binding, detection, and quantification of the CA 19-9 antigen. The ground truth for such development would involve precise measurements of known antigen concentrations, characterized antibodies, and optimized reaction conditions.

Summary

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510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: Ko3303 8

Submitter's Name and Address

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318 Telephone: (952) 368-1323 Fax: (952) 368-7610 Contact: Brent Taber

Date Prepared: December 8, 2003

Device Names

Proprietary Name:	GI Monitor and GI Monitor Calibrators on theAccess® Immunoassay Systems
Common Name:	Immunological test for 116NS19-9 Antibody DefinedAntigen (CA19-9)
Classification Name:	System, Test, Carbohydrate Antigen (CA 19-9), forMonitoring and Management of Pancreatic Cancer

Predicate Device

Fujirebio Diagnostics CA 19-9 RIA Fujirebio Diagnostics, Inc. 201 Great Valley Parkway Malvern, PA 19355

510(k) Number:

Device Description

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Intended Use

The Access GI Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 19-9 antigen levels in inimonodouly Tor the qualisian the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 19-9 antigen to aid in the management of pancreatic cancer patients. The test is useful as an aid in monitoring of disease status in those patients having confirmed pancreatic cancer whose serum CA 19-9 antigen levels exceed 10 U/mL, the cut-off value for individuals who are Lewis blood group antigen negative. Serial testing for patient CA 19-9 antigen concentrations should be used in conjunction with other clinical methods used for monitoring pancreatic cancer.

Attribute	Fujirebio DiagnosticsCA 19-9 RIA	Access GI Monitor
IntendedUse	For the measurement ofCA 19-9 antigen in humanserum and plasma	For the measurement ofCA 19-9 antigen in humanserum and plasma
AssayPrinciples	Utilizes the binding of CA 19-9to a specific monoclonalantibody in a manual, two-site"sandwich" radioimmunoassay;Utilizes $^{125}I$ conjugated tomonoclonal antibody	Utilizes the binding of CA 19-9to a specific monoclonalantibody in an automated, two-site "sandwich"enzymeimmunoassay;Utilizes alkaline phosphataseenzyme conjugated tomonoclonal antibody
SolidSupport	Polystyrene beads	Paramagnetic particles
DetectionSystem	Utilizes $^{125}I$ conjugated tomonoclonal antibody;Measures bound radioactivitywith a gamma counter	Utilizes dioxetane-basedchemiluminescent substrate;Measures light production froma chemiluminescent reaction
Calibrators	Liquid calibrators preparedfrom defibrinated normalhuman plasma with CA 19-9antigen at specified levels	Liquid calibrators preparedfrom buffered bovine serumalbumin matrix with CA 19-9antigen at specified levels

Comparison of Technological Characteristics

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Image /page/2/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a circular graphic on the left and the company name on the right. The graphic is a black circle with a white design inside, resembling two curved shapes intertwined. The text "BECKMAN COULTER" is written in a bold, sans-serif font, with "BECKMAN" stacked above "COULTER".

Summary of Analytical Studies

Imprecision: Imprecision was tested for concentrations from approximately 17 to 1665 U/mL. The within run imprecision ranged from 1.7% CV to 6.4% CV. 1000 Chile. The willim ranged from 2.4% CV to 5.7% CV. Total imprecision ranged from 3.0% CV to 8.9% CV.

Analytical Sensitivity: The lowest detectable level of CA 19-9 antigen distinguishable from zero (Access GI Monitor Calibrator S0) is 0.8 U/mL.

Dilution Recovery (Linearity): Linearity studies performed by diluting 6 human Dildion Nooorory (evels with Access GI Monitor S0 Calibrator provided oon average recovery of 96%, with mean percent recoveries ranging from 93% to 100%.

Methods Comparison: A comparison of CA 19-9 antigen values from 405 samples, ranging from 0.0 to 236.0 U/mL, run with both the Access GI Monitor assay and the Fujirebio Diagnostics CA 19-9 RIA assay demonstrated acceptable agreement with the following statistical data: y = 0.9569x + 2.5726, r = 0.9007.

Sample Type Comparison: A comparison of 80 matched serum and lithium heparin plasma samples, ranging from 0.0 to 1650.9 U/mL, using the Access nopani placema campa the following statistical data using Deming calculations: v = 0.9842x - 0.5002, r = 0.9995.

Analytical Specificity: There was no significant interference from therapeutic drugs or similar compounds in the Access GI Monitor assay. In addition, there was no significant interference from potential sample contaminants (bilirubin, hemoglobin, triglycerides, human serum albumin, and rheumatoid factor).

GI Monitor reagents are stable for 56 days after opening and Stability: calibrators are stable for 90 days after opening. The calibration curve is stable for 56 days.

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Image /page/3/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a stylized circular graphic on the left, resembling a stylized eye or a swirling pattern. To the right of the graphic, the words "BECKMAN" are stacked on top of the word "COULTER" in a bold, sans-serif font. The overall design is simple and modern, with a focus on the company name and a distinctive visual element.

Summary of Clinical Studies

The 95th percentile (35 U/mL CA 19-9) for the apparently healthy subject The 90 - percentile (00 - onliner reference limit (URL) for the Access GI Monitor population was out as the apper es Gl Monitor values for apparently healthy assay. The diothbations with various non-malignant and malignant conditions are consistent with results provided in the predicate device labeling.

Results from subjects who were diagnosed with pancreatic cancer and who were monitored over the course of disease demonstrate that CA 19-9 concentrations monitored with the Access GI Monitor assay paralleled results obtained with the predicate device.

Based on the pancreatic cancer monitoring subjects, the relative sensitivity and Belou on the partificity, based on the respective URLs for the Access GI Monitor relative opodifishy, budget the predicate device (URL = 37 U/mL), were 96.6% assuy (ONE - 80 Child) aThe % agreement between the two assays was 95.1%.

Conclusion

GI Monitor and GI Monitor Calibrators on the Access Immunoassay Systems is Of Monitor and Of Ment to Fujirebio Diagnostics CA 19-9 RIA for the measurement of CA 19-9 antigen in human serum and plasma.

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DEC 2 9 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Brent Taber Senior Regulatory Specialist Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318-1084

K033038 Re:

Trade/Device Name: GI Monitor and GI Monitor Calibrators on the Access Immunoassay Systems Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor associated antigen immunological test system Regulatory Class: Class II Product Code: NIG; JIT Dated: December 8, 2003 Received: December 9, 2003

Dear Mr. Taber:

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 vour 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 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 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

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 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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known):

GI Monitor and GI Monitor Calibrators on the Device Name: Access Immunoassay Systems

Indications For Use:

The Access G1 Monitor assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of CA 19-9 antigen levels in human serum and plasma using the Access Immunoassay Systems. This device is indicated for use in the measurement of CA 19-9 antigen to aid in the management of pancreatic cancer patients. The test is useful as an aid in monitoring of disease status in those patients having confirmed pancreatic cancer whose serum CA 19-9 antigen levels exceed 10 U/mL. the cut-off value for individuals who are Lewis blood group antigen negative. Serial testing for patient CA 19-9 antigen concentrations should be used in conjunction with other clinical methods used for monitoring pancreatic cancer.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Maria M Chan

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety Over-The Counter Use__________________________________________________________________________________________________________________________________________________________

Prescription Use_ ✔ (Per 21 CFR 801.109)

510(k)_Ko33038

(Optional Format 1-2-96) Page 32

Regulation Number and Section

§ 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.