The Access® PSA assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of prostate-specific antigen (PSA) in human serum using the ACCESS Immunoassay System. PSA measured by the Access PSA Immunoassay, is used as an aid in the management of patients with prostate cancer.

Device Description

The ACCESS® PSA Immunoassay Reagents and the ACCESS® Immunoassay Analyzer comprise the ACCESS® Immunoassay System for the quantitative determination of PSA in human serum.

AI/ML Overview

The provided document describes a 510(k) submission for the ACCESS® PSA Assay, which is intended for quantitative determination of Prostate-Specific Antigen (PSA) in human serum and for use as an aid in the management of patients with prostate cancer. The acceptance criteria and supporting studies are presented in comparison to a predicate device, the Tandem®-R PSA assay.

Here's a breakdown of the requested information:

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in a quantitative manner for all parameters, but rather demonstrates performance by comparing to a predicate device and presenting observed results. For the purpose of this analysis, the "reported device performance" are the results achieved in the described studies, implying these met the implicit acceptance criteria for substantial equivalence to the predicate device.

Acceptance Criteria Category	Reported Device Performance (ACCESS® PSA Assay)
Correlation	r = 0.994 (vs. Tandem®-R PSA assay)
	y = 1.01x - 0.96 (regression equation vs. Tandem®-R PSA assay)
Expected Range	97.5% <= 4.0 ng/ml inapparently healthy males; 2.5% in 4-10 ng/ml range
Monitoring Data Concordance	Highly concordant with Tandem®-R PSA results and clinical assessment
Recovery (Dilution)	Average recovery: 98.4% (Range: 94.9% to 105.4%)
Recovery (Spike)	Average recovery: 99.0% (Range: 95.2% to 104%)
Intra-assay Imprecision	Ranged from 1.29% CV to 2.35% CV
Inter-assay Imprecision	Ranged from 1.33% CV to 3.10% CV
Total Imprecision	Less than 5% at PSA levels 0.32 to 81.58 ng/ml
Specificity	No significant interference from tested contaminants and therapeutic drugs
Analytical Sensitivity	Lowest detectable level: 0.013 ng/ml (with 95% confidence)

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

Correlation: 293 samples
Expected Range: Population of apparently healthy males (exact number not specified)
Monitoring Data: 127 monitoring samples from a total of 29 previously diagnosed prostate cancer patients.

Data Provenance: The document does not explicitly state the country of origin. It is a retrospective analysis from "previously diagnosed prostate cancer patients" for monitoring data and "a population of apparently healthy males" for expected range. For correlation, it involved samples "run with both the ACCESS® PSA Immunoassay and the Tandem®-R PSA assay," implying collected samples.

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

The document does not specify the number or qualifications of experts used to establish ground truth for the test set.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set. The clinical assessment mentioned for monitoring data would inherently involve expert opinion, but no specific adjudication process (e.g., 2+1) is detailed.

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

No. This document does not describe an MRMC comparative effectiveness study involving human readers. It focuses on the analytical performance of the assay itself compared to a predicate device and clinical assessment, not on how human interpretation of results might be improved with or without AI assistance.

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

Yes. The studies described are standalone performance evaluations of the ACCESS® PSA Immunoassay system. The results presented (correlation, expected range, recovery, precision, specificity, analytical sensitivity) characterize the sensor/algorithm performance directly without human-in-the-loop interaction in the measurement itself. The "monitoring data" section notes that results were compared to "concurrent clinical assessment or predicted the subsequent clinical assessment," which reflects the assay's utility in a clinical context, but the assay itself is standalone.

7. The Type of Ground Truth Used

Correlation: The predicate device (Tandem®-R PSA assay) served as the reference standard for comparison.
Expected Range: Statistical distribution within a defined population of "apparently healthy males."
Monitoring Data: Reference was against the predicate device's results and "concurrent clinical assessment or predicted the subsequent clinical assessment," implying clinical diagnosis/progression as determined by clinicians.
Recovery/Precision/Specificity/Analytical Sensitivity: These are intrinsic analytical performance measures, where "ground truth" is established by controlled experiments (e.g., known spikes of PSA, defined sample matrices for specificity).

8. The Sample Size for the Training Set

The document does not provide details about a specific "training set" or its size. This is a 510(k) submission for an in-vitro diagnostic device, not typically a machine learning algorithm that undergoes traditional "training" in the same sense. The development and validation phases would involve various samples used for assay optimization and calibration, but these are not explicitly referred to as a "training set" in this context.

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

As noted above, the concept of a "training set" for a machine learning algorithm with established ground truth is not explicitly applicable here. For the development and calibration of the immunoassay, ground truth would have been established through:

Known concentrations: For calibrators and controls used to create standard curves and validate linearity.
Reference materials: Utilizing certified reference materials or highly characterized samples for method development and optimization.
Comparison to reference methods: Performance during development would be benchmarked against existing, established PSA measurement techniques.

Summary

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i i i 16 16

Summary of Safety and Effectiveness

FEB 20 1998

Prepared December 19, 1997

1. General Information Device Generic Name:
  K974816

Prostate Specific Antigen (PSA) Immunological Test System for Management of Prostate Cancers

Device Trade Name:

Applicant's Name and Address:

Beckman Instruments, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

ACCESS® PSA Assay

Contact Person:

Ellen Voss. M.S.

2. Predicate Device

Tandem®-R PSA Immunoradiometric Assay Hybritech, Inc. P. O. Box 269006 San Diego, CA 92196-9006

PMA Number: P850048

3. Device Description

The ACCESS® PSA Immunoassay Reagents and the ACCESS® Immunoassay Analyzer comprise the ACCESS® Immunoassay System for the quantitative determination of PSA in human serum.

4. Indications for Use

The ACCESS® PSA Immunoassay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of prostate-specific antigen (PSA) in human serum using the ACCESS® Immunoassay System. PSA. measured by the ACCESS® PSA Immunoassay, is intended for use as an aid in the management of patients with prostate cancer.

5. Comparison of Technological Characteristics

Both the ACCESS® PSA Immunoassay and the Tandem®-R PSA assay quantitatively measure serum PSA by means of simultaneous immunoassays utilizing the binding of PSA to monoclonal antibodies specific to similar epitopes on the PSA molecule. Both systems measure complexed and free forms of PSA equally. Both systems utilize liquid multi-point calibrators.

The ACCESS® PSA Immunoassay Reagents are designed for use on the ACCESS® Immunoassay Analyzer, a fully automated, random access system, while the Tandem®-R PSA assay is a manual method. The ACCESS® Immunoassay Analyzer uses magnetic particle solid phase enzyme immunoassays with chemiluminescent measurement, while the Tandem®-R PSA assay uses a plastic bead solid support with radioactive labeling and detection. The ACCESS® Immunoassay Analyzer stores reagents on board for up to 24 different analytes and has 28 day calibration curve stability, while Tandem®-R PSA assay is an individual analyte reagent kit requiring a new calibration with each assay.

6. Summary of Studies

Correlation: A comparison of PSA values from 293 samples, ranging from 0.0 to 150.0 ng/ml, run with both the ACCESS® PSA Immunoassay and the Tandem®-R PSA assav

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demonstrated very good agreement with the following statistical data: r = 0.994; v = 1.01x - 0.96.

Expected Range: In a population of apparently healthy males, 97.5% had PSA values of 4.0 ng/ml or less, with the remaining 2.5% having values in the 4 to 10 ng/ml range.

Monitoring Data: 127 monitoring samples (4 to 6 longitudinal samples per patient) from a total of twenty-nine (29) previously diagnosed prostate cancer patients were compared on the ACCESS® PSA and Tandem®-R PSA assays to verify the intended use claim for monitoring. The data demonstrate that the ACCESS® PSA results were highly concordant to both the Tandem®-R PSA results and the concurrent clinical assessment or predicted the subsequent clinical assessment.

Recovery: Linearity studies performed by diluting human serum samples with ACCESS® PSA Sample Diluent provided an average recovery of 98.4%, with individual recoveries ranging from 94.9 to 105.4%. Recovery of exogenous PSA spiked into serum samples resulted in an average recovery of 99.0%, with individual recoveries ranging from 95.2 to 104%.

Precision: Intra-assay imprecision ranged from 1.29% CV to 2.35% CV. Inter-assay imprecision ranged from 1.33% CV to 3.10% CV. Total impression was less than 5% at PSA levels ranging from 0.32 to 81.58 ng/ml.

Specificity: There was no significant interference from potential sample contaminants (albumin, bilirubin, HAMA, hemoglobin, PAP and triglycerides) or therapeutic drugs (acetamidophenol. acety)salicyclic acid. cisplatin, cyclophosphamide acid, doxorubicin, methotrexate, phenacetin, and vinblastin).

Analytical Sensitivity: The lowest detectable level of PSA distinguishable from zero (ACCESS® PSA Calibrator S0) with 95% confidence is 0.013 ng/ml.

7. Conclusion

The ACCESS® PSA Immunoassay Reagents, when used in conjunction with the ACCESS® Immunoassay Analyzer, are substantially equivalent to the Tandem®-R PSA test system. The ACCESS® PSA Immunoassay is appropriate for monitoring patients with prostate cancer.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 20 1998

Ms. Ellen Voss, M.S. Clinical and Regulatory Associate Beckman Instruments, Inc. Immunodiagnostic Development Center 1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084

Re : K974816 Trade Name: ACCESS® PSA Assay Regulatory Class: II Product Code: LTJ Dated: December 18, 1997 Received: December 23, 1997------

Dear Ms. Voss:

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 aqainst 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 regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. 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.

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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 labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and 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 Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and : 上一 Radiological Health

Enclosure

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INDICATIONS FOR USE STATEMENT

510(k) Number (if known):K974816

Page 1 of 1

Device Name: ACCESS® PSA

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Peter E. Martin

Prescription Use
(Per 21 CFR 801.109)

Over-The Counter Use

(Optional Format 1-2-96)

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.