The Vitros® PSA is an in vitro assay intended for the quantitative measurement of prostate specific antigen (PSA) in human serum or plasma (EDTA or heparin) to aid in the management of patients with prostate cancer.

Device Description

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum, plasma or urine. Coated microwells are used as the solid phase separation system.

The system is comprised of three main elements:

The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products PSA Reagent Pack, VITROS Immunodiagnostic Products PSA Calibrators, which are combined by the VITROS Immunodiagnostic System to perform the VITROS PSA assay).
The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits.
Common reagents used by the VITROS System in each assay.

AI/ML Overview

Here's an analysis of the provided text regarding the VITROS® Immunodiagnostic Products PSA assay, focusing on acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The submission doesn't explicitly define formal "acceptance criteria" in a table format with specific numerical targets. Instead, the demonstration of substantial equivalence is the primary acceptance criterion, and this is shown through comparison with a predicate device across various performance aspects.

Device Characteristic	Predicate Performance (Hybritech Tandem-R PSA)	VITROS PSA assay Performance	Acceptance (Substantial Equivalence)
Calibration Range	0 - 100 ng/mL	0 - 100 ng/mL	Equivalent
Basic Principle	Solid phase immunoradiometric assay	Solid phase immunoassay	Similar (both solid phase immunoassay)
Sample Type	Serum	Serum, plasma (heparin or EDTA)	Similar (expanded for plasma)
Antibody	1) Mouse monoclonal anti-PSA antibody coated onto plastic beads 2) Radiolabeled mouse monoclonal anti-PSA in protein matrix	1) Two mouse monoclonal anti-PSA antibodies in biotinylated antibody reagent 2) Goat polyclonal anti-PSA antibody in conjugate reagent	Different (but both anti-PSA antibodies)
Sample Volume	50 uL	15 uL	Different (VITROS uses less sample)
Analytical Sensitivity	0.1 ng/mL	0.02 ng/mL	Better (VITROS is more sensitive)
Correlation with Predicate Device	N/A	Correlation Coefficient: 0.989	Strong correlation
Regression Equation (VITROS vs. Predicate)	N/A	VITROS PSA assay = 1.028 x [the Tandem-R PSA assay] -- 0.089 (ng/mL)	Close to 1:1 relationship
Clinical Equivalence in various patient types (normal, malignant, non-malignant diseases)	Expected distributions	Exhibited distribution results that parallel expected distributions	Equivalent
Serial monitoring in treated prostate cancer patients	Substantially equivalent	Demonstrated substantial equivalence	Equivalent

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

The exact sample sizes for the various comparative tests are not explicitly stated in the provided text. The document mentions:

"Comparisons of the VITROS PSA assay and the predicate device were performed with samples from a variety of clinical categories."
"In clinical studies of apparently healthy individuals, patients with malignant disease and patients with a variety of non-malignant diseases..."
"The serial monitoring study demonstrated that the VITROS PSA assay is substantial equivalent to the predicate device in patients previously treated for prostate cancer."

Data Provenance: The data is retrospective, relying on "patient specimens" and "currently commercially available reagents" (for the predicate device). The country of origin is not specified, but the submission is to the FDA, suggesting a US-centric regulatory context.

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

This information is not provided in the text. As this is an in vitro diagnostic (IVD) assay for quantitative measurement of PSA, the "ground truth" would likely be the quantitative values obtained from the predicate device (Hybritech Tandem-R PSA) as the reference, rather than expert consensus on image interpretation or clinical diagnosis. The predicate device itself (which was FDA-approved) serves as the established gold standard for comparison.

4. Adjudication Method for the Test Set

This information is not applicable/provided. Adjudication methods (like 2+1 or 3+1) are typically used in studies involving human interpretation of diagnostic results (e.g., radiology, pathology) to establish a consensus ground truth. For a quantitative IVD assay like PSA, the ground truth is a numerical value, and the comparison is statistical (correlation, regression) rather than based on expert consensus of discrete diagnostic labels.

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

This information is not applicable. This submission describes an in vitro diagnostic assay, not an AI-assisted diagnostic tool that would be used by human readers (e.g., radiologists, pathologists) to interpret complex data. Therefore, an MRMC study and effects on human reader performance are not relevant to this device.

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

Yes, this study represents a standalone performance evaluation of the VITROS PSA assay. The device itself (the immunoassay system) produces a quantitative result, and its performance is assessed against an established predicate device. There is no human interpretation or human-in-the-loop component being evaluated for improvement.

7. The Type of Ground Truth Used

The primary "ground truth" for the test set is the quantitative measurement of PSA obtained from the predicate device, Hybritech Tandem-R PSA. This is implied by the extensive comparison using Bablock Passing regression, which calculates the relationship between the new device's readings and the predicate's readings. The predicate device itself serves as the reference standard for established diagnostic values.

8. The Sample Size for the Training Set

The document does not explicitly state any "training set sample size" or a clear distinction between training and test sets in the modern machine learning sense. For an immunoassay, the development process (which could be analogous to "training") would involve extensive R&D, optimization, and characterization using various reagent lots, controls, and calibration materials, rather than a distinct "training set" of patient data for an algorithm. The submitted data focuses on the validation or test set performance against the predicate.

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

As there's no explicitly defined "training set" in the context of an algorithm, the concept of establishing ground truth for it doesn't directly apply. The immunoassay itself is designed and optimized based on known biochemical principles and analytical performance targets. The "ground truth" for developing the assay would involve purified PSA standards, established reference methods, and internal characterization studies to ensure accurate and precise measurement.

Summary

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ADMINISTRATIVE 1

1.1 510(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: K984889

1. Submitter name, address, contact

Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 (716) 453-3607

Contact Person: Anne Zavertnik

Date 510(k) prepared: November 30, 1998

2. Device Name

Trade or Proprietary Name: VITROS® Immunodiagnostic Products PSA Calibrators VITROS® Immunodiagnostic Products PSA Reagent Pack

Common Name: PSA assay

Classification Name: test for the in vitro quantitative determination of prostate specific antigen in serum or plasma.

3. Predicate Device

The VITROS Immunodiagnostic Products PSA assay is substantially equivalent to the Hybritech Tandem®-R PSA (P850048).

4. Device Description

The system is comprised of three main elements:

1. The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products PSA Reagent Pack, VITROS Immunodiagnostic Products PSA Calibrators, which are combined by the VITROS Immunodiagnostic System to perform the VITROS PSA assay).

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1. The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
1. Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 510(k) pre-market notification (K984310).

The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.

5. Device Intended Use

6. Comparison to Predicate Device

The VITROS Immunodiagnostic Products PSA assay is substantially equivalent to Hybritech Tandem-R PSA (predicate device), which was approved by FDA (P850048) for IVD use.

The relationship between the VITROS PSA assay and the predicate device, determined by Bablock Passing, is:

VITROS PSA assay = 1.028 x [the Tandem-R PSA assay] -- 0.089 (ng/mL), with a correlation coefficient of 0.989.

Comparisons of the VITROS PSA assay and the predicate device were performed with samples from a variety of clinical categories.

In addition to the studies mentioned above, tests were performed to obtain analytical sensitivity, specificity, precision, dilution and expected values. Refer to the VITROS PSA assay package insert for VITROS PSA assay results.

Table 1 lists the similarities and differences of the device characteristics between the VITROS PSA assay with the predicate device:

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DeviceCharacteristic	VITROS PSA assay	PredicateDevice
Calibration range	0 - 100 ng/mL	0 - 100 ng/mL
Basic principle	Solid phase immunoassay	Solid phaseimmunoradiometric assay
Sample type	Serum, plasma (heparin orEDTA)	Serum
Antibody	l) Two mouse monoclonalanti-PSA antibodies inbiotinylated antibodyreagent	l) Mouse monoclonalanti-PSA antibody coatedonto plastic beads
	2) Goat polyclonal anti-PSA antibody in conjugatereagent	2) Radiolabeled mousemonoclonal anti-PSA inprotein matrix
Sample volume	15 uL	50 uL
Analytical sensitivity	0.02 ng/mL	0.1 ng/mL

Table 1 List of the assay characteristics

7. Conclusions

The data presented in the premarket notification demonstrate that the VITROS PSA assay performs substantially equivalent to the approved predicate device.

Equivalence was demonstrated using currently commercially available reagents along with patient specimens from patients who are normal, undergoing therapeutic and/or undergoing diagnostic evaluation. In clinical studies of apparently healthy individuals, patients with malignant disease and patients with a variety of non-malignant diseases, the VITROS PSA assay exhibited distribution results that parallel expected distributions for these patient types.

The serial monitoring study demonstrated that the VITROS PSA assay is substantial equivalent to the predicate device in patients previously treated for prostate cancer.

The data presented in the premarket notification provide a reasonable assurance that the VITROS PSA assay is safe and effective for the stated intended use.

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Image /page/3/Picture/1 description: The image is a black and white seal for the Department of Health & Human Services - USA. The seal is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal are three stylized figures that appear to be birds or abstract human figures. The figures are arranged in a vertical stack, with the top figure being the largest and the bottom figure being the smallest.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAR 1 2 1999

Anne Zavertnik Regulatory Affairs Associate Ortho-Clinical Diagnostics 100 Indigo Creek Drive Rochester NY 14626-5101

Re: K984289

Trade Name: VITROS Immunodiagnostic Products PSA Calibrators VITROS Immunodiagnostic Products PSA Reagent Pack Regulatory Class: II Product Code: LTJ Dated: February 26, 1999 Received: March 1, 1999

Dear Ms. Zavertnik:

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 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). 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 Current Good Manufacturing Practice requirements, 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 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.

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Page 2

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 Autman

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

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Page 1 of 1

1.2 Indications For Use Statement

510(k) Number (if known):

Device Name:

VITROS Immunodiagnostic Products PSA Reagent Pack VITROS Immunodiagnostic Products PSA Calibrators

1484289

Indications for Use:

Tita E. Makeri
(Division Sign Off)

(Division Sign-Off) (Division Sign of Clinical Laboratory Dev 84289 510(k) Number

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109) OR

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.