The Bayer ADVIA® IMS cPSA assay is an in vitro diagnostic device intended to quantitatively measure complexed prostate specific antigen (cPSA) in human serum. This assay is indicated for the measurement of serum complexed PSA as an aid in management (monitoring) of prostate cancer patients. Complexed PSA values obtained using the Bayer ADVIA IMS assay method must be interpreted in conjunction with all other available clinical and laboratory data before a medical decision is determined.

Device Description

Prostate Specific Antigen (PSA) is a secretory product of the epithelial cells of human prostatic tissue, whether normal, benign, or malignant. The tissue specificity of PSA makes it a sensitive and specific tumor marker as an aid in management (monitoring) prostate cancer patients and disease progression following surgery or other therapies. PSA in serum exists in several forms including free, uncomplexed PSA and PSA complexed to several protease inhibitors including a-2-macroglobulin, a-1antichymotrypsin (ACT), and a-1-antitrypsin. It should be noted that there are no existing commercial methods that can recognize PSA bound to α-2-macroglobulin. However, it has been demonstrated that the proportion of PSA complexed with ACT increases as a function of the total PSA concentration, and that the majority of immunoreactive PSA in cancer patients is in complex with ACT. The Bayer cPSA Assay uses a monoclonal antibody for capture which recognizes both free and complexed PSA, but which, when bound to free PSA, precludes the binding of other antibodies specific for the free form of PSA. The inclusion of a second, unlabelled monoclonal antibody which is specific for free PSA prevents the binding of free PSA in the cPSA assay and allows measurement of only PSA which is complexed with ACT. cPSA can be used as a single test alternative to free and total PSA in management of patients with CaP.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the Bayer ADVIA® IMS cPSA assay, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

Acceptance Criterion	Reported Device Performance (ADVIA IMS cPSA Assay)
Imprecision (Total %CV)
Low cPSA Level (~3.5 ng/mL)	3.0%
Mid cPSA Level (~15.5 ng/mL)	3.4%
High cPSA Level (~77.2 ng/mL)	3.8%
Correlation with Predicate Device (Immuno 1)
Regression Equation (Y = ADVIA IMS, X = Immuno 1)	$0.988 * X - 0.191$ (N=98)
	$1.004 * X - 0.336$ (N=45)
Syx (ng/mL)	0.706 (N=98)
	0.566 (N=45)
R	0.999 (both N=98 and N=45 sets)
Sample Range (ng/mL)	0.14-86.28 (N=98)
	0.03-69.69 (N=45)
Interfering Substances (Observed Recovery Bias)	"no clinical significance" (specific % change provided for various substances, all < 6%)
Recovery (Dilution %)	97-106% (Mean recoveries of 100%, 101%, 100%, 102% for different samples)
Analytical Range	0.01 – 100 ng/mL
Minimum Detectable Concentration	0.01 ng/mL

Study Details

Sample size used for the test set and the data provenance:
- Imprecision: Not explicitly stated as a test set, but the evaluation involved six calibrator levels and commercial controls, with 10 runs performed. Total replicates = 40. Data provenance not specified, likely internal laboratory data.
- Correlation: Forty-five (45) serum samples and ninety-eight (98) serum samples were used in two separate correlation studies. The values ranged from 0.03 to 69.69 ng/mL and 0.14 to 86.28 ng/mL, respectively. Data provenance not specified, likely internal laboratory data (e.g., from a clinical laboratory or research setting).
- Serial Monitoring: Two longitudinal patient samples were used. Data provenance not specified but are described as "serial patient monitoring studies."
- Interfering Substances: A serum pool with a cPSA concentration of about 3.7 ng/mL was used, spiked with various interfering substances.
- Recovery: Not stated as a specific test set size, but multiple dilutions were evaluated for several "samples" (at least 4 distinct samples with 5 dilutions each).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an in vitro diagnostic (IVD) assay measuring a biomarker. The "ground truth" for its performance is typically established through analytical studies comparing its measurements to a reference method (in this case, the predicate Immuno 1 cPSA Assay) and assessing its precision, linearity, and interference.
- There is no mention of "experts" in the sense of clinical reviewers or adjudicators for establishing ground truth as one would find in imaging or clinical diagnostic studies. The ground truth refers to the analyte concentration as measured by a established comparator or derived from known standards.
Adjudication method for the test set:
- Not applicable. This is an analytical performance study for an IVD assay, not a study requiring clinical adjudication of patient outcomes or interpretations. The comparison is against the predicate device's measured values.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This is an IVD assay, not an AI-powered diagnostic imaging or interpretation tool that involves human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance data presented (imprecision, correlation, interfering substances, recovery, analytical range, minimum detectable concentration) are all derived from the standalone performance of the ADVIA IMS cPSA assay. The device itself is an automated laboratory analyzer.
The type of ground truth used:
- The primary ground truth for the correlation study was the measurements obtained from the predicate device, Immuno 1 cPSA Assay. This establishes substantial equivalence.
- For imprecision, the ground truth relates to the consistency of measurements of known calibrators and controls.
- For interfering substances and recovery, the ground truth relates to expected concentrations after spiking or dilution, and the observed values are compared to these.
The sample size for the training set:
- Not applicable in the context of this 510(k) submission. This is an IVD assay, not a machine learning or AI algorithm that requires a "training set" in the traditional sense. The assay is based on established immunodiagnostic principles. Any internal development or optimization of the assay would have been done prior to this submission, but it's not described in terms of a "training set" like an AI model.
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" for an AI or machine learning model described here. This device relies on chemical and immunological reactions, with calibration performed using known standards.

Summary

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DEC 1 7 2002

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS cPSA Assay for Bayer ADVIA® Integrated Modular System (IMS)™

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

The assigned 510(k) number is: KC22288

1. Intended Use

2. Predicate Device

Product Name	Reagent Part #	Calibrator Part #
Immuno 1 cPSA Assay	T01-3982-51	T03-3983-01

3. Device / Method

Product Name	Reagent Part # / BAN Number	Calibrator Part # /BAN Number
ADVIA IMS cPSA Assay	B42-4114-42 /00955033 (100 tests)00923573 (250 tests)	B43-4115-01/06176311

Imprecision

Within-run and total imprecision were evaluated by testing six calibrator levels and commercial controls. % CV was calculated based on all replicates using one calibration curve. Ten runs were performed: two runs/day for four days, and two more runs-one run/day. Total number of replicates = 40

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ADVIA IMS		Immuno 1
Level(ng/mL)	TotalCV(%)	Level(ng/mL)	TotalCV(%)
3.47	3.0	1.0	2.5
15.55	3.4	10	2.5
77.21	3.8	50	2.1

Correlation (Y= ADVIA IMS, X=comparison system)

Correlation study was performed using forty five (45) serum samples (0.03 to 69.69 ng/mL)

Specimen type	Comparison System (X)	N	Regression Equation	Syx (ng/mL)	R	Sample Range (ng/mL)
Serum	Immuno 1	98	$0.988 * X - 0.191$	0.706	0.999	0.14-86.28
Serum	Immuno 1	45	$1.004 * X - 0.336$	0.566	0.999	0.03-69.69

Serial Monitoring

0.0 04/19/01

07/28/01

Two examples of serial patient monitoring studies using Bayer ADVIA IMS assay results in comparison to results obtained for another marketed device are shown in the following figures.

Image /page/1/Figure/6 description: The image shows two line graphs, each representing a longitudinal sample for a different patient. The first graph, titled "Longitudinal Sample - Patient 1", plots cPSA values over time from April 2001 to December 2002, with two lines representing "ADVIA IMS" and "Immuno 1". The second graph, titled "Longitudinal Sample - Patient 2", also plots cPSA values over time for a different patient, with the same two lines representing "ADVIA IMS" and "Immuno 1".

11/05/01

��ADVA IMS

Date

02/13/02

05/24/02

09/01/02

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Interfering Substances

Serum pool with cPSA concentration of about 3.7 ng/mL was spiked with hemoglobin, triglyceride, bilirubin, albumin, immunoglobulins, PAP, kallikrein, and drug pools (up to two times lethal dose) and then assayed for cPSA. In all cases the observed recovery bias was found to be of no clinical significance.

InterferingSubstance	Interfering SubstanceConcentrationmg/dL	cPSAConcentration(ng/mL)	Effect(% change)
Hemoglobin	1000	1.92	1.5
Lipids (Triglycerides)	1000	3.46	-0.5
Bilirubin	25	3.67	-1.1
IgG	6.0	2.82	-2.8
Albumin	6.5	2.86	2.0

Cross-Reactant	Cross-ReactantConcentration(µg/mL)	cPSAConcentration(ng/mL)	Effect(% change)
PAP	1.0	3.63	-0.012
Kallikrein (plasma)	1.0	3.63	-0.001
Kallikrein (urine)	1.0	2.17	-0.012
Vincristine Sulfate	13.5	2.06	-0.7
Vinblastine	5.11	2.06	-0.7
Mitomycin C	73	3.28	1.8
Tamoxifen - Free	60	2.06	-0.7
Tamoxifen - Citrate	60	2.06	-0.7
Etoposide	415	2.06	-0.7
5-Fluorouracil	1600	3.42	5.8
CyclophosphamideMonohydrate	800	3.28	1.8
Doxorubicin HCl	51.8	3.28	1.8
Diethylstibestrol	23	2.06	-0.7
Methotrexate	450	3.08	-2.6
Cis-Platinum	173	2.06	-0.7
Megestrol Acetate	243	3.22	1.8
Lupron	15

Recovery

Recovery of the cPSA dilution in the range of 0.01 to 4.0 ng/mL was evaluated. Recovery ranged from 97 to 106%.

Sample #1
Expected , ng/mL	Observed, ng/mL	Recovery, %
3.61	3.61	100
2.74	2.80	102
1.88	1.83	97
1.01	1.00	99
0.14	0.14	100
	Mean	100

Sample #2
Expected, ng/mL	Observed, ng/mL	Recovery, %
3.86	3.86	100
2.93	3.01	103
2.00	2.02	101
1.07	1.06	99
0.14	0.14	100
	Mean	101

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Sample #3
Expected , ng/mL	Observed, ng/mL	Recovery, %
4.09	4.09	100
3.07	3.06	100
2.05	2.01	98
1.03	1.03	100
0.01	0.01	100
	Mean	100
3.95	3.95	100
2.98	3.02	101
2.00	2.09	105
1.03	1.09	106
0.05	0.05	100
	Mean	102

Analytical Range

0.01 -- 100 ng/mL

Minimum Detectable Concentration

ADVIA IMS(ng/mL)	Immuno 1(ng/mL)
0.01	0.02

4. Conclusion

Performance of the ADVIA IMS cPSA Assay on a Bayer ADVIA® IMS™ is equivalent to the performance of the cPSA Assay on the predicate device (Immuno 1) and is within proposed specifications. No safety and effectiveness issues have been raised.

K. FOX

12/01/02

Date

K. Pads Director Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features an abstract design of an eagle with three lines representing its body and wings. The seal is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES · USA" in a circular arrangement.

Food and Drug Administratio 2098 Gaither Road Rockville MD 2085()

DEC 1 7 2002

Kenneth T. Edds, Ph.D. Regulatory Affairs Manager Bayer Diagnostics 511 Benedict Avenue Tarrytown, NY 10591

K022288 Re:

Trade/Device Name: cPSA (Complexed Prostate Specific Antigen) Assay for the ADVIA® IMSTM

Regulation Number: 21 CFR 866.6010

Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: LTJ; JIS Dated: December 5, 2002 Received: December 6, 2002

Dear Dr. Edds:

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 Mav 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 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 CI'R 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). Other general information on your responsibilities under the Act may be obtained 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 Sutman

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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Page

K022288 510(k) Number:

Device Name: cPSA (Complexed Prostate Specific Antigen) Assay for the ADVIA® IMS™

Indications for Use:

The Bayer ADVLA® IMS cPSA assay is an in vitro diagnostic device intended to quantitatively measure complexed prostate specific antigen (cPSA) in human serum. This assay is indicated for the measurement of serum complexed PSA as an aid in management (monitoring) of prostate cancer patients. cPSA values obtained using the Bayer ADVIA IMS assay method must be interpreted in conjunction with all other available clinical and laboratory data before a medical decision is determined.

(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)

Over-The-CounterUse

(Optional Format 1-2-96)

M. Plume des S. Bautista

ു-Off) nrucal Laboratory Devices

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.