COMPLEXED PROSTATE SPECIFIC ANTIGEN (CPSA) ASSAY FOR THE BAYER ADVIA INTEGRATED MODULE SYSTEM

K022288 · Bayer Corp. · LTJ · Dec 17, 2002 · Immunology

Device Facts

• Record ID: K022288
• Device Name: COMPLEXED PROSTATE SPECIFIC ANTIGEN (CPSA) ASSAY FOR THE BAYER ADVIA INTEGRATED MODULE SYSTEM
• Applicant: Bayer Corp.
• Product Code: LTJ · Immunology
• Decision Date: Dec 17, 2002
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

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 Story

The Bayer ADVIA IMS cPSA assay is an in vitro diagnostic test for human serum. It utilizes a monoclonal antibody capture method to isolate PSA complexed with alpha-1-antichymotrypsin (ACT). A second, unlabeled monoclonal antibody specific for free PSA is included to block free PSA binding, ensuring the assay measures only complexed PSA. The device is intended for use in clinical laboratory settings by trained personnel. Results are provided to healthcare providers to assist in monitoring prostate cancer progression or response to therapy. Clinical decisions must be made in conjunction with other laboratory and clinical data. The assay provides a quantitative value (ng/mL) which helps clinicians track disease status over time.

Clinical Evidence

Bench testing only. Performance was evaluated through imprecision studies (total CV 3.0-3.8%), analytical range (0.01-100 ng/mL), and recovery (97-106%). Correlation with the predicate device was established using 98 serum samples (R=0.999, slope 0.988). Interference testing showed no clinically significant bias from hemoglobin, lipids, bilirubin, or various chemotherapeutic drugs. Serial monitoring was demonstrated via longitudinal patient case studies.

Technological Characteristics

In vitro diagnostic immunoassay using monoclonal antibody capture. Employs a dual-antibody system: one capture antibody for total PSA and a second unlabeled antibody to block free PSA, isolating cPSA. Analytical range: 0.01-100 ng/mL. Platform: Bayer ADVIA IMS. Connectivity: Integrated modular system. Sterilization: Not applicable (reagent kit).

Indications for Use

Indicated for the quantitative measurement of serum complexed prostate specific antigen (cPSA) to aid in the management and monitoring of prostate cancer patients.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• Immuno 1 cPSA Assay (T01-3982-51)

Submission Summary (Full Text)

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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

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.

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.

#### 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 # /<br>BAN Number |
|----------------------|---------------------------------------------------------------|-----------------------------------|
| ADVIA IMS cPSA Assay | B42-4114-42 /<br>00955033 (100 tests)<br>00923573 (250 tests) | B43-4115-01/<br>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<br>(ng/mL) | Total<br>CV(%) | Level<br>(ng/mL) | Total<br>CV(%) |
| 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

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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.

| Interfering<br>Substance | Interfering Substance<br>Concentration<br>mg/dL | cPSA<br>Concentration<br>(ng/mL) | Effect<br>(% 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-Reactant<br>Concentration<br>(µg/mL) | cPSA<br>Concentration<br>(ng/mL) | Effect<br>(% 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 |
| Cyclophosphamide<br>Monohydrate | 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<br>(ng/mL) | Immuno 1<br>(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 [phone]. 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 [phone] or [phone] 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)

OR

Over-The-CounterUse

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