PROSTATE SPECIFIC ANTIGEN (PSA) ASSAY FOR THE ADVIA INTEGRATED MODULAR SYSTEM

K022177 · Bayer Diagnostics Corp. · LTJ · Dec 17, 2002 · Immunology

Device Facts

• Record ID: K022177
• Device Name: PROSTATE SPECIFIC ANTIGEN (PSA) ASSAY FOR THE ADVIA INTEGRATED MODULAR SYSTEM
• Applicant: Bayer Diagnostics 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 PSA assay is an in vitro diagnostic device intended to quantitatively measure prostate specific antigen (PSA) in human serum. This assay is indicated for the measurement of serum PSA as an aid in management (monitoring) of prostate cancer patients. 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 PSA assay is an in vitro diagnostic test for the quantitative measurement of prostate-specific antigen (PSA) in human serum. It is designed for use on the Bayer ADVIA Integrated Modular System (IMS). The device processes serum samples to provide PSA concentration values, which clinicians use as an aid in monitoring prostate cancer patients. Results must be interpreted alongside other clinical and laboratory data. The assay is intended for professional use in a clinical laboratory setting.

Clinical Evidence

Bench testing only. Imprecision was evaluated using six calibrator levels and commercial controls, showing total CVs between 1.7% and 2.7%. Correlation studies with 44-54 serum samples against the predicate (Immuno 1) yielded a correlation coefficient (R) of 0.999 and a regression equation of Y = 0.97X - 0.06. Analytical range is 0.01–100 ng/mL. Interference testing with hemoglobin, lipids, bilirubin, albumin, immunoglobulins, and various drugs showed no clinically significant recovery bias. Recovery studies ranged from 97% to 104%.

Technological Characteristics

In vitro diagnostic immunoassay for use on the Bayer ADVIA IMS platform. Analytical range: 0.01–100 ng/mL. Minimum detectable concentration: 0.01 ng/mL. The system utilizes automated reagent and calibrator handling. No specific software algorithm architecture or material specifications provided.

Indications for Use

Indicated for the quantitative measurement of serum PSA as an aid in the management (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 PSA Assay (K013488)

Submission Summary (Full Text)

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DEC 1 7 2002

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

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.

X 02217 The assigned 510(k) number is:

# 1. Intended Use

The Bayer ADVIA® IMS PSA assay is an in vitro diagnostic device intended to quantitatively measure prostate specific antigen (PSA) in human serum. This assay is indicated for the measurement of serum PSA as an aid in management (monitoring) of prostate cancer patients. 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.

# 2. Predicate Device

| Product Name | Reagent Part # | Calibrator Part # |
|--------------------|----------------|-------------------|
| Immuno 1 PSA Assay | T01-3450-51 | T03-3541-01 |

# 3. Device / Method

| Product Name | Reagent Part # / BAN<br>Number | Calibrator Part # /<br>BAN Number |
|---------------------|---------------------------------------------------------------|-----------------------------------|
| ADVIA IMS PSA Assay | B42-3912-42 /<br>02598475 (100 tests)<br>06694045 (250 tests) | B43-3940-01/<br>03625840 |

### 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.

| ADVIA IMS | | Immuno 1 | |
|---------------|-------------|---------------|-------------|
| Level (ng/mL) | Total CV(%) | Level (ng/mL) | Total CV(%) |
| 2.6 | 2.7 | 3 | 3.1 |
| 6.5 | 1.8 | 23 | 3.4 |
| 24.1 | 1.7 | 96 | 2.5 |
| 99.1 | 2.0 | | |

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

Correlation study was performed with forty four (44) serum samples (0.07 to 62.93 ng/mL).

| Specimen type | Comparison System (X) | N | Regression Equation | Syx (ng/mL) | R | Sample Range (ng/mL) |
|--------------------------|-----------------------|-------|---------------------|-------------|-------|----------------------|
| Serum | Immuno 1 | 54 | $0.97 * X - 0.18$ | 0.93 | 0.999 | 0.37-79.70 |
| Serum | Immuno 1 | 44 | $0.97 * X - 0.06$ | 0.78 | 0.999 | 0.07-62.93 |
| 95% Confidence Intervals | | | | | | |
| | | µg/L | Ng/mL | µg/L | ng/mL | |
| Slope | | 0.951 | 0.951 | 0.981 | 0.981 | |
| Intercept | | -0.49 | -0.49 | 0.37 | 0.37 | |
| Sy.x | | 0.53 | 0.53 | 1.27 | 1.27 | |

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### Serial Monitoring

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/2 description: The image shows two line graphs comparing PSA levels over time for two patients. The first graph, titled "Longitudinal Sample - Patient 1", plots PSA levels from approximately 50 to 90 between July 2001 and December 2002. The second graph, titled "Longitudinal Sample - Patient 2", plots PSA levels from approximately 10 to 80 between July 2001 and September 2002. Both graphs compare "ADVIA IMS" and "Immuno 1" measurements.

### Interfering Substances

Serum pool with PSA concentration of 4.0 ng/mL was spiked with hemoglobin, triglyceride, billirubin, albumin, immunoglobulins, PAP, kallikrein, and drug pools (up to two times lethal dose) and then assayed for PSA. In all cases the observed recovery bias was found to be of no clinical significance.

| Interfering<br>Substance | Interfering Substance<br>Concentration | | Analyte<br>Concentration | | Effect |
|---------------------------|----------------------------------------|---------|--------------------------|---------|------------------|
| | SI Units | (mg/dL) | (µg/L) | (ng/mL) | (%) |
| Hemoglobin | 10.0 g/L | 1000 | 2.08 | 2.08 | 2.8 |
| Lipids<br>(Triglycerides) | 11.3 mmol/L | 1000 | 3.57 | 3.57 | 0.1 |
| Bilirubin | 428 µmol/L | 25 | 4.05 | 4.05 | 0.7 |
| Immunoglobulin (IgG) | 60.0 g/L | 6000 | 3.13 | 3.13 | -5.3 |
| Albumin | 65.0 g/L | 6500 | 3.05 | 3.05 | -1.3 |
| Cross-Reactivities | | | | | |
| Cross-Reactant | Cross-Reactant<br>Concentration | | Analyte<br>Concentration | | Cross-Reactivity |
| | (µg/mL) | | (µg/L) | (ng/mL) | (%) |
| PAP | 1.0 | | 3.99 | 3.99 | 0.015 |
| Kallikrein (plasma) | 1.0 | | 4.23 | 4.23 | 0.018 |
| Kallikrin (urine) | 1.0 | | 3.86 | 3.86 | 0.013 |
| Vincristine Sulfate | 13.5 | | 3.82 | 3.82 | 0.3 |
| Vinblastine | 5.11 | | 3.82 | 3.82 | 0.3 |
| Mitomycin C | 73 | | 3.86 | 3.86 | 1.2 |
| Tamoxifen - Free | 60 | | 3.82 | 3.82 | 0.3 |
| Tamoxifen - Citrate | 60 | | 3.82 | 3.82 | 0.3 |

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| 5-Fluorouracil | 1600 | 3.65 | 3.65 | -1.8 |
|---------------------------------|------|------|------|------|
| Cyclophosphamide<br>Monohydrate | 800 | 3.86 | 3.86 | 1.2 |
| Doxorubicin HCl | 51.8 | 3.86 | 3.86 | 1.2 |
| Diethylstibestrol | 23 | 3.82 | 3.82 | 0.3 |
| Methotrexate | 450 | 3.67 | 3.67 | -0.9 |
| Cis-Platinum | 173 | 3.82 | 3.82 | 0.3 |
| Lupron | 15 | 3.59 | 3.59 | 2.4 |
| Megestrol Acetate | 243 | 3.86 | 3.86 | 1.2 |

## Recovery

Recovery of the PSA dilution in the range of 0.01 to 4.0 ng/mL was evaluated. Recovery ranged from 97 to 104%.

| Sample #1 | | |
|------------------|-----------------|-------------|
| Expected , ng/mL | Observed, ng/mL | Recovery, % |
| 4.31 | 4.31 | 100 |
| 3.28 | 3.17 | 97 |
| 2.26 | 2.23 | 99 |
| 1.23 | 1.21 | 99 |
| 0.20 | 0.20 | 100 |
| | Mean | 99 |
| Sample #2 | | |
| Expected , ng/mL | Observed, ng/mL | Recovery, % |
| 4.27 | 4.27 | 100 |
| 3.25 | 3.35 | 103 |
| 2.23 | 2.24 | 100 |
| 1.21 | 1.21 | 100 |
| 0.19 | 0.19 | 100 |
| | Mean | 101 |
| Sample #3 | | |
| Expected , ng/mL | Observed, ng/mL | Recovery, % |
| 4.58 | 4.58 | 100 |
| 3.44 | 3.41 | 99 |
| 2.30 | 2.28 | 99 |
| 1.16 | 1.19 | 103 |
| 0.02 | 0.02 | 100 |
| | Mean | 100 |

| Sample # 4 | | |
|-----------------|-----------------|-------------|
| Expected, ng/mL | Observed, ng/mL | Recovery, % |
| 4.38 | 4.38 | 100 |
| 3.30 | 3.25 | 98 |
| 2.22 | 2.24 | 101 |
| 1.14 | 1.19 | 104 |
| 0.06 | 0.06 | 100 |
| | Mean | 101 |

# Analytical Range
0.01 – 100 ng/mL

0.01-100 ng/ml

# Minimum Detectable Concentration

| ADVIA IMS<br>(ng/mL) | Immuno 1<br>(ng/mL) |
|----------------------|---------------------|
| 0.01 | 0.03 |

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# 4. Conclusion

Performance of the ADVIA IMS PSA Assay on a Bayer ADVIA® IMS™ is equivalent to the specifications. No safety and effectiveness issues have been raised

12/04/02

Date

י

K. Edds 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 logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of three human profiles facing right, arranged in a stacked formation. The profiles are rendered in black and have a flowing, abstract design. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the left side of the profile graphic.

Food and Drug Administration 2098 Gaither Road Rockville MD_20850

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

Re:

k022177. Trade/Device Name: PSA (Prostate Specific Antigen) Assay for the ADVIA® IMS™ 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 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 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 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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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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### Kozal 77 510(k) Number:

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

# Indications for Use:

The Bayer ADVIA® IMS PSA assay is an in vitro diagnostic device intended to quantitatively measure prostate specific antigen (PSA) in human serum. This assay is indicated for the measurement of serum PSA as an aid in management (monitoring) of prostate cancer patients. PSA values obtained using the Baver 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

(Optional Format 1-2-96)

Hecord for H. Bantista

(Division Sion-Off) Division of Chrical Laboratory Device 510jk) Number --