AFP ASSAY FOR THE ADVIA INTEGRATED MODULAR SYSTEM

K020807 · Bayer Diagnostics Corp. · LOJ · Oct 1, 2002 · Immunology

Device Facts

• Record ID: K020807
• Device Name: AFP ASSAY FOR THE ADVIA INTEGRATED MODULAR SYSTEM
• Applicant: Bayer Diagnostics Corp.
• Product Code: LOJ · Immunology
• Decision Date: Oct 1, 2002
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

The Bayer ADVIA® IMS™ AFP assay is an in vitro diagnostic device intended to quantitatively measure afetoprotein (AFP) in human serum on the Bayer ADVIA IMS system as an aid in the management of nonseminomatous testicular cancer. AFP 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. AFP testing is not recommended as a screening procedure to detect cancer in the general population.

Device Story

In vitro diagnostic assay for quantitative measurement of alpha-fetoprotein (AFP) in human serum; performed on Bayer ADVIA IMS system. Used in clinical laboratory settings by trained personnel. Input: human serum sample. Principle: immunoassay. Output: numerical AFP concentration (ng/mL). Healthcare providers use results alongside clinical/laboratory data to manage nonseminomatous testicular cancer patients; serial monitoring helps track disease progression or response to therapy. Does not screen general population.

Clinical Evidence

Bench testing only. Performance evaluated via imprecision studies (Total CV 2.3-2.7%), analytical range (0.08-400 ng/mL), and method correlation against predicate (N=50, Y=1.06X-3.18, R=0.998). Interference testing performed for hemoglobin, lipids, bilirubin, IgG, and albumin. Reference range established using 250 healthy subjects. Serial monitoring data provided for clinical context.

Technological Characteristics

In vitro diagnostic immunoassay. Analyte: alpha-fetoprotein. Analytical range: 0.08-400 ng/mL. System: Bayer ADVIA IMS. Reagents and calibrators provided as specific part numbers. No specific materials or software architecture details provided.

Indications for Use

Indicated for quantitative measurement of AFP in human serum as an aid in the management of nonseminomatous testicular cancer. Not for use as a general population cancer screening procedure.

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 AFP Assay

Submission Summary (Full Text)

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# OCT 01 2002

# 510(k) SUMMARY OF SAFETY AND EFFECTIVENESS AFP 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:

## 1. Intended Use

The Bayer ADVIA® IMS™ AFP assay is an in vitro diagnostic device intended to quantitatively measure afetoprotein (AFP) in human serum on the Bayer ADVIA IMS system as an aid in the management of nonseminomatous testicular cancer. AFP 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. AFP testing is not recommended as a screening procedure to detect cancer in the general population.

## 2. Predicate Device

| Product Name | Reagent Part # | Calibrator Part # |
|--------------------|----------------|-------------------|
| Immuno 1 AFP Assay | T01-3100-51 | T03-3187-01 |

## 3. Device / Method

| Product Name | Reagent Part # / BAN<br>Number | Calibrator Part # /<br>BAN Number |
|---------------------|--------------------------------|-----------------------------------|
| ADVIA IMS AFP Assay | B42-3890-23 / | B43-3923-01 / |
| | 09750523 (100 tests) | 09022137 |
| | 01440029 (250 tests) | |

## Imprecision

| ADVIA IMS | | Immuno 1 | |
|------------------|----------------|------------------|----------------|
| Level<br>(ng/mL) | Total<br>CV(%) | Level<br>(ng/mL) | Total<br>CV(%) |
| 4.6 | 2.3 | 20 | 2.1 |
| 18.97 | 2.7 | 50 | 2.2 |
| 93.52 | 2.6 | 200 | 3.6 |

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

| Specimen type | Comparison System (X) | N | Regression Equation | Syx (ng/mL) | R | Sample Range (ng/mL) |
|---------------|-----------------------|----|---------------------|-------------|-------|----------------------|
| Serum | Immuno 1 | 50 | Y=1.06 * X -3.18 | 5.82 | 0.998 | 0.71 - 338.92 |

### Interfering Substances

| Interfering<br>Substance | Interfering Substance<br>Concentration<br>mg/dL | AFP<br>Concentration<br>(ng/mL) | Effect<br>(% change) |
|--------------------------|-------------------------------------------------|---------------------------------|----------------------|
| Hemoglobin | 1000 | 10.2 | 5.6 |
| Lipids (Triglycerides) | 1000 | 19.8 | 7.5 |
| Bilirubin | 25 | 21.3 | -4.5 |
| IgG | 6.0 | 16.4 | 8.3 |
| Albumin | 6.5 | 14.8 | 4.8 |

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#### Expected values'

As with all tests, each laboratory should establish its own reference range. In a group of 250 healthy people, 97.5% of the serum AFP values were found to be 0.8 ng/mL (0.66 IU/mL) to 8.9 ng/mL (7.35 IU/mL). The distribution of the AFP values for these 250 patient samples is shown in Figure 1. Substantially higher values are often found when malignant disease is present, particularly in patients with nonseminomatous turnors. However, low AFP values do not rule out the presence of malignant disease.

Image /page/1/Figure/2 description: The image is a bar graph showing the frequency of AFP values in ng/mL. The x-axis represents the AFP values, ranging from 1 to >11, while the y-axis represents the frequency, ranging from 0 to 100. The bar for AFP value 3 has the highest frequency, reaching approximately 93, while the bar for AFP value 2 has a frequency of approximately 65.

### DISTRIBUTION OF SERUM AFP ASSAY VALUES

| PATIENT<br>POPULATION | N | AFP ASSAY VALUES (ng/mL) | | | | MEDIAN |
|--------------------------------------------|-----|--------------------------|-------------------|-----------------|-------------|--------|
| | | 0 - 8.9<br>(%) | >8.9 - 100<br>(%) | >100-400<br>(%) | >400<br>(%) | |
| Healthy Subjects | 350 | 98.3 | 1.7 | 0.0 | 0.0 | 2.5 |
| Testicular Cancer<br>nonseminomatous | 100 | 36.0 | 40.0 | 14.0 | 10.0 | 20.2 |
| Testicular Cancer<br>mixed germ cell tumor | 46 | 43.5 | 45.7 | 6.5 | 4.3 | 11.6 |
| Testicular Cancer<br>seminomatous | 8 | 75.0 | 25.0 | 0.0 | 0.0 | 2.5 |
| Prostate Cancer /<br>Bladder Cancer | 40 | 97.5 | 2.5 | 0.0 | 0.0 | 3.4 |
| Lung Cancer | 29 | 96.6 | 0.0 | 0.0 | 3.4 | 3.8 |
| Colorectal Cancer | 38 | 89.5 | 10.5 | 0.0 | 0.0 | 4.5 |
| Liver Cancer | 67 | 0.0 | 31.3 | 20.9 | 47.8 | 310.9 |
| Breast Cancer | 10 | 80.0 | 20.0 | 0.0 | 0.0 | 4.8 |
| Cirrhosis | 50 | 88.0 | 12.0 | 0.0 | 0.0 | 4.0 |
| Hepatatis | 50 | 88.0 | 12.0 | 0.0 | 0.0 | 3.9 |
| Benign Genito-urinary<br>disease | 29 | 93.1 | 6.9 | 0.0 | 0.0 | 3.1 |
| Other nonmalignant | 37 | 100.0 | 0.0 | 0.0 | 0.0 | 2.3 |

' Immuno 1 data on file

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#### Monitoring data

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/2/Figure/2 description: The image contains two line graphs that compare AFP levels over time between ADVIA IMS and a marketed device. The left graph shows a significant increase in AFP levels around 12/10/01, reaching a peak of approximately 160-180 ng/mL by 02/03/02. The right graph shows a smaller increase in AFP levels around 11/05/01, reaching a peak of approximately 60-70 ng/mL. Both graphs show a decline in AFP levels towards the end of the plotted time period.

# Analytical Range

0.08 - 400 ng/mL

#### Minimum Detectable Concentration

| ADVIA IMS<br>(ng/mL) | Immuno 1<br>(ng/mL) |
|----------------------|---------------------|
| 0.08 | 0.1 |

## 4. Conclusion

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

Kenneth T. Edds Director Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097 Date

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around a symbol. The symbol is a stylized representation of three human profiles facing right, with flowing lines beneath them. The profiles are meant to represent the department's focus on people and their well-being.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Kenneth T. Edds, Ph.D. Regulatory Affairs Baver Corporation 511 Benedict Avenue Tarrytown, NY 10591-5097

OCT 01 2002

Re: k020807

> Trade/Device Name: AFP (α-Fetoprotein) 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: LOJ Dated: August 29, 2002 Received: September 3, 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. Ilsting 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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## Page 2 -

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 [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/cdrl/dsmaldsmamain.html".

Sincerely yours,

Steven Sutman

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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#### K020807 510(k) Number:

Device Name: AFP (α-Fetoprotein) Assay for the ADVIA® IMS™

## Indications for Use:

The Bayer ADVIA® IMS™AFP assay is an in vitro diagnostic device intended to quantitatively measure orfetoprotein (AFP) in human serum on the Bayer ADVIA IMS system as an aid in the management of nonseminomatous testicular cancer. AFP 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. AFP testing is not recommended as a screening procedure to detect cancer in the general population.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Deborah M. Moore

(Division Sign-O Division of Clinical Labor 510jk) Number _

Prescription Use (Per 21 CFR 801.109)

OR

Over-The-CounterUse

(Optional Format 1-2-96)