QUALISYS PSA IMMUNOASSAY

K990234 · Qualisys Diagnostics, Inc. · LTJ · Jul 8, 1999 · Immunology

Device Facts

• Record ID: K990234
• Device Name: QUALISYS PSA IMMUNOASSAY
• Applicant: Qualisys Diagnostics, Inc.
• Product Code: LTJ · Immunology
• Decision Date: Jul 8, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

The Qualisys PSA Immunoassay is a paramagnetic particle immunoassay for the in vitro quantitative determination of prostate-specific antigen (PSA) in human serum. The Qualisys PSA Immunoassay is further indicated for the serial measurement of PSA as an aid in the prognosis and management of patients with prostate cancer.

Device Story

Qualisys PSA Immunoassay is a two-site chemiluminescence sandwich immunoassay for quantitative PSA measurement in human serum. Process: 100 µL sample/calibrator incubated with PSA antibody; streptavidin-coated paramagnetic particles added to bind sandwich complex; unbound materials washed away; chemiluminogenic substrate added; light emission measured by Zylux luminometer (photomultiplier). Output: Relative Light Units (RLU) proportional to PSA concentration. Used in clinical laboratories; operated by technicians. Data analysis performed via external software using cubic spline curve fitting. Assists clinicians in monitoring prostate cancer patients.

Clinical Evidence

Bench testing only. Method comparison study (n=108) against Abbott IMx® PSA showed correlation (y = 0.9955x + 0.5185, r^2 = 0.9747). Precision: Intra-assay CVs 1.7-3.4%, Inter-assay CVs 2.6-5.7%. Analytical sensitivity 0.003 ng/mL; functional sensitivity 0.1 ng/mL. Spike recovery 90-110%; dilution recovery 92-108%. No high dose hook effect up to 1250 ng/mL. Interference testing performed for bilirubin, hemoglobin, IgG, PAP, protein, triglycerides, and various drugs.

Technological Characteristics

Two-site sandwich immunoassay; chemiluminescence detection via photomultiplier tube. Solid-phase: streptavidin-coated paramagnetic particles. Label: Alkaline Phosphatase. Substrate: ImmuGlow™ (Indoxyl-3-phosphate and lucigenin). Instrument: Zylux luminometer. Data analysis: external software using cubic spline curve fitting. Manual processing. Storage: 2-8 °C.

Indications for Use

Indicated for in vitro quantitative determination of PSA in human serum and serial measurement of PSA to aid in prognosis and management of patients with prostate cancer.

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

• Abbott IMx® PSA (P910007)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows a sequence of handwritten alphanumeric characters. The sequence starts with the letter 'K', followed by the numbers '990234'. The characters are written in a simple, slightly irregular style.

Image /page/0/Picture/2 description: The image shows the logo for Qualisys Diagnostics, Inc. The word "Qualisys" is in a large, bold font, with the "Q" being particularly large and stylized. Below "Qualisys" is the text "Diagnostics, Inc." in a smaller font. The logo is simple and professional.

## 510(k) Summary

### Qualisys PSA Immunoassay

This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

| 1. | Submitter<br>name, address,<br>contact | Qualisys Diagnostics, Incorporated<br>16 Technology Drive, Suite 118<br>Irvine, CA 92618 |
|----|----------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | | Telephone: [phone]<br>Fax: [phone] |
| | | Contact Person: Grace Kwan |
| | | Date Prepared: May 19, 1999 |
| 2. | Device name | Proprietary name: Qualisys PSA Immunoassay |
| | | Common name: Chemiluminescense assay for the determination of<br>Prostate-Specific Antigen (PSA). |
| | | Classification Name: Prostate-Specific Antigen (PSA) for Management<br>of Prostate Cancers |
| 3. | Predicate<br>device | Abbott IMx® PSA<br>(P910007) |
| 4. | Device<br>description | The Qualisys PSA Immunoassay is a two-site chemiluminescense assay. 1st incubation: 15 minutes at room temperature. Specimen, control or calibrator [100 µL] and PSA Antibody Solution [100 µL] react to form a sandwich complex. 2nd incubation: 2 minutes at room temperature. Streptavidin-coated paramagnetic particle solution [25 µL] is added to the reaction mixture. After the 2-minute incubation, the sandwich complex is bound to the solid-phase via the interaction of biotin and streptavidin. Removal of unbound materials: The paramagnetic particles are washed four times with wash buffer [1.0 mL/wash] to remove unbound materials. |
| | | 16 Technology Drive, Suite 118 • Irvine, CA 92618<br>[phone] • Fax [phone]<br>Attachment 1<br>Page 1 of 4 |

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#### Qualisys Diagnostics, Incorporated

| | Device<br>description<br>(continued) | Re-suspension of paramagnetic particles: Deionized (DI) water [25<br>uL] is added to re-suspend the washed paramagnetic particles. | | | |
|----|--------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|
| | | | Substrate addition and detection: Chemiluminogenic substrate [50 uL]<br>is added to the solid-phase bound complex and results in "glow"<br>chemiluminescence, which is measured using a luminometer<br>(photomultiplier). Emission of light is quantified for 1 second, and is<br>expressed in relative light units (RLU). | | |
| | | The amount of bound labeled antibody in RLU's is directly<br>proportional to the concentration of PSA in the sample. Results are<br>determined using cubic spline immunoassay curve fitting. | | | |
| 5. | Intended use | The Qualisys PSA Immunoassay is a paramagnetic particle immunoassay<br>intended for the in vitro quantitative determination of prostate-specific<br>antigen (PSA) in human serum. The Qualisys PSA Immunoassay is<br>further indicated for the serial measurement of PSA as an aid in the<br>prognosis and management of patients with prostate cancer. | | | |
| 6. | Comparison to<br>predicate<br>device | The Qualisys PSA Immunoassay is substantially equivalent to other<br>products in commercial distribution intended for similar use. Most notably<br>it is substantially equivalent to the currently marketed Abbott IMx® PSA.<br>The following tables compare the Qualisys PSA Immunoassay with the<br>predicate device, Abbott IMx® PSA: | | | |
| | | | | | |
| | | Similarities: | | | |
| | | Assay Methodology:<br>● | Sandwich immunoassay | | |
| | | Sample Type: | Serum | | |
| | | Storage Condition: | 2-8 °C | | |
| | | I abel | Alkaline Phosphatase | | |

- Photomultiplier Tube (PMT) Detector: .

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#### Qualisys Diagnostics, Incorporated

## 510(k) Summary (continued)

| Comparison to | Differences: | | |
|-----------------------------------------------------|-----------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| predicate<br>(continued) | Feature | Qualisys PSA | Abbott IMx® PSA |
| | Intended Use | For the in vitro<br>quantitative determination<br>of PSA in human serum.<br>It is further indicated for<br>the serial measurement of<br>PSA as an aid in the<br>prognosis and<br>management of patients<br>with prostate cancer. | For the quantitative<br>measurement of PSA in<br>human serum: 1) as an<br>aid in the detection of<br>prostate cancer when<br>used in conjunction with<br>DRE in men aged 50<br>years or older. Prostatic<br>biopsy is required for<br>diagnosis of cancer; 2) as<br>an adjunctive test used as<br>an aid in the management<br>of prostate cancer<br>patients. |
| | Sample Volume | 100 µL | 150 µL |
| | Assay Range | 0 to 50 ng/mL | 0 to 100 ng/mL |
| | Temp. Control | Not Required<br>(Room Temperature) | Required |
| | Instrument<br>Required | Zylux Luminometer | Abbott IMx® Analyzer |
| | Test Processing | Manual<br>(A liquid handling system<br>may be use to assist in the<br>pipetting of multiple<br>samples.) | Automated |
| | Control Levels | 2 | 3 |
| | Calibration<br>Levels | 5 | 6 |
| | Capture<br>Antibody | Monoclonal | Polyclonal |
| | Solid-phase | Streptavidin-coated<br>paramagnetic particles | Monoclonal Anti-PSA<br>coated microparticles |
| | Substrate | ImmuGlow™ (Indoxyl -3-<br>phosphate and lucigenin) | 4-Methylumbelliferyl<br>Phosphate |
| | Detection | Chemiluminescence | Fluorescence |
| | Data Analysis | External software: cubic<br>spline for curve fitting and<br>data reduction | Internal data reduction<br>via microcomputer |
| | Calibration | Full calibration curve with<br>every run | Full calibration curve<br>every 4 weeks |
| Comparison to<br>predicate<br>device<br>(continued) | Performance Characteristics:<br>Feature | Qualisys PSA<br>ng/mL PSA | Abbott IMx® PSA<br>ng/mL PSA |
| | Precision<br>Intra-assay | Low (0.52) 3.4%<br>Med (3.05) 1.7%<br>High (23.06) 3.0% | Low (4.6) 3.5%<br>Med (15.6) 3.3%<br>High (60.2) 3.1% |
| | Inter-assay | Low (0.52) 5.7%<br>Med (3.05) 2.6%<br>High (23.06) 3.7% | Low (4.6) 4.7%<br>Med (15.6) 4.5%<br>High (60.2) 5.3% |
| | Analytical<br>Sensitivity | 0.003 ng PSA/mL | 0.1 ng PSA/mL |
| | Functional<br>Sensitivity | 0.1 ng PSA/mL | Not reported |
| | Spike Recovery | 90 to 110% | 91 to 103% |
| | Dilution<br>Recovery | 92 to 108% | Not reported |
| | Method<br>Comparison | versus Abbott IMx® PSA:<br>n = 108<br>Range of values (Abbott): 0 to 46.83 ng PSA/mL<br>Range of values (Qualisys): 0 to 42.30 ng PSA/mL<br>$y = 0.9955x + 0.5185 (Least Squares)$<br>$r^2$ = 0.9747<br>$S^2_{slope}$ = 0.000243<br>$S^2_{y-intercept}$ = 0.067012 | |
| | Interfering<br>Substances | No interference up to:<br>Bilirubin 49 mg/dL<br>Hemoglobin 600 mg/dL<br>IgG 1900 mg/dL<br>PAP 1000 ng/mL<br>Protein 13 g/dL<br>Triglycerides 2730 mg/dL<br>Cyclophosphamide 700 µg/mL<br>DES 2 µg/mL<br>Doxorubicin HCI 16 µg/mL<br>Methotrexate 30 µg/mL<br>Megestrol Acetate 90 µg/mL<br>Flutamide 10 µg/mL<br>Lupron 100µg/mL | No interference up to:<br>25 mg/dL<br>600 mg/dL<br>250-2900 mg/dL<br>1000 ng/mL<br>3-13 g/dL<br>3000 mg/dL<br>700 µg/mL<br>2 µg/mL<br>16 µg/mL<br>30 µg/mL<br>90 µg/mL<br>10 µg/mL<br>100µg/mL |
| | High Dose Hook<br>Effect | No high dose hook effect<br>up to 1250 ng/mL | Not reported |

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle with three curved lines representing its wings.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL - 9 1999

Ms. Grace Kwan Director, Ouality and Regulatory Affairs Qualisys Diagnostics, Inc. 16 Technology Drive, Suite 118 Irvine, California 92618

Re: K990234

> Trade Name: Oualisys PSA Immunoassay Regulatory Class: II Product Code: LTJ Dated: May 19, 1999 Received: May 20, 1999

Dear Ms. Kwan:

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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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 [phone].

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"(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 [phone] or [phone], or at its internet address "http://www.fda.gov/cdrlv/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

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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### Attachment 4

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# Indications for Use Statement

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

| 510(k) Number | K990234 |
|---------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Device Name | Qualisys PSA Immunoassay |
| Indications for Use | The Qualisys PSA Immunoassay is a paramagnetic particle immunoassay for the <i>in vitro</i> quantitative determination of prostate-specific antigen (PSA) in human serum. The Qualisys PSA Immunoassay is further indicated for the serial measurement of PSA as an aid in the prognosis and management of patients with prostate cancer. |

#### PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IS NEEDED ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Concurrence of CDRH, Office of Device Evaluation (ODE)

| (Division Sign-Off) | |
|-----------------------------------------|---------|
| Division of Clinical Laboratory Devices | |
| 510(k) Number | K990234 |

| Prescription Use<br>(Per 21 CFR 801.109) | <div>✓</div> | OR | Over-The-Counter Use | |
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