ADVANTAGE CHEMILUMINESCENCE PROSTATE SPECIFIC ANTIGEN (PSA) IMMUNOASSAY

K980716 · Nichols Institute Diagnostics · LTJ · Apr 3, 1998 · Immunology

Device Facts

• Record ID: K980716
• Device Name: ADVANTAGE CHEMILUMINESCENCE PROSTATE SPECIFIC ANTIGEN (PSA) IMMUNOASSAY
• Applicant: Nichols Institute Diagnostics
• Product Code: LTJ · Immunology
• Decision Date: Apr 3, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

Intended for use with the Nichols Advantage Specialty System for the quantitative determination of prostate specific antigen (PSA) in human serum and is to be used as an adjunct in the management of patients with prostate cancer.

Device Story

Nichols Advantage PSA is a two-site chemiluminescence sandwich immunoassay. Input: 20uL human serum sample. Process: Sample reacts with biotinylated monoclonal PSA-specific antibody and acridinium-labeled rabbit antibody; complex binds to streptavidin-coated magnetic particles. System automatically washes particles and injects Trigger 1 (hydrogen peroxide/acid) and Trigger 2 (sodium hydroxide) to oxidize acridinium ester, emitting light. Output: Light emission quantified in relative light units (RLU) by integrated system luminometer; concentration determined via instrument-specific calibration curve. Used in clinical laboratory settings by trained personnel. Output assists clinicians in managing prostate cancer patients by providing quantitative PSA levels.

Clinical Evidence

Bench testing only. Method comparison study (n=183 split samples) against predicate showed linear regression y = 0.974x + 0.25 (R=0.885). Sensitivity is 0.1 ng/mL. Precision studies (intra-assay %CV 2.3-6.1%; inter-assay %CV 3.6-9.8%). No high-dose hook effect up to 5,000 ng/mL. Interference testing performed for hemoglobin, bilirubin, lipemia, and PAP.

Technological Characteristics

Two-site chemiluminescence sandwich immunoassay. Uses biotinylated monoclonal antibodies and acridinium-labeled rabbit antibodies. Solid phase: streptavidin-coated magnetic particles. Detection: luminometer measuring RLU. Energy source: electrical (system-integrated). Connectivity: reagent bar codes for master curve input. Calibration: 2-point calibration every 4 hours.

Indications for Use

Indicated for the quantitative determination of prostate specific antigen (PSA) in human serum as an adjunct in the 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

• Hybritech Tandem®-R PSA

Submission Summary (Full Text)

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### 510(k) SUMMARY

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

#### K965031 1780716 510(k) Number:

APR - 3 1998

1. Name of Submitter, Contact Person and Date Summary prepared:

Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, California 92675 Phone: [phone] Fax: [phone]

Contact Person: Jimmy Wong Date Prepared: January 5, 1998

- 2. Device Name:

| Trade/Proprietary Name: | Nichols Advantage™ Chemiluminescence Prostate Specific Antigen Assay |
|-------------------------|-----------------------------------------------------------------------------------|
| Common/Usual Name: | Chemiluminescence assay for the determination of prostate-specific antigen (PSA). |
| Classification Name: | System, Test, Prostate Specific Antigen |

#### 3. Predicate Device:

We claim substantial equivalence to the Hybritech Tandem®-R PSA

#### 4. Device Description:

The Nichols Advantage™ PSA is a two-site chemiluminescence assay. Total duration of assay is 30 minutes at 37ºC.

18 Incubation: 20 minutes at 37℃. Sample or control or calibrator (20uL), biotinylated monoclonal PSA specific antibody (80uL), and acridinium labeled rabbit specific antibody (50uL) react to form a sandwich complex.

2nd Incubation: 10 minutes at 37℃. Assay buffer (50uL) and streptavidin coated magnetic particles (25uL) are added to the reaction mixture. After the 10 minute incubation, the sandwich complex is bound to the solid phase via the interaction of biotin and streptavidin.

The reaction mixture is aspirated from the reaction well after the streptavidin magnetic particles are magnetically captured onto the surface of the reaction well wall. The magnetic particles are washed three times with system wash buffer.

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Acridinium esters emit light upon treatment with hydrogen peroxide and an alkaline solution. The Trigger 1 solution contains hydrogen peroxide in dilute acid and Trigger 2 solution contains dilute sodium hydroxide. The system automatically injects Trigger 1 and 2 into the reaction well which oxidize the acridinium ester. The oxidized product is in an excited state. The subsequent return to ground state results in the emission of light which is quantified in 2 seconds, and is expressed in relative light units (RLU) by the integrated system luminometer.

The amount of bound labeled antibody in RLU's is directly proportional to the concentration of PSA in the sample. Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar codes.

#### 5. Intended Use:

Intended for use with the Nichols Advantage Specialty System for the quantitative determination of prostate specific antigen (PSA) in human serum and is to be used as an adjunct in the management of patients with prostate cancer.

#### Comparison to predicate device: 6.

The Nichols Advantage PSA is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Hybritech Tandem®-R PSA.

The following tables compare the Nichols Advantage™ PSA with the predicate device, Hybritech Tandem®-R PSA.

#### Similarities:

- . Intended Use: For the quantitative measurement of prostate specific antigen (PSA) and is to be use as an aid in the management of patients with prostate cancer.
- Both assays use mouse monoclonal antibodies to bind PSA molecules. .
- Both assays are based on two-site immunometric assay technique (sandwich assays). .
- Both assays use human serum for the test specimen. ●
- The sensitivity of the two assays are similar (0.1 ng/mL). ●

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## Differences:

| Feature: | Nichols Advantage™ PSA | Hybritech Tandem®-R PSA |
|----------------------------|------------------------------------------------------------------------------------|----------------------------------------------------------------|
| Sample Size | 20uL | 50uL |
| Detection Method | Acridinium labeled antibody.<br>RLU is the signal. | 125I labeled antibody<br>Gamma radiation in CPM is the signal. |
| Instrument<br>Requirements | Nichols Advantage Specialty<br>System | Gamma Photon System or gamma<br>counter. |
| Calibration: | Full calibration curve every 2<br>weeks with 2 point calibration<br>every 4 hours. | Full calibration curve with every<br>run. |
| Standardization | Stamey/Stanford Reference<br>Standard (90% PSA-ACT + 10%<br>free PSA) | Different reference material. |
| Solid Phase: | Streptavidin magnetic particles.<br>Streptavidin-biotin separation<br>technology. | Coated beads with anti-PSA<br>monoclonal antibody. |
| Reportable Range | 0-30 ng/mL | 0-100 ng/mL |

:

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# Performance Characteristics:

| Feature: | Nichols Advantage™ PSA | Hybritech Tandem®-R PSA | | | | |
|------------------------|------------------------------------------------|-------------------------|--------|----------------------------------|------|------|
| Precision: | | | | | | |
| | Intra-Assay: | | | Intra-Assay: | | |
| Level | Pool 1 | Pool 2 | Pool 3 | 1 | 2 | 3 |
| N | 20 | 20 | 20 | 40 | 40 | 40 |
| Mean (ng/mL) | 0.6 | 3.9 | 23.6 | 5.25 | 26.8 | 78.9 |
| %CV | 6.1 | 2.3 | 2.7 | 4.4 | 4.8 | 4.3 |
| | Inter-Assay: | | | Inter-Assay: | | |
| Level | Pool 4 | Pool 5 | Pool 6 | 1 | 2 | 3 |
| N | 20 | 20 | 20 | 40 | 40 | 40 |
| Mean (ng/mL) | 0.7 | 4.2 | 27.7 | 5.2 | 27.3 | 79.6 |
| %CV | 9.8 | 3.6 | 9.1 | 5.4 | 4.2 | 2.4 |
| Sensitivity | 0.1 ng/mL | | | 0.1 ng/mL | | |
| High Dose Hook | no hook effect up to 5,000 ng/mL | | | no hook effect up to 5,000 ng/mL | | |
| Recovery | 93-106% | | | 92-95% | | |
| Parallelism | 89-108% | | | not available | | |
| Interfering Subtances: | No interference up to: | | | No interference up to: | | |
| hemoglobin | 800 mg/dL | | | 200 mg/dL | | |
| bilirubin | 25 mg/dL | | | 25 mg/dL | | |
| lipemia(triglycerides) | 2325 mg/dL | | | 2320 mg/dL | | |
| PAP | 1,000 ng/mL | | | 1,000 ng/mL | | |
| Method Comparison | versus Hybritech Tandem-R PSA | | | | | |
| | n=183 split samples | | | | | |
| | Range of values 0.1 to 24.6 ng/mL (Hybritech) | | | | | |
| | Range of values 0.1 to 22.3 ng/mL (Nichols) | | | | | |
| | y = 0.974x + 0.25 (Deming linear regression) | | | | | |
| | 95% confidence of the slope: 0.906 - 1.042 | | | | | |
| | 95% confidence of the intercept: -0.34 to 0.84 | | | | | |
| | R = 0.885 | | | | | |

'

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular and features the department's name around the perimeter. In the center is a stylized symbol that resembles a caduceus, a symbol often associated with healthcare.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Nichols Institute Diagnostics c/o Ms. Cindy Martin Regulatory Consultant 1711 North Bush Street Santa Ana, California 92706

APR - 3 1998

Re: к980716

> Nichols Institute Diagnostics ADVANTAGE™ Trade Name: Chemiluminescence Prostate Specific Antigen (PSA) Immunoassay

Regulatory Class: II Product Code: LTJ Dated: January 5, 1998 Received: January 7, 1998

Dear Ms. Martin:

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 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: requirement; as set forth was now 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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Page 2

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 at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.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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# INDICATIONS FOR USE STATEMENT

11-880116 K965031

510(K) Number (if known):

Nichols Advantage™ Chemiluminescence Assay Prostate Specific Device Name: Antigen

#### Indications For Use:

Intended for use with the Nichols Advantage Specialty System for the quantitative determination of prostate specific antigen (PSA) in human serum and is to be used as an adjunct in the management of patients with prostate cancer.

Peter E. Maples

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

( 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-Counter Use (Optional Format 1-2-96)

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