ELECSYS PSA ASSAY

K964351 · Boehringer Mannheim Corp. · LTJ · Jul 25, 1997 · Immunology

Device Facts

• Record ID: K964351
• Device Name: ELECSYS PSA ASSAY
• Applicant: Boehringer Mannheim Corp.
• Product Code: LTJ · Immunology
• Decision Date: Jul 25, 1997
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

Immunoassay for the in vitro quantitative determination of Prostate-Specific Antigen in human serum and plasma. The Elecsys PSA assay is further indicated for serial measurement of PSA to aid in the management of prostate cancer. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzers.

Device Story

Elecsys PSA Assay is an in vitro diagnostic immunoassay for quantitative PSA measurement in human serum and plasma; used on Elecsys 2010 analyzers in clinical laboratory settings. Principle: sandwich immunoassay using biotinylated monoclonal PSA-specific antibody and ruthenium-labeled monoclonal PSA-specific antibody. Sample (40 μL) incubated with antibodies (60 μL each) for 9 minutes; streptavidin-coated microparticles (40 μL) added for second 9-minute incubation to bind complex to solid phase. Reaction mixture aspirated into measuring cell; microparticles magnetically captured on electrode surface. Unbound substances removed via ProCell; voltage applied to electrode induces chemiluminescent emission measured by photomultiplier. Results calculated via instrument-specific calibration curve and master curve from reagent bar code. Output aids clinicians in prostate cancer management through serial PSA monitoring.

Clinical Evidence

Bench testing only. Performance evaluated via precision (N=60 per control/pool), linearity (0.01-100 ng/mL), and method comparison against TOSOH AIA-PACK PA (N=365, r=0.995). Functional sensitivity 0.07 ng/mL. Interference testing performed for bilirubin, hemoglobin, lipemia, and biotin. No hook effect observed up to 13,900 ng/mL.

Technological Characteristics

Electrochemiluminescence immunoassay (ECLIA). Sandwich immunoassay principle. Uses biotinylated monoclonal antibodies and ruthenium-labeled monoclonal antibodies. Solid phase: streptavidin-coated microparticles. Detection: photomultiplier measurement of chemiluminescent emission upon voltage application. Connectivity: reagent bar code for master curve input. Designed for Elecsys 2010 immunoassay analyzers.

Indications for Use

Indicated for in vitro quantitative determination of Prostate-Specific Antigen (PSA) in human serum and plasma to aid in the management 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

• TOSOH AIA-PACK PA

Submission Summary (Full Text)

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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
JUL 25 1997
Food and Drug Administration
2098 Gaither Road
Rockville MD 20850

Boehringer Mannheim Corporation
Laboratory Diagnostics Division
c/o Ms. Mary Koning, Regulatory Affairs Specialist
2400 Bisso Lane
P.O. Box 4117
Concord, California 94524

Re: K964351/S1
Trade Name: Elecsys® PSA Assay
Regulatory Class: II
Product Code: LTJ
Dated: May 12, 1997
Received: May 13, 1997

Dear Ms. Koning:

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 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 at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

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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JUL 25 1997
K964351

BOEHRINGER MANNHEIM CORPORATION

510(k) Summary


| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
| --- | --- |
| 1. Submitter name, address, contact | Boehringer Mannheim Corporation
2400 Bisso Lane
P.O. Box 4117
Concord, CA 94524-4117
(510) 674 - 0690, extension 8415

Contact Person: Mary Koning

Date Prepared: October 31, 1996 |
| 2. Device name | Proprietary name: Elecsys® PSA Assay

Common name: Electrochemiluminescence 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 TOSOH AIA-PACK PA. |
| 4. Device Description | The Elecsys® test principle is based on sandwich principle. Total duration of assay: 18 minutes (37° C).
•1st incubation (9 minutes): Sample (40 μL), a biotinylated monoclonal PSA-specific antibody (60 μL), and a monoclonal PSA-specific antibody labeled with a ruthenium complex (60 μL) react to form a sandwich complex.
•2nd incubation (9 minutes): After addition of streptavidin-coated microparticles (40 μL), the entire complex is bound to the solid phase via interaction of biotin and streptavidin. |

Continued on next page

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510(k) Summary, Continued
K 964351

4. Device Description
- The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame).
- 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 code.

5. Intended use
Immunoassay for the in vitro quantitative determination of Prostate-Specific Antigen in human serum and plasma to aid in the management of prostate cancer patients.

6. Comparison to predicate device
The Boehringer Mannheim Elecsys® PSA Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed TOSOH AIA-PACK PA.
The following table compares the Elecsys® PSA Assay with the predicate device, TOSOH AIA-PACK PA. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device is provided in attachment 6.

Similarities:
- Intended Use: Immunoassay for the in vitro quantitative determination of prostate-specific antigen. The assay is further indicated for serial measurement of PSA to aid in the management of cancer patients.
- Assay range: 0-100 ng/ml
- Assay methodology: Sandwich immunoassay
- Cross-Reactivity: 0% to PAP

Continued on next page

page 26

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510(k) Summary, Continued
K 964351

6. Comparison to predicate device cont.

## Differences:

| Feature | Elecsys® PSA | AIA-PACK PA |
| --- | --- | --- |
| Reaction test principle | Electrochemiluminescence | Two-site immuno-enzymometric assay |
| Sample | Serum and Plasma | Serum |
| Instrument required | Elecsys® 2010 | AIA-1200/AIA 600 |
| Assay Standardization | Stanford Reference Standard (90% PSA-ACT + 10% free PSA) | Different Material - Stanford Reference Standard was unavailable at time of assay development |
| Calibration Stability | A calibration is recommended every 7 days if kit is not consumed; 8 weeks with same reagent lot if reagent is consumed within 7 days. | A calibration is required every 30 days. |

## Performance Characteristics:

| Feature | Elecsys® PSA | | | AIA-PACK PA | | |
| --- | --- | --- | --- | --- | --- | --- |
| Precision Level | Modified NCCLS (ng/mL): | | | Precision (ng/mL): | | |
| | Control 1 | Control 2 | Pool 1 | A | B | C |
| N | 60 | 60 | 60 | 20 | 20 | 20 |
| Within-Run | 1.88 | 14.00 | 0.29 | 6.61 | 51.68 | 95.10 |
| %CV | 1.1 | 1.2 | 1.5 | 2.9 | 3.9 | 3.0 |
| Total | 1.88 | 14.00 | 0.29 | 6.52 | 52.26 | 98.33 |
| %CV | 2.1 | 2.2 | 2.9 | 2.1 | 3.9 | 2.8 |
| | Modified NCCLS (ng/mL): | | | | | |
| | Pool 2 | Pool 3 | | | | |
| N | 60 | 60 | | | | |
| Within-Run | 3.95 | 48.48 | | | | |
| %CV | 1.8 | 1.6 | | | | |
| Total | 3.95 | 48.48 | | | | |
| %CV | 2.3 | 2.3 | | | | |

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page 27

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510(k) Summary, Continued
K 964351

6. Comparison to predicate device, (cont.)

Performance Characteristics:

| Feature | Elecsys® PSA | AIA-PACK PA |
| --- | --- | --- |
| Lower Detection Limit | 0.01 ng/mL
Functional: 0.07 ng/mL | 0.1 ng/mL |
| Linearity | 0.01 - 100 ng/mL (with a deviation from a linear line of ±10%) | 0.1 - 100 ng/mL |
| Method Comparison | Vs TOSOH AIA-PACK PA
**Least Squares**
y =0.86x + 0.01
r=0.995
SEE = 0.251
N=365

**Passing/Bablok**
y =0.90x - 0.28
r=0.995
SEE = 0.892
N=365 | Not shown |
| Interfering substances
Bilirubin
Hemoglobin
Lipemia
Biotin | No interference at:
25 mg/dL
1.0 g/dL
1000 mg/dL
30 ng/mL | No interference at:
17 mg/dL
0.47 g/dL
1600 mg/dL |
| Specificity
PAP
ACT
PSA
PSA-ACT | % Cross-reactivity
none
none
100%
100% | % Cross-reactivity
0.0
not available
not available
not available |
| Hook Effect | No Hook Effect up to 13,900 ng/ml PSA | Not available |

Continued on next page

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JUL 18 '97 01:36PM EM REG
P.5

510(k) Number (if known): K964351
Device Name: Elecsys® PSA Assay
Indications for Use:

Immunoassay for the in vitro quantitative determination of Prostate-Specific Antigen in human serum and plasma. The Elecsys PSA assay is further indicated for serial measurement of PSA to aid in the management of prostate cancer.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzers.


(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K964351

(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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