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.

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 uL), 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 uL), the entire complex is bound to the solid phase via interaction of biotin and streptavidin.
•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.

AI/ML Overview

Here's an analysis of the provided text to extract the acceptance criteria and study details for the Elecsys® PSA Assay, structured according to your request:

Device: Elecsys® PSA Assay

1. Table of Acceptance Criteria and Reported Device Performance

The document provided (a 510(k) summary) doesn't explicitly state "acceptance criteria" as pass/fail thresholds for clinical performance but instead compares the performance of the applicant device (Elecsys® PSA) to a legally marketed predicate device (TOSOH AIA-PACK PA). The comparison highlights key performance characteristics. I will interpret the predicate device's performance as a de facto benchmark for "acceptance criteria" in this context, and the Elecsys® PSA's performance as the "reported device performance."

Feature	Acceptance Criteria (Predicate: TOSOH AIA-PACK PA)	Reported Device Performance (Elecsys® PSA)
Precision		Modified NCCLS (ng/mL):
Level A (Predicate Equiv.)	Within-Run: 6.61, %CV: 2.9, Total: 6.52, %CV: 2.1	Control 1: Within-Run: 1.88, %CV: 1.1, Total: 1.88, %CV: 2.1
Level B (Predicate Equiv.)	Within-Run: 51.68, %CV: 3.9, Total: 52.26, %CV: 3.9	Control 2: Within-Run: 14.00, %CV: 1.2, Total: 14.00, %CV: 2.2
Level C (Predicate Equiv.)	Within-Run: 95.10, %CV: 3.0, Total: 98.33, %CV: 2.8	Pool 1: Within-Run: 0.29, %CV: 1.5, Total: 0.29, %CV: 2.9 (Note: Predicate values are higher and in different units; direct comparison is difficult without context)
		Pool 2: Within-Run: 3.95, %CV: 1.8, Total: 3.95, %CV: 2.3
		Pool 3: Within-Run: 48.48, %CV: 1.6, Total: 48.48, %CV: 2.3
Lower Detection Limit	0.1 ng/mL	0.01 ng/mL (Functional: 0.07 ng/mL)
Linearity	0.1 - 100 ng/mL	0.01 - 100 ng/mL (with a deviation from a linear line of ±10%)
Method Comparison	Not shown (TOSOH AIA-PACK PA)	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
Interfering substances
Bilirubin	No interference at 17 mg/dL	No interference at 25 mg/dL
Hemoglobin	No interference at 0.47 g/dL	No interference at 1.0 g/dL
Lipemia	No interference at 1600 mg/dL	No interference at 1000 mg/dL
Biotin	Not specified	No interference at 30 ng/mL
Specificity
PAP	0.0% cross-reactivity	None
ACT	Not available	None
PSA	Not available	100%
PSA-ACT	Not available	100%
Hook Effect	Not available	No Hook Effect up to 13,900 ng/ml PSA

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size:
- Precision:
  - Elecsys® PSA: 60 measurements per control/pool (Control 1, Control 2, Pool 1, Pool 2, Pool 3), implying a total of 300 measurements across 5 levels.
  - TOSOH AIA-PACK PA: 20 measurements per precision level (A, B, C), implying a total of 60 measurements across 3 levels.
- Method Comparison: N = 365 (for comparison with TOSOH AIA-PACK PA).
Data Provenance: The document does not specify the country of origin for the data or whether the studies were retrospective or prospective. It is a 510(k) submission, typically involving studies conducted by the manufacturer, but clinical trial details are absent.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of information is generally not applicable to in vitro diagnostic (IVD) devices like the Elecsys® PSA Assay. For IVDs, "ground truth" is established through reference methods, calibrated materials, or comparison to an accepted predicate device, rather than expert consensus on individual cases. The document does not mention any expert review process for establishing ground truth.

4. Adjudication Method for the Test Set

Not applicable. As this is an IVD device measuring an analyte (PSA), there is no "adjudication method" in the sense of multiple experts reviewing and reaching consensus on an outcome. The performance is assessed by comparing quantitative results to a reference method or predicate device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

Not applicable. This is an in vitro diagnostic assay, not an AI-powered image analysis or diagnostic assist device that involves "human readers" or "AI assistance" in the clinical interpretation of images or complex datasets.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the performance data presented (precision, linearity, lower detection limit, method comparison, interference, specificity, hook effect) represents the standalone performance of the Elecsys® PSA assay. It is an automated electrochemiluminescence immunoassay, meaning its results are generated by the instrument and reagents without direct human interpretative intervention in the final measurement.

7. The Type of Ground Truth Used

The ground truth for performance characteristics of an IVD like this is generally established by:

Reference Materials/Calibrators: For accuracy and calibration stability, the device's measurements are calibrated against known standard materials (e.g., Stanford Reference Standard is mentioned as "Assay Standardization" for the Elecsys® PSA).
Comparison to a Legally Marketed Predicate Device: For substantial equivalence, the new device's performance is compared against an existing, accepted device (TOSOH AIA-PACK PA in this case) using patient samples. The predicate's results serve as a form of "ground truth" for the comparison study.
Specific Analytical Methods: Linearity is assessed against expected values for diluted samples, detection limits against statistical variations at low concentrations, and interference against known concentrations of interfering substances.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" sample size. For IVD devices, a "training set" in the machine learning sense is not typically used. Instead, methods are developed and optimized by the manufacturer using internal data, reagents, and instrument prototypes. The data presented in the 510(k) is akin to verification and validation data.

9. How the Ground Truth for the Training Set Was Established

Not applicable. As mentioned, the concept of a "training set" with established ground truth as in machine learning does not directly translate to the development and validation of traditional IVD assays like the Elecsys® PSA. Assay parameters are optimized based on biochemical principles, empirical testing, and calibration with reference materials.

Summary

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of three curved lines.

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 Elecsys® PSA Assay Trade Name: Requlatory 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 requlatory 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 (CDIA-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 (770)488-7655.

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 requlation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/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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JUL 2 5 1997

长964351

BOEHRINGER MANNHEIM CORPORATION

Introduction

510(k) Summary

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 Corporation2400 Bisso LaneP.O. Box 4117Concord, CA 94524-4117(510) 674 - 0690, extension 8415Contact Person: Mary KoningDate Prepared: October 31, 1996
2. Device name	Proprietary name: Elecsys® PSA AssayCommon 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 uL), 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 uL), the entire complex is bound to the solid phase via interaction of biotin and streptavidin.

Continued on next page:

page 25

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510(k) Summary, Continued

{

ﻟﺴﻌﺮ

4.DeviceDescription	•The reaction mixture is aspirated into the measuring cell where themicroparticles are magnetically captured onto the surface of the electrode.Unbound substances are then removed with ProCell. Application of a voltageto the electrode then induces chemiluminescent emission which is measuredby 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 viathe reagent bar code.	Feature	Elecsys® PSA	AIA-PACK PA
5.Intended use	Immunoassay for the in vitro quantitative determination of Prostate-SpecificAntigen in human serum and plasma to aid in the management of prostatecancer patients.	Reaction testprinciple	Electrochemiluminescence	Two-site immuno-enzymometric assay
6.Comparisonto predicatedevice	The Boehringer Mannheim Elecsys® PSA Assay is substantially equivalentto other products in commercial distribution intended for similar use. Mostnotably it is substantially equivalent to the currently marketed TOSOH AIA-PACK PA.The following table compares the Elecsys® PSA Assay with the predicatedevice, TOSOH AIA-PACK PA. Specific data on the performance of the testhave been incorporated into the draft labeling in attachment 5. Labeling forthe predicate device is provided in attachment 6.	Sample	Serum and Plasma	Serum
Similarities:		Instrumentrequired	Elecsys® 2010	AIA-1200/AIA 600
	•Intended Use: Immunoassay for the in vitro quantitative determinationof prostate-specific antigen. The assay is further indicated for serialmeasurement of PSA to aid in the management of cancer patients.	AssayStandardization	Stanford Reference Standard(90% PSA-ACT + 10% freePSA)	Different Material - StanfordReference Standard wasunavailable at time of assaydevelopment
	•Assay range: 0-100 ng/ml	CalibrationStability	A calibration is recommendedevery 7 days if kit is notconsumed; 8 weeks with samereagent lot if reagent isconsumed within 7 days.	A calibration is required every30 days.
	•Assay methodology: Sandwich immunoassay
	•Cross-Reactivity: 0% to PAP
	Continued on next page

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510(k) Summary, Continued

Differences:

Comparison to predicate
device cont.

Performance Characteristics:

Feature	Elecsys® PSA			AIA-PACK PA
PrecisionLevel	Modified NCCLS (ng/mL):Control 1	Modified NCCLS (ng/mL):Control 2	Modified NCCLS (ng/mL):Pool 1	Precision (ng/mL):A	Precision (ng/mL):B	Precision (ng/mL):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

Continued on next page page 27

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K964351

510(k) Summary, Continued

Comparison
to predicate device, (cont.)

Performance Characteristics:

Feature	Elecsys® PSA	AIA-PACK PA
LowerDetectionLimit	0.01 ng/mLFunctional: 0.07 ng/mL	0.1 ng/mL
Linearity	0.01 - 100 ng/mL (with adeviation from a linear line of±10%)	0.1 - 100 ng/mL
MethodComparison	Vs TOSOH AIA-PACK PALeast Squares$y =0.86x + 0.01$r=0.995SEE = 0.251N=365Passing/Bablok$y =0.90x - 0.28$r=0.995SEE = 0.892N=365	Not shown
Interferingsubstances	No interference at:	No interference at:
Bilirubin	25 mg/dL	17 mg/dL
Hemoglobin	1.0 g/dL	0.47 g/dL
Lipemia	1000 mg/dL	1600 mg/dL
Biotin	30 ng/mL
Specificity	% Cross-reactivity	% Cross-reactivity
PAP	none	0.0
ACT	none	not available
PSA	100%	not available
PSA-ACT	100%	not available
Hook Effect	No Hook Effect up to13.900 ng/ml PSA	Not available

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

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

Peter E. Maler

Division Sign-Off Division of Clinical 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)

Over-The Counter-Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.6010 Tumor-associated antigen immunological test system.

(a)
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.(b)
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.