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 Description

The Nichols Advantage™ PSA is a two-site chemiluminescence assay. Total duration of assay is 30 minutes at 37ºC.
1st 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.
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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study information for the Nichols Advantage™ Chemiluminescence Prostate Specific Antigen Assay, based on the provided text:

Acceptance Criteria and Reported Device Performance

Feature	Acceptance Criteria (Implied by Predicate)	Nichols Advantage™ PSA Performance
Precision:
Intra-Assay	%CV similar to predicate (e.g., 4.3-4.8% for higher concentrations)	Pool 1 (0.6 ng/mL): 6.1% CVPool 2 (3.9 ng/mL): 2.3% CVPool 3 (23.6 ng/mL): 2.7% CV
Inter-Assay	%CV similar to predicate (e.g., 2.4-5.4% for higher concentrations)	Pool 4 (0.7 ng/mL): 9.8% CVPool 5 (4.2 ng/mL): 3.6% CVPool 6 (27.7 ng/mL): 9.1% CV
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	92-95%	93-106%
Parallelism	Not available for predicate (implies demonstrating acceptable parallelism for the new device will suffice)	89-108%
Interfering Substances	No interference up to at least the levels of the predicate (e.g., hemoglobin 200 mg/dL, bilirubin 25 mg/dL, lipemia 2320 mg/dL, PAP 1,000 ng/mL)	Hemoglobin: 800 mg/dLBilirubin: 25 mg/dLLipemia (triglycerides): 2325 mg/dLPAP: 1,000 ng/mL
Method Comparison (vs. Predicate)	Strong correlation (R-value) and close agreement in values (slope near 1, intercept near 0)	n=183 split samplesRange (Hybritech): 0.1 to 24.6 ng/mLRange (Nichols): 0.1 to 22.3 ng/mLy = 0.974x + 0.2595% CI slope: 0.906 - 1.04295% CI intercept: -0.34 to 0.84R = 0.885

(Note: The acceptance criteria are "implied" based on the comparison to the predicate device. For diagnostic assays, achieving comparable or better performance characteristics than a legally marketed predicate is the standard for substantial equivalence.)

Study Details:

Sample Size used for the test set and the data provenance:
- Method Comparison Test Set: n=183 split samples.
- Data Provenance: Not explicitly stated (e.g., country of origin), but the samples were described as "human serum" for PSA determination. The study is retrospective in the sense that existing samples within a certain range were used for testing, but it's not specified if they were collected specifically for this study or were banked samples.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not provided in the document. For in-vitro diagnostic (IVD) devices like this PSA assay, the "ground truth" for the test set in method comparison studies is typically the measurement obtained from the predicate device itself. The primary goal is to show agreement with the established predicate, rather than using external experts for "ground truth."
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- This concept is not applicable for this type of IVD method comparison study. Adjudication methods like 2+1 are typically used in imaging or clinical outcome studies where there's subjective interpretation or a need to resolve discrepancies between multiple human readers/assessments. Here, the comparison is directly between two quantitative analytical devices.
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:
- No, an MRMC comparative effectiveness study was not done. This device is a quantitative in-vitro diagnostic immunoassay, not an AI-assisted diagnostic tool that aids human readers. Therefore, the concept of human readers improving with AI assistance is not relevant to this submission.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance characteristics presented (precision, sensitivity, recovery, parallelism, interference, and method comparison) represent the standalone performance of the device (instrument and reagents). The Nichols Advantage™ PSA assay is a fully automated system that delivers quantitative results directly, without human interpretation as part of the primary diagnostic output (though a clinician interprets the numerical result in the context of a patient's overall health).
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" for the method comparison study was the Hybritech Tandem®-R PSA, the predicate device. The study aims to demonstrate substantial equivalence by correlating the new device's results with those of the legally marketed predicate. For other performance metrics (like precision, sensitivity, recovery), the "ground truth" is established by standard laboratory practices and reference materials.
The sample size for the training set:
- This information is not provided in the document. For a traditional immunoassay device like this, the term "training set" in the context of deep learning or AI algorithms is not directly applicable. However, the device would have undergone extensive validation and development, which involves numerous samples used to optimize reagents, instrument parameters, and calibration curves. These would be internal R&D samples, not explicitly termed a "training set" in this context. The document only covers the performance characteristics of the finalized product.
How the ground truth for the training set was established:
- As mentioned above, the concept of a "training set" and establishing its "ground truth" in the AI sense is not directly applicable here. For the development and optimization of the assay, the "ground truth" would be established through careful analytical studies using:
  - Reference materials/calibrators with known PSA concentrations.
  - Clinical samples characterized by established methods (e.g., the predicate device) or clinical diagnosis.
  - Spiking studies where known amounts of PSA are added to samples to assess recovery.
  - These processes ensure the assay accurately measures PSA levels, which forms the basis for its intended use.

Summary

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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

Name of Submitter, Contact Person and Date Summary prepared:

Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, California 92675 Phone: 714-240-5260 Fax: 714-240-5313

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

1. 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:

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.RLU is the signal.	125I labeled antibodyGamma radiation in CPM is the signal.
InstrumentRequirements	Nichols Advantage SpecialtySystem	Gamma Photon System or gammacounter.
Calibration:	Full calibration curve every 2weeks with 2 point calibrationevery 4 hours.	Full calibration curve with everyrun.
Standardization	Stamey/Stanford ReferenceStandard (90% PSA-ACT + 10%free PSA)	Different reference material.
Solid Phase:	Streptavidin magnetic particles.Streptavidin-biotin separationtechnology.	Coated beads with anti-PSAmonoclonal 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 (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 regulation (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 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:

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)

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

ﻬﺎ

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.