The Nichols Advantage® Bio-Intact PTH (1-84) Immunoassay is intended for use with the Nichols Advantage® Specialty System to measure the levels of parathyroid hormone in serum, EDTA plasma and heparinized plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism. Measurements of parathyroid hormone levels with the Bio-Intact PTH (1-84) Immunoassay are also used as an aid in monitoring therapeutic intervention of secondary hyperparathyroidism that frequently occurs in chronic kidney disease. Assay results should be used in conjunction with other clinical data to assist the clinician in making individual patient management decisions.

Device Description

The Bio-Intact PTH (1-84) Assay is a two-site chemiluminescence assay for use with the Nichols Advantage® Specialty System.

AI/ML Overview

Here's a summary of the acceptance criteria and study information for the Nichols Advantage® Bio-Intact PTH (1-84) Immunoassay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The submission describes the device as a modification of a predicate device (K013992). The acceptance criteria are implicit in the comparison to the predicate device and the reported performance characteristics.

Feature	Acceptance Criteria (Predicate K013992)	Reported Device Performance (Modified Bio-Intact PTH (1-84) Assay)
Precision
Within Run CV	Not greater than 4% at dose > 5 pg/mL	Not greater than 6% at a dose > 5 pg/mL
Total CV	Not greater than 9.5% at dose > 34 pg/mL	Not greater than 11% at a dose > 5 pg/mL
Method Comparison 1 (Serum Analysis)
Sample Size	305	305
Range of Results	Nichols Advantage Intact PTH Assay: 5.0 to 1387 pg/mL Bio-Intact PTH (1-84) Assay: 3.0 to 746 pg/mL	Nichols Advantage Intact PTH Assay: 5.0 to 1387 pg/mL Bio-Intact PTH (1-84) Assay: 3.0 to 746 pg/mL
Passing Bablok Regression Equation	y = 0.66x - 0.6	y = 0.66x - 0.6
Least Squares Linear Regression Equation	y = 0.60x + 4.2	y = 0.60x + 4.2
Pearson's Correlation Coefficient (r)	0.97	0.97
Method Comparison 2 (Renal Dialysis Samples)	N/A
Sample Size	N/A	3187
Range of Results	N/A	Nichols Advantage Intact PTH Assay: 7 - 1797 pg/mL Bio-Intact PTH (1-84) Assay: 4 - 998
Least Squares Linear Regression Equation	N/A	Y = 0.52x + 1.3
Pearson's Correlation Coefficient (r)	N/A	0.97

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

Method Comparison 1 (Serum Analysis):
- Sample Size: 305
- Data Provenance: Not explicitly stated, but clinical samples are implied for method comparison. The text does not specify country of origin or if prospective/retrospective.
Method Comparison 2 (Renal Dialysis Samples):
- Sample Size: 3187
- Data Provenance: Not explicitly stated. Clinical samples from renal dialysis patients are implied. The text does not specify country of origin or if prospective/retrospective.

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

This is an in vitro diagnostic (IVD) immunoassay. The concept of "experts" establishing ground truth as in imaging or clinical diagnosis is not directly applicable. The ground truth for method comparison studies in IVDs is typically established by the predicate device or a reference method. In this case, the Nichols Advantage Intact PTH Assay (the predicate device, K013992) served as the comparator for method comparison studies.

4. Adjudication Method for the Test Set

Not applicable for this type of IVD immunoassay study. The comparison is quantitative against a 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 immunoassay, not an imaging or interpretive device that involves human "readers" or "AI assistance."

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

This device is a standalone algorithm/device. Its performance is measured directly by its ability to quantify PTH levels in biological samples. It operates without human interpretive input in the measurement process itself, although clinical interpretation of results requires a human. The performance metrics (precision, method comparison) are standalone device metrics.

7. The Type of Ground Truth Used

The "ground truth" for demonstrating substantial equivalence and performance characteristics was established by:

Quantitative values obtained from the predicate device: The Nichols Advantage Intact PTH Assay was used as the comparator for the method comparison studies.
Established analytical methods: Precision, sensitivity, linearity, etc., are measured against established performance specifications for immunoassays.

8. The Sample Size for the Training Set

The provided text only details the performance studies for the modified device. It does not contain information about a separate "training set" for an algorithm in the way machine learning models would have one. For an immunoassay, method development and optimization would involve numerous samples, but these are not typically reported as a "training set" in a 510(k) summary.

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

As above, the concept of a "training set" with established ground truth as in machine learning does not directly apply to this immunoassay submission. Assay development and validation would rely on known control materials, spiked samples, and comparison to established reference methods or predicate devices during the R&D phase to optimize assay parameters.

Summary

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12.0 510(k) SUMMARY

K033727

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

510(k) Number: Not Known

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

Nichols Institute Diagnostics 1311 Calle Batido San Clemente, CA 92673 Phone: 949-940-7417 Fax: 949-940-7440

Contact Person: Robert L. Schmidt Date Prepared: November 25, 2003

2. Device Name

Trade/Proprietary Name:	Nichols Advantage® Bio-Intact PTH (1-84) Immunoassay
Common/Usual Name:	Bio-Intact PTH (1-84) Assay
Classification Name:	Radioimmunoassay, Parathyroid Hormone

3. Predicate Device:

The device that is the subject of this submission is substantially equivalent to the Nichols Advantage® Bio-Intact (1-84) PTH Immunoassay (K013992; Cleared 12/31/01). This 510(k) is for labeling changes to the predicate device.

4. Device Description:

The Bio-Intact PTH (1-84) Assay is a two-site chemiluminescence assay for use with the Nichols Advantage® Specialty System.

5. Intended Use

The Nichols Advantage® Bio-Intact PTH (1-84) immunoassay is intended for use with the Nichols Advantage Specialty System to measure the levels of parathyroid hormone in serum, EDTA plasma and heparinized plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism. Measurements of parathyroid hormone levels with the Bio-Intact PTH (1-84) Immunoassay are also used as an aid in monitoring therapeutic intervention of secondary hyperparathyroidism that frequently occurs in chronic kidney disease. Assay results should be

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used in conjunction with other clinical data to assist the clinician in making individual patient management decisions.

6. Comparison to predicate device:

The Bio-Intact PTH (1-84) Assay is substantially equivalent to the Nichols Advantage Bio-Intact PTH(1-84) Immunoassay previously submitted as K013992. The following tables compare the Bio-Intact PTH (1-84) Assay (modified) with the predicate device, the Nichols Advantage Bio-Intact PTH (1-84) Immunoassay (K013992).

Similarities:

Intended Use: For the quantitative determination of intact PTH in human serum or EDTA . plasma.
Both assays use specific antibodies to bind intact PTH. .
Both assays can use human serum or EDTA plasma for the test sample. .
Both assays use chemiluminometric technology based on acridinium esters. .
Both assays use 150 microliters of sample. .
Both assays use two point calibration every two weeks (maximum) of stored working . calibration curve; or when controls out of range.
Both assays use Streptavidin-coated magnetic particles and streptavidin-biotin separation . technology.
Both assays' total incubation period is 30 minutes at 37℃. .
The sensitivity of both assays is 1.5 pg/mL. (analytical) and 4.0 pg/mL (functional). ♥
. The throughput is the same for both assays at 180 test/hour.
. The cross reactives are the same between assays.
. The recovery is the same between assays.
The parallelism is the same between assays. .
The high dose hook effect is the same between assays. .

Differences:

Intended Use: The Nichols Advantage® Bio-Intact PTH (1-84) Immunoassay is intended for use with the Nichols Advantage® Specialty System to measure the levels of parathyroid hormone in serum, EDTA plasma and heparinized plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism. Measurements of parathyroid hormone levels with the Bio-Intact PTH (1-84) Immunoassay are also used as an aid in monitoring therapeutic intervention of secondary hyperparathyroidism that frequently occurs in chronic kidney disease. Assay results should be used in conjunction with other clinical data to assist the clinician in making individual patient management decisions.

The modified device includes data on preanalytical variables for serum, EDTA plasma, ● heparinized plasma and EDTA whole blood.

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Performance Characteristics:
FEATURE	Nichols Advantage®Bio-Intact PTH (1-84)Immunoassay(K013992)	Bio-Intact PTH (1-84) Assay(K033302)*	Bio-Intact PTH (1-84) Assay(Modified)
PrecisionwithinRun	Not greater than 4% atdose greater than 5pg/mL	Not greaterthan 6% at adose greaterthan 5 pg/mL	Not greaterthan 6% at adose greaterthan 5 pg/mL
PrecisionTotal	Not greater than 9.5%at dose greater than 34pg/mL	Not greaterthan 11% at adose greaterthan 5 pg/mL	Not greaterthan 11% at adose greaterthan 5 pg/mL
*K033302 was submitted October 14, 2003 and is under review.
Method Comparison 1 - Serum Analysis Nichols Advantage Intact PTH Assay Vs. Bio-Intact PTH (1-84) Assay
FEATURE	Nichols Advantage® Bio-IntactPTH (1-84) Immunoassay(K013992)	Bio-Intact PTH (1-84) Assay(Modified)
Sample Size:	305	305
Range ofResults:	Nichols Advantage Intact PTHAssay: 5.0 to 1387 pg/mLNichols Advantage Bio-IntactPTH (1-84) Assay: 3.0 to 746pg/mL	Nichols Advantage Intact PTH Assay: 5.0 to1387 pg/mLNichols Advantage Bio-Intact PTH (1-84) Assay: 3.0to 746 pg/mL
Passing BablokRegressionEquation:	y = 0.66x - 0.6	y = 0.66x - 0.6
Least SquaresLinearRegressionEquation:	y = 0.60x + 4.2	y = 0.60x + 4.2
Pearson'sCorrelationCoefficient (r):	0.97	0.97
Method Comparison 2 - Renal Dialysis Samples Nichols Advantage Intact PTH Assay Vs. Bio-IntactPTH (1-84) Assay
FEATURE	Nichols Advantage® Bio-IntactPTH (1-84) Immunoassay(K013992)	Bio-Intact PTH (1-84) Assay(Modified)
Sample Size:	N/A	3187
Range of results:	N/A	Nichols Advantage Intact PTH Assay:7 - 1797pg/mLNichols Advantage Bio-Intact PTH (1-84) Assay 4-998
Least Squares Linear Regression Equation:	N/A	$Y = 0.52 x + 1.3$
Pearson's Correlation Coefficient (r):	N/A	0.97

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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 stylized eagle or bird-like figure with three curved lines representing its body and wings. The logo is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" in a circular arrangement.

Public Health Service

APR 2 2 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Robert L. Schmidt Director of Quality Nichols Institute Diagnostics 1311 Calle Batido San Clemente, CA 92673

K033727 Re:

Trade/Device Name: Nichols Advantage® Bio-Intact PTH (1-84) Immunoassay Regulation Number: 21 CFR 862.1545 Regulation Name: Parathyroid hormone test system Regulatory Class: Class II Product Code: CEW Dated: March 18, 2004 Received: March 19, 2004

Dear Mr. Schmidt:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, ITDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a dctermination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practicc requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Jean M. Cooper, MS, DVM.

Yean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE STATEMENT )

INDICATIONS FOR USE STATEMENT

K033727 510(k) Number (if known):

Device Name: Nichols Advantage® Bio-Intact PTH (1-84) Immunoassay

Indications For Use:

Prescription Use
(Per 21 CFR 801.109) ✓

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Albert C

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K033721

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Regulation Number and Section

§ 862.1545 Parathyroid hormone test system.

(a)
Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.(b)
Classification. Class II.