The Nichols Advantage® Chemiluminescence Intact Parathyroid Hormone Immunoassay is intended for use with the Nichols Advantage Specialty System for the quantitative determination of intact 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 intact parathyroid hormone levels 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 Nichols Advantage Intact PTH assay contains sufficient reagents for 100 tests. The assay is a two-site chemiluminometric assay specific for Intact PTH.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the Nichols Advantage® Chemiluminescence Intact Parathyroid Hormone device:

Based on the provided 510(k) summary, the device is an immunoassay for quantitative determination of intact parathyroid hormone (PTH). The primary purpose of this type of submission (510(k)) is to demonstrate substantial equivalence to a predicate device, rather than to establish a new clinical utility or performance against fixed acceptance criteria in a novel clinical study.

The "acceptance criteria" in this context are not defined as specific performance thresholds (e.g., sensitivity, specificity, accuracy) against a clinical gold standard, but rather relate to the demonstration that the modified device performs similarly to or better than the predicate device, and that the modifications do not introduce new safety or effectiveness concerns.

The summary states: "The device with modified labeling is substantially equivalent to the predicate device."

Here's a breakdown of the information requested, based on the provided document:

1. A table of acceptance criteria and the reported device performance

Given the nature of a 510(k) for an immunoassay where the core technology is unchanged and the focus is on demonstrating equivalence after minor modifications, the "acceptance criteria" are implied comparisons to the predicate device's established performance or confirmation of expected analytical characteristics.

Acceptance Criteria (Implied)	Reported Device Performance
Equivalence to Predicate Device for new specimen matrix: Expanded specimen types (heparinized plasma) should yield results essentially equivalent to those obtained with existing accepted specimen types (serum, EDTA plasma) or the predicate device.	- Heparinized plasma was added to the specimen matrix for Intact PTH testing.
Compatibility with Blood Collection Tubes: Use of different blood collection tubes should not significantly impact results.	- Use of 6 different blood collection tubes was compared for similarities and differences for Intact PTH testing, and results of comparative testing yield essentially equivalent results.
Specimen Stability: New specimen types (EDTA plasma, heparinized plasma) and serum should have established stability data.	- Specimen stabilities have been included in the new labeling for EDTA plasma, Heparinized plasma, and serum testing. (The document doesn't provide the duration of stability, just that it's included in labeling).
Clinical Utility Justification: Updated labeling for use in chronic kidney disease patients should be supported by scientific references.	- New labeling and scientific references supporting use of Intact PTH testing in patients with chronic kidney diseases were added. (The document doesn't list the references, only states they were added).
Cross-reactivity: The assay should be specific for intact PTH and not cross-react significantly with related substances like PTH fragments or PTHrP.	- Crossreactivity to human PTH 7-84 was determined to be equimolar in the assay. (This means it reacts equally with this fragment, which is relevant as PTH 7-84 is a known fragment. It doesn't state if this is ideal or a limitation, but it's a measured characteristic).- Crossreactivity to human PTHrP 1-40 was determined to not cross react in the assay. (This indicates good specificity against PTHrP).
No Change in Technology: The core assay methodology should remain consistent with the predicate device.	- There is no change in technology from the original device cleared under K962598.

2. Sample size used for the test set and the data provenance

The document does not provide specific sample sizes
for the studies conducted. It only generally describes the types of comparisons made (e.g., 6 different blood collection tubes).

Data provenance (e.g., country of origin, retrospective/prospective) is also not specified in the provided text.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This type of information is generally not applicable to an immunoassay 510(k) submission focused on analytical performance and substantial equivalence. Ground truth for an immunoassay is typically established via reference methods or clinical samples with confirmed conditions, not expert consensus on image interpretation. The document does not mention any expert review or qualification for establishing "ground truth."

4. Adjudication method for the test set

Not applicable, as there's no mention of expert review or adjudication.

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

This is not applicable to an immunoassay for quantitative measurement of a biomarker. MRMC studies are relevant for imaging devices or AI tools that assist human readers in interpretation.

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

This is not applicable. The device is an immunoassay, which is a standalone diagnostic test performed in a lab, generating a numerical result. It doesn't involve an "algorithm only" component in the sense an AI diagnostic tool would, nor does it typically involve a "human-in-the-loop" for interpreting its direct output in the same way an imaging AI would. The human (clinician) interprets the results of the test in conjunction with other clinical data.

7. The type of ground truth used

For an immunoassay, "ground truth" for demonstrating analytical performance typically involves:

Reference standards/calibrators: For accuracy, linearity, and precision.
Spiked samples: To assess recovery and interference.
Clinical samples with established diagnoses: To assess clinical performance (though this document focuses on analytical equivalence, not a new clinical claim).

The document details analytical comparisons, but does not explicitly state the "ground truth" methodology for specific analytical parameters. For cross-reactivity, it appears to use purified substances (human PTH 7-84, human PTHrP 1-40). For blood tube comparisons and specimen stability, the ground truth would be the results obtained from a reference or established method/tube, against which others are compared.

8. The sample size for the training set

This is not applicable to an immunoassay device, which is not an AI/machine learning algorithm requiring a "training set."

9. How the ground truth for the training set was established

This is not applicable for the same reason as #8.

Summary

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510(k) Summary 11.0

This summary of safety and effectiveness is being submitted in accordance with the requirement: of SMDA 1990 and 21 CFR 807.92.

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

Nichols Institute Diagnostics 1311 Calle Batido San Clemente, CA 92673 Phone: 949-940-7260 FAX: 949-940-7313 Contact Person: Jimmy Wong, Manager of Clinical and Technical Affairs Date Prepared: March 25, 2004

2. Device Name:

Trade/Proprietary Name:	Nichols Advantage® Chemiluminescence Intact ParathyroidHormone
Common Name:	Radioimmunoassay, Parathyroid Hormone
Classification Name:	Parathyroid hormone test system
3. Classification:	Class IIRegulation Number: 862.1545Product Code: CEW, Clinical Chemistry
Predicate Device:	Nichols Advantage Chemiluminescence Intact ParathyroidHormone

Device Description: 4.

The Nichols Advantage Intact PTH assay contains sufficient reagents for 100 tests. The assay is a two-site chemiluminometric assay specific for Intact PTH.

Indications for Use: 5.

"The Nichols Advantage® Chemiluminescence Intact Parathyroid Hormone Immunoassay is intended for use with the Nichols Advantage Specialty System for the quantitative determination of intact 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 intact parathyroid hormone levels 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."

6. Comparison to Predicate Device:

Heparinized plasma was added to the specimen matrix for Intact PTH testing. .
Use of 6 different blood collection tubes was compared for similarities and differences for . Intact PTH testing, and results of comparative testing yield essentially equivalent results.
Specimen stabilities have been included in the new labeling for EDTA plasma, . Heparinized plasma, and serum testing.
New labeling and scientific references supporting use of Intact PTH testing in patients . with chronic kidney diseases were added.

7. Similarities:

There is no change in technology from the original device cleared under K962598. .

Additional Performance Characteristics 8.

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Crossreactivity to human PTH 7-84 was determined to be equimolar in the assay. .
Crossreactivity to human PTHrP 1-40 was determined to not cross react in the assay. .

Conclusions: The device with modified labeling is substantially equivalent to the predicate device.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three curved lines representing its wings, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged in a circle around the eagle. The logo is black and white.

Public Health Service

Food and Drug Administratio 2098 Gaither Road Rockville MD 20850

JUN = 8 2004

Mr. Jimmy Wong Manager, Clinical and Technical Affairs Nichols Institute Diagnostics 1311 Calle Batido San Clemente, California 92673

K040813 Re:

K040013
Trade/Device Name: Nichols Advantage Chemiluminescence Intact Parathyroid Hormone Regulation Number: 21 CFR 862.1545 Regulation Name: Parathyroid hormone test system Regulatory Class: Class II Product Code: CEW Dated: March 20, 2004 Received: March 30, 2004

Dear Mr. Wong:

We have reviewed your Section 510(k) premarket notification of intent to market the device we have reviewed your becaren by (a) the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use sured in the May 28, 1976, the enactment date of the Medical Device Amendments, or to commerce pror to they 2011-11-11 in accordance with the provisions of the Federal Food, Drug, de necs that have been that do not require approval of a premarket approval application (PMA). and Coometier fore, market the device, subject to the general controls provisions of the Act. The r ou may, dicrerers, mains 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 it may be subject to bach additions (CFR), Parts 800 to 895. In addition, FDA 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 1 Icase oc advised that I Driv issualite or our device complies with other requirements of the Act that I Dr has intact and regulations administered by other Federal agencies. You must or any I catal statutes and sequirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

This letter will allow you to begin marketing your device as described in your Section 510(k) I his letter will anow you to oogin maketag your courselence of your dever to a legally premarket nothleation: "The PDA misms of basification 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, of If you desire specific information about and approvince of your device, please contact the Office of of questions on the promionon and Safety at (301) 594-3084. Also, please note the In Viro Diagnostic Device Evanances and season ... ... ... ... ... ... ... ... ... ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . regulation entitied, "Wilsonanaing of responsibilities under the Act from the You may of amall 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

510(k) Number (if known): K040813

Device Name: Nichols Advantage Chemiluminescence Intact Parathyroid Hormone

Indications For Use:

The Nichols Advantage® Chemiluminescence Intact Parathyroid Hormone The Nichols Advantage Shemilaninessenos intact Partially System for the immunuassay is intended for ass internethyroid hormone in human EDTA plasma, quantitative uctermination of intast psucements of parathyroid hormone levels are used nepannized plasma and soram mercalcemia (abnormally high levels of calcium in the in the unlerential diagnolo of hyporoulow.levels of calcium in the blood) resulting from blood) and flypodioomia (abhermants of intact parathyroid hormone levels disorucis or odicially and in monitoring therapeutic intervention of secondary are also used an an all infinently occurs in chronic kidney disease. Assay results nypelparathyroldent that took with other clinical data to assist the clinician in making individual patient management decisions.

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use __ (21 CFR 807 Subpart C)

(Please Do NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Alberto Cals

Division Sign-

Office of In Vitro Diagnos Device Evaluation and S

510(k) K040813

Page 1 of

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.