For the in vitro quantitative determination of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia.

Device Description

The ELECSYS® Parathyroid Hormone Test System is based on a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are determined usin a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code.

AI/ML Overview

The provided text describes the 510(k) submission for the ELECSYS® Parathyroid Hormone Test System. It focuses on demonstrating substantial equivalence to a predicate device rather than explicitly defining and meeting acceptance criteria through a specific study with a separate "acceptance criteria" table. However, we can infer performance criteria and reported performance from the comparison tables.

Here's an analysis based on the provided document:

Evaluation of ELECSYS® Parathyroid Hormone Test System

The submission aims to demonstrate substantial equivalence to the Nichols RIA test for Parathyroid Hormone (K954418). The "acceptance criteria" are implicitly set by the performance characteristics of the predicate device, and the ELECSYS® system attempts to match or improve upon these.

1. Table of Inferred Acceptance Criteria and Reported Device Performance

Since explicit acceptance criteria are not stated, we infer them from the performance characteristics of the predicate device. The "Reported Device Performance" refers to the ELECSYS® Parathyroid Hormone Test System's performance.

Feature	Inferred Acceptance Criteria (Based on Predicate Device)	Reported Device Performance (ELECSYS® PTH Test System)
Within-Run Precision (%CV)	3.4% at 40 pg/mL, 1.8% at 266 pg/mL	5.4% at 30.0 pg/mL, 4.0% at 62.2 pg/mL, 4.0% at 271 pg/mL, 5.8% at 44.3 pg/mL, 3.4% at 161 pg/mL, 3.9% at 702 pg/mL
Total Precision (%CV)	6.6% at 38 pg/mL, 6.1% at 277 pg/mL	5.9% at 30.0 pg/mL, 4.3% at 62.2 pg/mL, 4.3% at 271 pg/mL, 7.1% at 44.3 pg/mL, 5.0% at 161 pg/mL, 5.4% at 702 pg/mL
Analytical Sensitivity	1 pg/mL	1.20 pg/mL
Measuring Range	1.0 pg/mL - highest calibrator	1.20-5000 pg/mL (0.127-530 pmol/L)
Expected Values	10-65 pg/mL	15-65 pg/mL (1.6-6.9 pmol/L)
Limitations (Interference)	No high dose hook effect up to 100,000 pg/mL	No interference from bilirubin up to 65 mg/dL, hemoglobin up to 1.5 g/dL, intralipid up to 1500 mg/dL, biotin up to 50 ng/mL, rheumatoid factor up to 1500 U/mL, No high dose hook effect up to 17,000 U/mL
Open Vial Stability	Reconstituted - 6 weeks (2-8° C)	Open vial - 12 weeks (2-8° C)

Note: The acceptance criteria are "inferred" as the document primarily presents a comparison for substantial equivalence rather than explicitly stated, pre-defined acceptance thresholds for a new device submission. The goal is to show performance that is comparable or better than the predicate.

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

The document does not explicitly state the sample sizes used for the precision or sensitivity studies, nor does it specify the country of origin or whether the data was retrospective or prospective. It presents summary performance characteristics.

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

This information is not applicable and not provided in the document. This is an in vitro diagnostic device for quantitative determination of a biomarker, not a device requiring expert interpretation of images or clinical outcomes for ground truth establishment in the traditional sense. The "ground truth" for analytical performance (precision, sensitivity) is determined by established laboratory methods and statistical analysis.

4. Adjudication Method for the Test Set

Not applicable. As this is an in vitro diagnostic device, adjudication methods (like 2+1 reading) are typically not used for analytical performance evaluations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. An MRMC study is relevant for devices involving human interpretation of complex data (e.g., medical images). This document describes an in vitro diagnostic assay, not a device that would require an MRMC study.

6. If a Standalone (i.e. Algorithm Only Without Human-in-the-Loop Performance) Was Done

This device is a standalone assay. The performance characteristics described (precision, sensitivity, specificity, measuring range, stability) are inherent to the algorithm and chemical reagents of the ELECSYS® Parathyroid Hormone Test System itself, without a human-in-the-loop performance component beyond standard laboratory operation.

7. The Type of Ground Truth Used

For analytical performance characteristics (precision, sensitivity, measuring range, etc.), the "ground truth" is established through:

Reference Methods/Materials: Traceable to a commercially available RIA PTH test (as stated for traceability). This implies the use of validated reference standards and methods to determine absolute values or concentrations.
Statistical Analysis: Precision (within-run and total precision) is determined by running multiple samples and calculating the coefficient of variation (%CV), a statistical measure.
Spiking/Dilution Studies: Analytical sensitivity and measuring range are typically established through studies using known concentrations of the analyte.
Interference Studies: Known interfering substances are added to samples to assess their impact.

8. The Sample Size for the Training Set

This information is not provided. For an in vitro diagnostic assay, the "training set" might refer to samples used during assay development and optimization (e.g., calibrators, validation panels), but the document does not detail this. The "calibration curve" is generated on each instrument, using a 2-point calibration and a master curve provided with the reagent.

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

The document states that results are determined using a "calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code." This implies that the ground truth for calibration is established by:

Calibrators: Standard solutions with known, precisely determined concentrations of parathyroid hormone are used for the 2-point calibration. These calibrators would have their "ground truth" established through rigorous analytical methods, likely traceable to international or recognized reference standards (though specific details are not provided beyond traceability to a "commercially available RIA PTH test").
Master Curve: A predefined curve based on extensive development and validation, which corrects for lot-to-lot and instrument variations. The ground truth for this master curve would be established through a comprehensive process of characterization using a large panel of samples with reference values.

Summary

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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
Submitter name, address, contact	Roche Diagnostics Corporation9115 Hague RdIndianapolis IN 46250(317) 576 3723
	Contact person: Priscilla A Hamill
	Date prepared: August 9, 1999
Predicate device	The ELECSYS® Parathyroid Hormone Test System is equivalent to other devices legally marketed in the United States. We claim equivalence to the Nichols RIA test for Parathyroid Hormone (K954418).
Device Name	Proprietary name: ELECSYS® Parathyroid Hormone Test System
	Common name: Parathyroid Hormone Test
	Classification name: Radioimmunoassay, Parathyroid Hormone
Device description	The ELECSYS® Parathyroid Hormone Test System is based on a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection.
	Results are determined usin a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve provided with the reagent bar code.

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Intended use	For the quantitative determination of parathyroid hormone in human serumand plasma.
Indication foruse	For differential diagnosis of hypercalcemia and hypocalcemia.
Substantialequivalence	The ELECSYS® Parathyroid Hormone Test System is equivalent to otherdevices legally marketed in the United States. We claim equivalence to theNichols Intact Parathyroid Hormone (PTH) Immunoassay (K954418).
Substantialequivalence -similarities	The following table compares the ELECSYS® Parathyroid Hormone TestSystem, with the predicate device.

Feature	ELECSYS® ParathyroidHormone Test System	Predicate Device
Intended use	for the quantitativedetermination ofparathyroid hormone	for the quantitativedetermination ofparathyroid hormone
Indication for use	For differential diagnosis ofhypercalcemia andhypocalcemia.	An aid in the assessment ofcalcium metabolismdisorders.
Sample type	Human serum and plasma	Human serum and plasma

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Substantial equivalence differences

The following table compares the ELECSYS® Parathyroid Hormone Test System, with the predicate device.

Feature	ELECSYS® ParathyroidHormone Test System	Predicate Device
Assay principle	Electrochemiluminescenceimmunoassay employingthe sandwich principle.	Two-siteimmunoradiometric assay(IRMA)
Instrument	ELECSYS® 2010 and 1010Immunassay analyzers	Gamma counter
Measuring range	1.20-5000 pg/mL (0.127-530 pmol/L)	1.0pg/mL-highest calibrator
Expected values	15-65 pg/mL (1.6-6.9pmol/L)	10-65 pg/mL
Traceability	Traceable to acommercially available RIAPTH test	No information in packageinsert
Analyticalspecificity	No detection of β -CrossLaps, osteocalcin,Human PTH-fragment 1-37and bone-specific alkalinephosphatase;	No detection of HumanPTH fragments 1-34, 39-68,53-84, 44-68, and 39-84

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Substantial equivalence performance characteristics The performance characteristics of the ELECSYS® Parathyroid Hormone Test System and the predicate device are compared in the table below.

Feature	ELECSYS® ParathyroidHormone Test System	Predicate Device
Within-Runprecision (%CV)	5.4% at 30.0 pg/mL4.0% at 62.2 pg/mL4.0% at 271 pg/mL5.8% at 44.3 pg/mL3.4% at 161 pg/mL3.9% at 702 pg/mL	3.4% at 40 pg/mL1.8% at 266 pg/mL
Total precision(%CV)	5.9% at 30.0 pg/mL4.3% at 62.2 pg/mL4.3% at 271 pg/mL7.1% at 44.3 pg/mL5.0% at 161 pg/mL5.4% at 702 pg/mL	6.6% at 38 pg/mL6.1% at 277 pg/mL
Analyticalsensitivity	1.20 pg/mL	1 pg/mL

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Substantial equivalence performance characteristics, continued

The performance characteristics of the ELECSYS® Parathyroid Hormone Test System and the predicate device are compared in the table below.

Feature	ELECSYS® ParathyroidHormone Test System	Predicate Device
Limitations	No interference frombilirubin up to 65 mg/dL No interference fromhemoglobin up to 1.5 g/dL No interference fromintralipid up to 1500mg/dL No interference frombiotin up to 50 ng/mL No interference fromrheumatoid factor up to1500 U/mL No high dose hook effectup to 17,000 U/mL	No high dose hook effectup to 100,000 pg/mL
Open vialstability	Open vial - 12 weeks (2-8° C)	Reconstituted - 6 weeks(2-8° C)
On-boardstability	ELECSYS® 2010: 8 weeksELECSYS® 1010: 4 weeks(stored alternately inrefrigerator and analyzer atambient temperature 20-25 C)Up to 20 hr. opened in total	NA
Calibrationfrequency	ELECSYS® 2010:After 1 month (same lot) after 7 days - same kit ELECSYS® 1010 with every reagent kit after 7 days (20-25° C) after 3 days (25-32° C)	Assay calibrators witheach run

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three abstract human figures, possibly representing people or a family. The figures are depicted in a flowing, interconnected manner.

SEP 2 8 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Priscilla A. Hamill Regulatory Affairs, Laboratory Systems Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, Indiana 46250-0457

Re: K992680

Trade Name: ELECSYS® Parathyroid Hormone Test System Regulatory Class: II Product Code: CEW Dated: August 9, 1999 Received: August 10, 1999

Dear Ms. Hamill:

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 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). 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 requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic OS 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 (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/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

510(k) Number (if known):-NHA-

K992680

Device Name: ELECSYS® Parathyroid Hormone Test System

Indications For Use: For the in vitro quantitative determination of intact parathyroid hormone in human serum and plasma for the differential diagnosis of hypercalcemia and hypocalcemia.

San Cooper

(Division Sign Off)
Division of Clinical Laboratory Devices

1.80 K Upg 51 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)
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Over-The-Counter Use
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(Optional Format 1-2-

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.