DPC's IMMULITE® Free T4 is intended for use with the IMMULITE® Automated Analyzer. It is a solid-phase, 2-step chemiluminescent enzyme immunoassay designed for the quantitative measurement of non-protein-bound thyroxine (free T4) levels in serum. It is intended strictly for in vitro use as an aid in the clinical assessment of thyroid status related to abnormality in thyroid function or simply a variation (physiological or pathological) in the carrier proteins, chief of which is thyroxine-binding globulin (TBG). This assay is useful in assessment of thyroid status due to TBG elevations typical of pregnancy, oral contraceptive use and estrogen therapy. Additionally, this test system is for use as an aid in detecting alterations in the TBG level which mask the effects of abnormal thyroid function in hypothyroid and hyperthyroid patients.

Device Description

IMMULITE® Free T4 (2-Step) is a solid-phase, Chemiluminescent enzyme immunoassay for use with the IMMULITE® Automated Immunoassay Analyzer.

AI/ML Overview

This document is a 510(k) premarket notification for the IMMULITE® Free T4 (2-Step) Reagent system. It seeks to demonstrate substantial equivalence to a predicate device, the DPC's Coat-A-Count® Free T4. As such, the study described is a method comparison study intended to show that the new device performs similarly to the already marketed predicate device, rather than establishing de novo acceptance criteria solely based on the device's intrinsic performance.

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for substantial equivalence are implicitly based on a strong correlation and agreement with the predicate device. The document does not explicitly state numerical acceptance criteria (e.g., minimum R-squared value, maximum bias). However, the results presented are intended to demonstrate that these unstated criteria were met.

Acceptance Criterion (Implicit)	Reported Device Performance
Strong linear correlation with predicate device	r = 0.946 (IMMULITE® Free T4 2-Step vs. Coat-A-Count® Free T4)
Close agreement in mean values with predicate device	Mean Values:
	IMMULITE® Free T4 2-Step: 1.6 ng/dL
	Coat-A-Count® Free T4: 1.6 ng/dL
Linear regression equation indicating minimal bias and slope close to 1	(IMMULITE® Free T4 2-Step) = 1.01 (Coat-A-Count® Free T4) - 0.02 ng/dL (Slope of 1.01 suggests very close agreement, and intercept of -0.02 suggests minimal systematic bias across the measured range for practical purposes).
Qualitative assertion of substantial equivalence	"Diagnostic Products Corporation asserts that IMMULITE® Free T4 (2-Step) is substantially equivalent to other commercially marketed free T4 assays, such as Coat-A-Count® Free T4."

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

Sample size for the test set: 172 patient samples.
Data provenance:
- Country of origin: Not explicitly stated.
- Retrospective or prospective: Not explicitly stated, but the mention of "patient samples" typically implies retrospective collection for a method comparison of this type.

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

This type of study (method comparison for an in vitro diagnostic device) does not typically involve human expert readers establishing ground truth in the way image analysis or clinical diagnosis studies do. The "ground truth" for the test set is established by the predicate device's measurement (Coat-A-Count® Free T4). Therefore, this section is not applicable in the traditional sense. The predicate device itself is considered the "expert" or reference method for comparison.

4. Adjudication method for the test set

Not applicable. As explained above, the "ground truth" is the measurement from the predicate device. There is no human adjudication process described for reconciling differences between the new device and the predicate in this context.

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 a study comparing two automated in vitro diagnostic (IVD) devices for measuring Free T4 in serum. It is not an MRMC study and does not involve AI assistance for human readers.

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

Yes, this was a standalone performance study of the IMMULITE® Free T4 (2-Step) assay. The comparison was entirely between the measurements generated by the new automated system and the measurements generated by the predicate automated system. There is no human-in-the-loop component described for the measurement process itself.

7. The type of ground truth used

The "ground truth" for this comparative study was the measurements obtained from the predicate device, DPC's Coat-A-Count® Free T4 assay. This predicate device is an established, legally marketed assay for Free T4.

8. The sample size for the training set

Not applicable. This document describes a validation study for a device. For IVD assays, "training set" is not typically a concept explicitly described in the same way as for machine learning algorithms. The device's components (reagents, analyzer system) are developed by the manufacturer, and their performance characteristics are optimized during that development process rather than being "trained" on a specific dataset in the statistical learning sense. The provided text refers to a method comparison study for showing equivalence, not a development or training phase.

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

Not applicable, as a training set in the machine learning sense is not described for this type of IVD device validation. The established reference method (Coat-A-Count® Free T4) serves as the comparator for the validation study, rather than a "ground truth" for a training set.

Summary

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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" arranged around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or other bird in flight, composed of three curved lines.

JUL 25 1997

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Edward M. Levine, Ph.D. Director of Clinical Affairs Diagnostic Products Corporation 5700 West 96th Street Los Angeles, CA 90045-5597

K971792 Re: IMMULITE® Free T4 (2-Step) Regulatory Class: II Product Code: CEC Dated: May 14, 1997 Received: May 15, 1997

Dear Dr. Levine:

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, Druq, 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 reqistration, listing of devices, qood 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 requlations 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 In addition, FDA may publish further announcements action. 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 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 (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Gutman

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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510 (k) Summary Safety and Effectiveness

JUL 2 5 1997 5971792

This summary of safety and effectiveness information has been prepared in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.

Name: Address:

Telephone Number: Facsimile Number:

Contact Person:

Date of Preparation:

Device Name Trade: Common:

Catalog Number:

Classification: CLIA Complexity Category:

Manufacturer:

Establishment Registration Number:

Substantially Equivalent Predicate Device:

Description of Device:

Intended Use of the Device:

Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045-5597

(213) 776-0180 (213) 776-0204

Edward M. Levine, Ph.D. Director of Clinical Affairs

May 14, 1997

IMMULITE® Free T4 (2-Step) Reagent system for the determination of free T4 in serum

LKFT1 (100 tests), LKFT5 (500 tests)

Class II device, 75-CEC (862.1695) Moderate, based on previous classification of analogous tests.

Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045-5597

DPC's Registration Number is 2017183

DPC's Coat-A-Count® Free T4 (K822882)

IMMULITE® Free T4 (2-Step) is a solid-phase, Chemiluminescent enzyme immunoassay for use with the IMMULITE® Automated Immunoassay Analyzer.

The IMMULITE® Free T4 (2-Step) assay is designed for the quantitative measurement of non-protein-bound thyroxine (free T4) levels in serum. It is intended strictly for in vitro use as an aid in the clinical assessment of thyroid status.

Summary and Explanation of the Test:

The principal thyroid hormone, thyroxine (T4) circulates almost entirely bound to carrier proteins, chief of which is thyroxine-binding globulin (TBG), in an equilibrium that tends to reassert itself in the face of altered levels of the carrier proteins by inducing a corresponding alteration in the total level of T4 in

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Diagnostic Products Corporation IMMULITE®Free T4 (2-Step) May 14, 1997

Summary and Explanation of the Test (continued):

circulation, while leaving the free T4 concentration level relatively unchanged. Hence, the free T4 concentration may be expected to correlate more closely than the total T4 concentration with clinical thyroid status, for an abnormal total T4 result may signify either an abnormality in thyroid function or simply a variation (physiological or pathological) in the carrier proteins.

Technological Comparison to Predicate:

DPC's IMMULITE® Free T4 (2-Step) is a solid-phase, 2-step chemiluminescent immunoassay. The solid phase, a polystyrene bead enclosed within an IMMULITE® Test Unit, is coated with a monoclonal antibody for T4.

The patient sample is introduced into the Test Unit, and incubated for approximately 30 minutes at 37°C with intermittent agitation. During this time, free T4 in the sample binds to antibody binding sites on the bead. Unbound material is then removed by a centrifugal wash.

An alkaline phosphatase-labeled triiodothyronine is introduced, and the Test Unit is incubated for approximately another 30-minute cycle. The unbound enzyme conjugate is removed by a centrifugal wash. Substrate is then added, and the Test Unit is incubated for a further 10 minutes.

The chemiluminescent substrate, a phosphate ester of adamantyl dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this intermediate results in the sustained emission of light, thus improving precision by providing a window for multiple readings. The bound complex -- and thus also the photon output, as measured by the luminometer -- is inversely proportional to the concentration of free T4 in the sample.

The IMMULITE® Free T4 (2-step) system has been optimized to leave essentially undisturbed the original equilibrium between free and protein-bound T4 in the patient sample.

The DPC's Coat-A-Count® Free T4 procedure is a solid-phase radioimmunoassay, wherein 127-labeled T4 analog competes for a fixed time with free T4 in the patient sample for sites on T4-specific antibody. Because the antibody is immobilized to the wall of a polypropylene tube, simply decanting the supernatant suffices to terminate the competition and to isolate the antibody-bound fraction of the radiolabeled free T4. Counting the tube in a gamma counter then yields a number, which converts by way of calibration curve to measure of the free T4 present in the patient sample.

The Coat-A-Count® Free T4 system has been optimized to eliminate all binding of the T4 analog tracer to endogenous proteins, while leaving essentially undisturbed the original equilibrium between free and protein-bound T4 in the patient sample. The tracer itself has no measurable affinity for thyroxin-binding globulin (TBG), the principal thyroid hormone transport protein. To prevent binding of the tracer to albumin, blocking agents are present, at a concentration carefully adjusted to avoid displacement of native T4 from endogenous carrier proteins. To further minimize the risk of "stripping", the system employs an antibody, at low concentration, with an affinity for T4 slightly less than that of TBG, and operates under physiological conditions of temperature, pH and ionic strength.

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Diagnostic Products Corporation IMMULITE® Free T4 (2-Step) May 14, 1997

Method Comparison:

The IMMULITE® Free T4 (2-Step) procedure was compared to Coat-A-Count® Free T4 assay on 172 patient samples, with free T4 concentrations ranging from approximately 0.3 to 4.8 ng/dl. Linear regression analysis yielded the following statistics:

(IMMULITE® Free T4 2-Step) = 1.01 (Coat-A-Count® Free T4) - 0.02 ng/dL r = 0.946

1.6 ng/dL (IMMULITE® Free T4 2-Step) Mean Values: 1.6 ng/dL (Coat-A-Count® Free T4)

Performance Equivalence:

Diagnostic Products Corporation asserts that IMMULITE® Free T4 (2-Step) is substantially equivalent to other commercially marketed free T4 assays, such as Coat-A-Count® Free T4. Each product is intended strictly for in vitro diagnostic use as an aid in the clinical assessment of thyroid status.

Conclusion:

The data presented in this summary of safety and effectiveness is the data that the Food and Drug Administration used in granting DPC substantial equivalence for IMMULITE® Free T4 (2-Step).

Edward L. Renie

Edward M. Levine, Ph.D. Director, Clinical Affairs

sty/ez

Date

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510(k) Number (if known):_____________________________________________________________________________________________________________________________________________________

Device Name: IMMULITE* Free T4 (2-Step) Indications For Use:

DPC's IMMULITE® Free T4 is intended for use with the IMMULITE® Automated Analyzer. It is a solid-phase, 2-step chemiluminescent enzyme immunoassay designed for the ouantitative measurement of non-protein-bound thyroxine (free T4) levels in serum. It is intended strictly for in vitro use as an aid in the clinical assessment of thyroid status related to abnormality in thyroid function or simply a variation (physiological or pathological) in the carrier proteins, chief of which is thyroxine-binding globulin (TBG). This assay is useful in assessment of thyroid status due to TBG elevations typical of pregnancy, oral contraceptive use and estrogen therapy. Additionally, this test system is for use as an aid in detecting alterations in the TBG level which mask the effects of abnormal thyroid function in hypothyroid and hyperthyroid patients.

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K971797

(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

§ 862.1695 Free thyroxine test system.

(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.