For the assessment of unsaturated thyroid binding proteins in serum or plasma using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems.

Device Description

The thyroid hormones triiodothyronine (T3) and thyroxine (T4) are bound primarily to thyroxine-binding globulin (TBG) and to a lesser extent thyroxine-binding prealbumin (TBPA) and albumin. The ACS:180 T Uptake assay measures the number of unoccupied binding sites on these proteins and is an indirect indicator of thyroid status.

T Uptake (TU) and total T4 are used to estimate the amount of circulating free T4. The estimate, or the Free Thyroxine Index (FTI), is a normalized measurement that remains relatively constant in healthy individuals and compensates for abnormal levels of binding proteins, which can occur in many different physical conditions.

Drugs or physical conditions that alter the patient's TBG levels or drugs that compete with endogenous T4 and T3 for protein-binding sites alter T Uptake results.

When serum contains high levels of T3 or T4, as in hyperthyroidism, fewer unoccupied binding sites are available. Conversely, in hypothyroidism, more binding sites are available.

The Chiron Diagnostics ACS:180 TUp assay is a double antibody competitive immunoassay using, chemiluminescent technology. The sample is incubated with Lite Reagent, which is composed of acridinium ester-labeled T3-BGG (bovine gamma globulin) and unlabeled T3. The unlabeled T3 in the Lite Reagent fills available thyroid-binding sites in the sample. The acridinium ester-labeled T3-BGG does not bind to the binding proteins in the sample.

The acridinium ester-labeled T3-BGG and unlabeled T3 compete for monoclonal mouse anti-T3 antibody in the Solid Phase. The monoclonal mouse anti-T3 antibody is bound to goat anti-mouse antibody, which is covalently coupled to paramagnetic particles in the Solid Phase. A greater amount of unlabeled T3 binding to the binding proteins in the sample results in more T3-BGG-acridinium ester binding to the monoclonal antibody, an indication of a higher amount of unsaturated binding proteins.

AI/ML Overview

This document describes a medical device called the "Chiron Diagnostics ACS:180 TUp," a thyroid hormone uptake test system.

Here's an analysis of the provided information according to your request:

Acceptance Criteria and Device Performance

The document does not explicitly define "acceptance criteria" for the device's performance in terms of accuracy or precision against a specific threshold. Instead, it presents performance characteristics such as:

Reference Range: Established for euthyroid individuals.
Specificity: Cross-reactivity with various compounds.
Method Comparison: Correlation with an alternate chemiluminescent method.
Precision: Within-laboratory precision (Total CV).

Given the absence of explicit acceptance criteria, the "Reported Device Performance" below summarizes the results provided for each characteristic.

Table of Acceptance Criteria and Reported Device Performance

Characteristic	Acceptance Criteria (Implicit/Explicit)	Reported Device Performance
Expected Results	Implied: To establish a reference range for euthyroid samples for TU Ratio, % TU, and FTI based on a 95% confidence interval. (No specific numerical target given for the range itself).	Euthyroid Reference Range (95% CI): - TU Ratio: 0.75 – 1.23 - % TU: 22.5 – 37.0 - FTI: 1.4 – 3.1
Specificity	Implied: Demonstrate low cross-reactivity with structurally similar compounds and non-target analytes.	Cross-reactivity: - L-thyroxine: <0.1%- 3,3',5-triiodothyroacetic acid: ~25%- 3,5-diiodothyronine: <0.1%- 3,3',5'-triiodothyronine (reverse T3): 0.6% (by weight)- 3-iodo-L-tyrosine: <0.05% (by weight)- 3,5-diiodo-L-tyrosine: <0.05% (by weight)
Method Comparison	Implied: High correlation (e.g., r > 0.95 or similar) with an established reference/predicate method.	Correlation with alternate chemiluminescent method: - T Uptake Ratio: r = 0.95- FTI: r = 0.97 (Equation: ACS:180 TUp FTI = 1.07 * (alternate method) + 0.04)
Precision (Total % CV)	Implied: Demonstrate acceptable within-laboratory precision for different sample concentrations. (No specific numerical target given for %CV, but typically <10% for diagnostic assays is considered good).	Total Precision (% CV): Ranged from 4.9% to 6.2% for three different samples, assayed 3 times in 6 assays, on each of 4 systems (n=72 for each sample) over 3 days.

Additional Information on the Study:

Sample sizes used for the test set and the data provenance:
- Expected Results (Reference Range): Serum samples from 100 apparently healthy individuals.
- Method Comparison: 245 samples with T Uptake ratios in the range of 0.57 to 1.68 and total T4 values in the range of 3.7 to 14.1 µg/dL.
- Precision: 3 samples (tested n=72 each).
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the context implies these are experimental studies conducted by the manufacturer for regulatory submission. It is reasonable to assume these were prospective studies conducted in a controlled environment.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an in vitro diagnostic assay that measures specific biochemical markers. The "ground truth" for such assays is typically established by comparing its performance against established, often predicate, methods or by demonstrating analytical accuracy and precision based on known concentrations or reference intervals.
- No human experts are mentioned as establishing ground truth for the test set in the way a radiologist would interpret an image. The "ground truth" for the TUp assay itself is defined by its ability to accurately measure the binding sites and correlate with established clinical interpretations of thyroid status. The "euthyroid" state for the reference range study would have been determined through other clinical and laboratory diagnostics, presumably by medical professionals, but their number and qualifications are not specified in this document.
Adjudication method for the test set:
- Not applicable. This is an in vitro diagnostic device, not an interpretative AI system requiring human adjudication for its outputs.
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 in vitro diagnostic assay, not an imaging device or an AI application designed to assist human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this entire study describes the standalone performance of the ACS:180 TUp assay. It is an automated chemiluminescent system designed to provide quantitative results directly from a biological sample.
The type of ground truth used:
- Expected Results: The "ground truth" for establishing the reference range was based on "100 apparently healthy individuals," implying their euthyroid status was confirmed by other clinical and laboratory means.
- Specificity & Precision: The ground truth for these analytical performance characteristics relates to the known concentrations of compounds and statistical measures of reproducibility around these concentrations.
- Method Comparison: The ground truth was effectively the "alternate chemiluminescent method" which served as the comparator.
The sample size for the training set:
- This document refers to an in vitro diagnostic device, not a machine learning or AI algorithm in the contemporary sense that would involve distinct "training" datasets for model development. As such, there is no concept of a separate "training set" for an algorithm in this context. The manufacturing process and quality control would involve internal validations and calibration, but not a "training set" as understood in AI/ML.
How the ground truth for the training set was established:
- Not applicable, as there is no specific "training set" for an AI/ML algorithm. For an IVD, the closest analogy would be calibration materials and quality controls, whose "ground truth" is established through highly accurate reference methods and certified reference materials.

Summary

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Company Confidential

K970539

Summary of Safety and Effectiveness

MAR 2 4 1997

As required by 21 CFR 807.92, the following 510(k) Summary is provided:

1. Submitters Information

Contact person:	William J. PignatoDirector of Regulatory Affairs
Address:	Chiron Diagnostics Corporation63 North StreetMedfield, MA 02052
Phone:	(508) 359-3825
Date Summary Prepared:	February 10, 1997

2. Device Information

Proprietary Name:	Chiron Diagnostics ACS:180 TUp
Common Name:	Triiodothyronine uptake test system
Device Classification:	Class 11, 21 CFR 862.1715

3. Predicate Device Information

Name:	ACS:180 TU Assay
Manufacturer:	Chiron Diagnostics Corporation (Formally CibaCorning Diagnostics Corp.)
Document Control #	K925257

4. Device Description

Drugs or physical conditions that alter the patient's TBG levels or drugs that compete with endogenous T4 and T3 for protein-binding sites alter T Uptake results.

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When serum contains high levels of T3 or T4, as in hyperthyroidism, fewer unoccupied binding sites are available. Conversely, in hypothyroidism, more binding sites are available.

5. Statement of Intended Use

For the assessment of unsaturated thyroid binding proteins in serum or plasma using the Chiron Diagnostics ACS:180® Automated Chemiluminescence Systems.

6. Summary of Technological Characteristics

6. Performance Characteristics

Expected Results

To confirm the ACS:180 TUp serum reference range, serum samples from 100 apparently healthy individuals were analyzed. Total T4 values were generated on all of these samples using the ACS:180 T4 test method. Based on a 95% confidence interval for euthyroid samples, the following reference range was established:

ClinicalCondition	TU Ratio	% TU	FTI
Euthvroid-	0.75–1.23	22.5-37.0	1.4-3.1of the property of the program and the county of the county of the county of the

As with all diagnostic assays, each laboratory should determine its own reference range(s) for the diagnostic evaluation of patient results.

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Performance Characteristics

Specificity

The specificity of the T3 antiserum used in the ACS:180 TUp assay has been determined in the ACS:180 T3 assay.

Compound	% Cross-reactivity
L-thyroxine	<0.1
3,3',5-triiodothyroacetic acid	~25
3,5-diiodothyronine	<0.1
3,3',5'-triiodothyronine (reverse T3)	0.6 (by weight)
Thyroid hormone analogues
3-iodo-L-tyrosine	<0.05 (by weight)
3,5-diiodo-L-tyrosine	<0.05 (by weight)

Method Comparison

For 245 samples with T Uptake ratios in the range of 0.57 to 1.68 (17.1 to 50.4% Uptake) and total T4 values in the range of 3.7 to 14.1 µg/dL (47.73 to 181.89 nmol/L), the correlation between the ACS:180 TUp assay and an alternate chemiluminescent method is 0.95.

The correlation of FTI values (n = 245) is described by the following equation:

ACS:180 TUp FTI = 1.07 (alternate chemiluminescent method) + 0.04 FTI Correlation coefficient (r) = 0.97

Precision

Three samples were assayed 3 times in 6 assays, on each of 4 systems (n = 72 for each sample), over a period of 3 days. Total precision (% CV) ranged from 4.9 to 6.2.

Regulation Number and Section

§ 862.1715 Triiodothyronine uptake test system.

(a)
Identification. A triiodothyronine uptake test system is a device intended to measure the total amount of binding sites available for binding thyroid hormone on the thyroxine-binding proteins, thyroid-binding globulin, thyroxine-binding prealbumin, and albumin of serum and plasma. The device provides an indirect measurement of thyrkoxine levels in serum and plasma. Measurements of triiodothyronine uptake are used in the diagnosis and treatment of thyroid disorders.(b)
Classification. Class II. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.