The ACCESS® Total T3 Assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of triiodothyronine levels in human serum, using the ACCESS® Immunoassay System. The clinical importance of total serum T3 determination is in the diagnosis of thyroid disorders. Elevated concentrations of T3 can be found in Grave's disease, and most other classical causes of hyperthyroidism. Decreased concentrations occur in primary hypothyroid diseases such as Hashimoto's thyroiditis and neonatal hypothyroidism or secondary hypothyroidism due to defects at the hypothalamo-hypophyseal level.

Device Description

The ACCESS® Total T3 reagents and the ACCESS® Immunoassay Analyzer comprise the ACCESS® Immunoassay System for the quantitative determination of triiodothyronine in human serum.

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Acceptance Criteria and Device Performance for ACCESS® Total T3 Assay

This submission describes the ACCESS® Total T3 assay, an in vitro diagnostic device for the quantitative determination of triiodothyronine (T3) levels in human serum. The studies presented demonstrate analytical performance, proving substantial equivalence to a predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

The documentation does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for precision, accuracy, or correlation. Instead, it presents the results of studies and implies that these results are considered acceptable for demonstrating substantial equivalence to the predicate device. For the purpose of this analysis, the reported statistical results from the "Summary of Studies" section are presented as the "reported device performance." The implied acceptance is that these values demonstrate performance comparable to or adequate for the intended use and are similar to a legally marketed predicate device.

Performance Metric	Reported Device Performance	Implied Acceptance Criteria (Based on Substantial Equivalence)
Precision
Within-run CV	3.22% CV (high control) to 5.22% CV (low control)	Clinically acceptable variability for T3 measurement; comparable to predicate.
Total Imprecision CV	4.74% CV (high control) to 9.12% CV (low control)	Clinically acceptable variability for T3 measurement over time; comparable to predicate.
Accuracy (Recovery)
Dilution Recovery	85.6% to 107.7% recovery	Within a clinically acceptable range (e.g., 80-120% or 90-110%) for T3 assays.
Spiking Recovery	87.7% to 112.1% recovery	Within a clinically acceptable range (e.g., 80-120% or 90-110%) for T3 assays.
Correlation	r = 0.978, y = 1.020x + 0.077 (vs. Ciba Corning ACS™ T3)	Strong correlation (r > 0.95) and minimal bias / proportional error (slope near 1, intercept near 0) with a predicate device.
Analytical Sensitivity	0.1 ng/ml (lowest detectable level distinguishable from zero with 95% confidence)	Clinically relevant lower limit of detection for T3, allowing for diagnosis of low T3 states.

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

Sample Size for Test Set:
- Precision Studies: Not explicitly stated for each level (low, mid, high control), but typically involves replicates over several runs/days.
- Accuracy (Recovery) Studies: "two patient samples" for dilution recovery and "two patient samples" for spiking recovery. This is a very small sample size for these studies.
- Correlation Study: 153 samples.
- Analytical Sensitivity: Not explicitly stated but usually involves multiple measurements of zero calibrator and low-level samples.
Data Provenance: The document does not specify the country of origin for the patient samples. It also does not explicitly state whether the studies were retrospective or prospective, though performance studies for a 510(k) submission are typically prospective, conducted under controlled conditions to evaluate the new device's analytical capabilities.

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

N/A. This device is an in vitro diagnostic assay for a quantitative analyte (Total T3). The "ground truth" for the test set is established by the reference measurement method (the predicate device for correlation) or by the inherent properties of the controls and spiked/diluted samples. There are no human experts involved in establishing a "ground truth" in the way one would for image interpretation or disease diagnosis.

4. Adjudication Method for the Test Set

N/A. No adjudication method is applicable as this is not a subjective interpretation task requiring expert consensus.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) and would assess the impact of an AI tool on reader performance. The ACCESS® Total T3 assay is an automated quantitative immunoassay.

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

Yes, the studies presented are essentially "standalone" performance evaluations. The device (ACCESS® Immunoassay System and reagents) outputs a quantitative T3 value, and the performance metrics (precision, accuracy, correlation, sensitivity) are evaluated based on these automated outputs. There is no human-in-the-loop component for interpreting the result itself, though human operators are involved in running the assay.

7. The Type of Ground Truth Used

Precision: Statistical variability of repeated measurements on control materials or patient samples. The "ground truth" is the inherent stability and reproducibility of the assay.
Accuracy:
- Dilution/Spiking Recovery: The "ground truth" is the expected concentration based on the known dilution factor or amount spiked.
- Correlation: The "ground truth" is the measurement obtained from the legally marketed predicate device (Ciba Corning ACS™ T3 assay).
Analytical Sensitivity: The "ground truth" is typically defined by statistical methods (e.g., 95% confidence interval of zero calibrator measurements).

8. The Sample Size for the Training Set

N/A. The ACCESS® Total T3 assay is a biochemical immunoassay, not a machine learning or AI-based algorithm that requires a "training set" in the conventional sense. The assay's performance characteristics are inherent to its chemical and biological components and the instrument's design.

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

N/A. As there is no "training set" for this type of device, this question is not applicable.

Summary

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510(k) Premarket Notification Confidential

K973966

OCT 31 1997

1. General Information

Device Generic Name: Device Trade Name: Applicant's Name and Address:

Enzyme Immunoassav, Total T3 ACCESS® Total T3 assay Beckman Instruments, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

2. Predicate Device

Ciba Corning ACS™ T3 Ciba Corning Diagnostics Corp. Medfield, MA 02052

APPENDIX 4: Summary of Safety and Effectiveness Information

3. Device Description

The ACCESS® Total T3 reagents and the ACCESS® Immunoassay Analyzer comprise the ACCESS® Immunoassay System for the quantitative determination of triiodothyronine in human serum.

4. Indications for Use

The ACCESS® Total T3 assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of trijodothyronine levels in human serum using the ACCESS® Immunoassav System.

5. Comparison of Technological Characteristics

Both the ACCESS® Total T3 assay and the Ciba Corning ACS™ T3 assay measure triiodothyronine in human serum. The ACCESS® Total T3 assay and the Ciba Corning ACS™ T3 assay are competitive binding immunoassays. Both assays utilize microparticle technology. The ACCESS® Total T3 binds streptavidin to paramagnetic particles and Ciba Corning ACS™ T3 binds T3 analogue to paramagnetic particles. Both assays use light generated from a chemiluminescent reaction which is measured in a luminometer. Both assavs use a T3 analoque and an alkaline phosphatase coniugated monoclonal anti-T3 antibody. The ACCESS® Total T3 assay uses a monoclonal anti-T3 antibody conjugated to alkaline phosphatase which acts on a dioxetane based chemiluminescent substrate to produce light. The Ciba Corning ACS™ T3 assay uses a monoclonal anti-T3 antibody coniugated to acridinium ester which when activated by hydrogen peroxide and weak sodium peroxide produces light. The ACCESS® Total T3 assay uses a six point calibration while the Ciba Corning ACS™ T3 assay uses a two point calibration. The ACCESS® Total T3 assay utilizes a T3 analogue coupled to biotin while the Ciba Corning ACS™ utilizes a T3 analoque coupled to particles.

6. Summary of Studies

Precision studies: Within run precision ranges from 3.22% CV (high control) to 5.22% CV (low control). Total imprecision ranges from 4.74% CV (high control) to 9.12% CV (low control). Accuracy: Dilution recovery studies performed by diluting two patient samples containing Total T3 with Total T3 Calibrator S0 range from 85.6% to 107.7% recovery. Spiking recovery studies performed by adding T3 to two patient samples containing low levels of T3 range from 87.7% to 112.1 % recovery.

Correlation: A comparison of Total T3 values from 153 samples run in both the ACCESS® Total T3 assay and the Ciba Corning ACS™ T3 assay gives the following statistical data using deming calculations: r = 0.978, v = 1.020x + 0.077.

Analytical Sensitivity: The lowest detectable level of total T3 distinguishable from zero (Total T3 Calibrator S0) with 95% confidence is 0.1 ng/ml.

7. Conclusion

The ACCESS® Total T3 reagents when used with the ACCESS® Immunoassay Analyzer are substantially equivalent to another test for the measurement of Total T3 commercial distribution.

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Image /page/1/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with its wings spread, with three lines representing the feathers. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The logo is simple and recognizable, and it is often used on official documents and websites related to the department.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

OCT 31 1997

Shellie Gust Requlatory Specialist Beckman Instruments, Inc. 100 Lake Hazeltine Drive Chaska, Minnesota 55318-1084

K973966 Re: Enzyme Immunoassay, Total T3 ACCESS® Total T3 Assay Regulatory Class: II Product Code: CDP, JIS Dated: October 16, 1997 October 17, 1997 Received:

Dear Ms. Gust:

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, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act 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 regulations affecting your device can be found in the Code of Federal Requlations, 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 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 Reqister. 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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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/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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INDICATIONS FOR USE STATEMENT

10(k) Number ( if known): K973966

bevice Name: ACCESS® Total T3 Reagents on the ACCESS® Immunoassay Analyzer

ndications For Use:

The ACCESS® Total T3 Assay is a paramagnetic particle, chemiluminescent immunoassay for the guantitative determination of triiodothyronine levels in human serum, using the ACCESS® mmunoassay System.

The clinical importance of total serum T3 determination is in the diagnosis of thyroid disorders. Elevated concentrations of T3 can be found in Grave's disease, and most other classical causes of hyperthyroidism. Decreased concentrations occur in primary hypothyroid diseases such as Hashimoto's thyroiditis and neonatal hypothyroidism or secondary hypothyroidism due to defects at the hypothalamo-hypophyseal level.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Clinical Laboratory
510(k) Number K973966

✓ Prescription Use

Regulation Number and Section

§ 862.1710 Total triiodothyronine test system.

(a)
Identification. A total triiodothyronine test system is a device intended to measure the hormone triiodothyronine in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases such as hyperthyroidism.(b)
Classification. Class II. This device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.