The ARCHITECT Free T4 (FT4) assay is a Chemiluminescent Microparticle Immunoassay (CMIA) for the quantitative determination of free thyroxine (Free T4) in human serum and plasma. The ARCHITECT Free T4 assay is to be used as an aid in the assessment of thyroid status.

The ARCHITECT Free T4 Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of free thyroxine (Free T4) in human serum and plasma when using the ARCHITECT Free T4 Reagent Kit.

The ARCHITECT Free T4 Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of free thyroxine (Free T4) in human serum and plasma when using the ARCHITECT Free T4 Reagent Kit.

Device Description

The ARCHITECT Free T4 assay is a two-step immunoassay to determine the presence of free thyroxine (Free T4) in human serum and plasma using CMIA technology with flexible assay protocols, referred to as Chemiflex.

In the first step, sample and anti-T4 coated paramagnetic microparticles are combined. Free T 4 (unbound) present in the sample binds to the anti-T4 coated microparticles. After washing. T3 acridinium labeled conjugate is added in the second step. Pre-Trigger and Trigger Solutions are then added to the reaction mixture; the resulting chemiluminescent reaction is measured as relative light units (RLUs). An inverse relationship exists between the amount of Free T4 in the sample and the RLUs detected by the ARCHITECT i optical system.

The calibrators are devices intended for medical purposes for use in the ARCHITECT Free T 4 assay test system to establish points of reference that are used in the quantitative determination of values in the measurement of substances in human specimens. Free T4 measurements are used as an aid in the assessment of thyroid status.

AI/ML Overview

This is a 510(k) summary for a medical device modification, specifically for the Abbott ARCHITECT Free T4 assay. It describes the device, its intended use, and the modifications made. The document also lists the verification and validation studies performed to demonstrate the device's performance after the modification. However, the provided text does not contain explicit "acceptance criteria" for the device's overall performance, nor does it present a study that directly "proves" the device meets such criteria in the format requested.

Instead, the document focuses on demonstrating substantial equivalence to a predicate device after a modification (changing from a 2-point to a 6-point calibration). The studies listed are typical for verifying the analytical performance of an in vitro diagnostic (IVD) device after a change, ensuring that the modified device performs comparably or better and continues to be safe and effective for its intended use.

Here's an attempt to extract the requested information based on the provided text, acknowledging that many details are not explicitly stated in the typical format of acceptance criteria and performance results:

1. Table of Acceptance Criteria and Reported Device Performance

As the document is a 510(k) summary for a modification, it describes studies conducted to demonstrate that the modified device is substantially equivalent to the predicate. Explicit, consolidated acceptance criteria with directly corresponding performance results in a single table are not provided. Instead, the document lists specific studies (e.g., Accuracy by Correlation, Limits of Blank/Detection/Quantitation, Linearity, Precision) that would have had their own internal acceptance criteria for passing.

For instance, the "Limits of Blank/Detection/Quantitation (LoB/LoD/LoQ)" are presented as device specifications, which could imply internal acceptance criteria were met during their determination.

Performance Metric	Acceptance Criteria (Inferred/Typical for IVD, Not Explicitly Stated)	Reported Device Performance (Modified Device)
Accuracy by Correlation	(Typically seeks good correlation with a reference method or predicate device, often R² > 0.95 or similar)	Study performed; specific results and criteria not detailed in this summary.
Accelerated Calibrator Stability	(Typically ensures calibrators remain stable for a specified period and conditions)	Study performed; specific results and criteria not detailed in this summary.
Real Time Calibrator Stability (In-Use)	(Typically ensures calibrators remain stable during usage life after opening)	Study performed; specific results and criteria not detailed in this summary.
Real Time Calibrator Stability (Intended Storage)	(Typically ensures calibrators remain stable for their shelf life under storage conditions)	Study performed; specific results and criteria not detailed in this summary.
Limit of Blank (LoB)	(Maximum blank measurement below which the analyte cannot be reliably detected)	0.22 ng/dL
Limit of Detection (LoD)	(Lowest analyte concentration reliably detected)	0.28 ng/dL
Limit of Quantitation (LoQ)	(Lowest analyte concentration reliably quantified with acceptable precision and accuracy)	0.4 ng/dL
Linearity	(Typically demonstrates proportional response across the measuring interval)	Study performed; specific results and criteria not detailed in this summary.
20-Day Precision (at Measuring Interval Limits)	(Typically assesses assay variability at low and high ends of the dynamic range)	Study performed; specific results and criteria not detailed in this summary.
20-Day Precision (to Verify Product Requirements)	(Typically assesses overall assay variability for various concentrations)	Study performed; specific results and criteria not detailed in this summary.
20-Day Precision (for Native Samples)	(Typically assesses assay variability using real patient samples)	Study performed; specific results and criteria not detailed in this summary.
Dynamic Range / Measuring Interval	(Range within which the assay can accurately measure the analyte)	0.4–6.0 ng/dL
Analytical Sensitivity	(Lowest concentration of analyte the method can differentiate from zero with a high probability)	Replaced by LoQ (0.4 ng/dL)

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

The document lists various verification/validation studies, but does not specify the sample sizes used for these studies. It refers to human serum and plasma being used for the determination of Free T4, implying human samples. The provenance of the data (e.g., country of origin, retrospective or prospective) is not mentioned.

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

This information is not applicable or provided in this type of document. For an in vitro diagnostic assay like Free T4, the "ground truth" for the test set values is typically established by reference methods, gravimetric methods, or highly characterized reference materials, not by expert human graders or reviewers in the way an imaging AI algorithm might use. The calibrators described are matched to an "Abbott internal reference standard" manufactured by gravimetric methods, which serves as a form of ground truth for calibration.

4. Adjudication Method for the Test Set

This is not applicable for this type of IVD device and its verification studies. Adjudication methods (like 2+1, 3+1) are typically used in clinical trials or studies where human expert consensus is needed to determine the "correct" classification or diagnosis, often in imaging or pathology. For an analytical assay, the "correct" value is determined instrumentally or by reference methods.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for AI algorithms that assist human readers (e.g., radiologists interpreting images) to quantify the improvement in human performance with AI assistance. The ARCHITECT Free T4 assay is an automated in vitro diagnostic test system, not an AI-assisted human reading device.

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

The device itself is a standalone automated diagnostic assay. The listed studies (Accuracy, Limits, Linearity, Precision) are all demonstrations of the algorithm/system's standalone performance in determining Free T4 levels. There is no human-in-the-loop component for the measurement process itself, beyond operating the instrument and interpreting the numerical result.

7. The Type of Ground Truth Used

The ground truth for the device's calibration and analytical performance is established through:

Abbott internal reference standard, which is manufactured by gravimetric methods based on Free Thyroxine calculation (FT4c) using L-Thyroxine, sodium salt pentahydrate (HPLC grade).
For precision studies, "native samples" (real patient samples) are mentioned, which would presumably be analyzed against the established calibration curve.
"Accuracy by Correlation" implies comparison to a reference method or the predicate device, which would serve as a comparative ground truth.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI algorithm. For an IVD assay, the system is "trained" by calibrators. The modified device uses a 6-point calibration (levels: 0.0, 0.5, 1.0, 2.0, 3.5, 6.0 ng/dL L-thyroxine in human serum). The number of runs or replicates used to establish the calibration curve from these 6 points is not specified.

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

The "ground truth" for the calibrators (which serve as the "training set" for the instrument's measurement curve) is established by:

Gravimetric methods using L-Thyroxine, sodium salt pentahydrate (HPLC grade) to prepare the calibrators at specific, known concentrations.
These calibrators are further "matched to an Abbott internal reference standard," which itself is manufactured and characterized by gravimetric methods. This ensures traceability and accuracy of the calibrator values.

Summary

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123379

NOV 2 7 2012

Attachment B 510(k) Summary (Summary of Safety and Effectiveness)

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Applicant Name:

Jacek Gorzowski, Regulatory Affairs Project Manager

Regulatory Affairs

Abbott Laboratories Diagnostics Division

Dept. 9VA, AP5N-2

100 Abbott Park Road

Abbott Park, IL 60064

jacek.gorzowski@abbott.com

Device Name:

Classification Name: Radioimmunoassay, Free Thyroxine

Trade Name: Abbott ARCHITECT Free T4

Common Name: Radioimmunoassay, Free Thyroxine

Governing Regulation: 862.1695

Device Classification: Class II

Classification Panel: Clinical Chemistry

Product Code: CEC/JIT/JJX

Legally marketed device to which equivalency is claimed:

K983417, Abbott ARCHITECT Free T4 (LN 7K65-01; 2-point calibration)

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Intended Use of Device:

Description of Device:

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Modification of Device:

This Special 510(k) modification of the ARCHITECT Free T4 assay consisted of changing the calibration from a 2-point calibration to a 6-point calibration.

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Similarities and Differences of Modified Device:

The table below compares the new device, ARCHITECT Free T4 (LN 7K65-02; 6-point calibration), with the predicate device, ARCHITECT Free T4 (LN 7K65-01; 2-point calibration) (K983417).

Attribute	Predicate DeviceARCHITECT Free T4(2-point calibration)LN 7K65-01, K983417	New DeviceARCHITECT Free T4(6-point calibration)LN 7K65-02
Intended Use	The ARCHITECT Free T4 (FT4)assay is a ChemiluminescentMicroparticle Immunoassay(CMIA) for the quantitativedetermination of free thyroxine(Free T4) in human serum andplasma. The ARCHITECT Free T4assay is to be used as an aid in theassessment of thyroid status.	Same
	The ARCHITECT Free T4Calibrators are for the calibration ofthe ARCHITECT i System whenused for the quantitativedetermination of free thyroxine(Free T4) in human serum andplasma when using theARCHITECT Free T4 Reagent Kit.
	The ARCHITECT Free T4 Controlsare for the verification of theaccuracy and precision of theARCHITECT i System when usedfor the quantitative determination offree thyroxine (Free T4) in humanserum and plasma when using theARCHITECT Free T4 Reagent Kit.

Instrumentation	ARCHITECT i System	Same
Attribute	Predicate DeviceARCHITECT Free T4(2-point calibration)LN 7K65-01, K983417	New DeviceARCHITECT Free T4(6-point calibration)LN 7K65-02
Assay Reagents	Microparticles: Anti-T4 (sheep)coated microparticles in TRISbuffer with sheep IgG stabilizers.Minimum concentration: 0.08%solids. Preservative: antimicrobialagent.Conjugate: T3 acridinium-labeledconjugate in MES buffer with NaCland Triton X-100 stabilizers.Minimum concentration: 0.2 ng/mL.Preservative: ProClin.	• Same
Free T4 Calibrators	• 2 levels• 0.5 and 6.0 ng/dL L-thyroxinein human serum	• 6 levels• 0.0, 0.5, 1.0, 2.0, 3.5,6.0 ng/dL L-thyroxine inhuman serum
CalibratorComposition	• Calibrators 1-2: L-thyroxine,sodium salt pentahydrate (HPLCgrade)• Calibrators 1-2: Diluent: HumanSerum• Calibrators 1-2: Preservative:Sodium Azide	• Calibrators B-F: Same• Calibrators A-F: Diluent: Same• Calibrators A-F: Preservative:Same
Standardization	The calibrators are matched to anAbbott internal reference standard.This internal reference standard ismanufactured by gravimetricmethods based on the FreeThyroxine calculation (FT4c) usingL-Thyroxine, sodium saltpentahydrate (HPLC grade), at eachconcentration, which depends on theamount of Total T4 found in theserum and the serum's T4 bindingcapacity.	Same
Calibrator Range	0.0–6.0 ng/dL	Same
Attribute	Predicate DeviceARCHITECT Free T 4(2-point calibration)LN 7K65-01, K983417	New DeviceARCHITECT Free T 4(6-point calibration)LN 7K65-02
Analytical Sensitivity	0.4 ng/dL	Analytical sensitivity replaced byLoQ.
LoBLoDLoQ	Not applicable	LoB: 0.22 ng/dLLoD: 0.28 ng/dLLoQ: 0.4 ng/dL
Dynamic Range/Measuring Interval	0.4–6.0 ng/dL	Same
ControlComposition	• Controls L, M, H: L-thyroxine,sodium salt pentahydrate (HPLCgrade)• Controls L, M, H: Diluent:Human Serum• Controls L, M, H: Preservative:Sodium Azide	• Controls L, M, H: Same• Controls L, M, H: Diluent: Same• Controls L, M, H: Preservative:Same

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Similarities and Differences of Modified Device (Continued):

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Similarities and Differences of Modified Device (Continued):

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Verification/Validation of Modification:

The nonclinical performance of the ARCHITECT Free T4 assay was demonstrated through the following studies:

. Accuracy by Correlation
. Accelerated Calibrator Stability
. Real Time Calibrator Stability - In-Use (Open Vial)
. Real Time Calibrator Stability - Intended Storage (Closed Vial)
◆ Limits of Blank/Detection/Quantitation (LoB/LoD/LoQ)
Linearity *
20-Day Precision at the Limits of the Measuring Interval .
20-Day Precision to Verify the Product Requirements •
20-Day Precision for Native Samples .

Conclusion:

Substantial equivalence for the modified device, ARCHITECT Free Ta (LN 7K65-02; 6-point calibration), is claimed to the predicate device cleared in K983417, ARCHITECT Free T4 (LN 7K65-01; 2-point calibration). The modification to the calibrators, which consisted of changing the calibration from a 2-point calibration to a 6-point calibration, has not changed the intended use, as described in the labeling, nor has it altered the fundamental scientific technology of the device.

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DEPARTMENT OF HEALTH & HUM AN SERVICES

Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized representation of a human figure embracing a globe, symbolizing the department's mission to protect the health of all Americans and provide essential human services.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

November 27, 2012

Abbott Laboratories c/o Jacek Gorzowski 100 Abbott Park Road Dept. 9VA, AP5N-2 Abbott Park, IL 60064-3500

Re: kl23379

Trade/Device Name: Abbott ARCHITECT Free T4 Regulation Number: 21 CFR 862.1695 Regulation Name: Free thyroxine test system Regulatory Class: Class II Product Code: CEC, JIT, JJX Dated: October 30, 2012 Received: November 1, 2012

Dear Jacek Gorzowski:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 - Jacek Gorzowski

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Carol C. Benson for

Courtney H. Lias, Ph.D.

Director

Division of Chemistry and Toxicology Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

k 123379 510(k) Number (if known): Device Name: Abbott ARCHITECT Free T4 Indications for Use

The ARCHITECT Free T , Calibrators are for the ARCHITECT i System when used for the quantitative determination of free thyroxine (Free T4) in human serum and plasma when using the ARCHITECT Free T4 Reagent Kit.

The ARCHITECT Free T4 Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of free Ta) in human serum and plasma when using the ARCHITECT Free T4 Reagent Kit.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Yung Chan

Division Vitro Diagnostics and Radiological Health Office of 510(k)

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.