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

Device Description

The calibrators are devices intended for medical purposes for use in the ARCHITECT Total T4 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. Total T4 measurements are used as an aid in the assessment of thyroid status. The calibrators are designed to be used on the ARCHITECT i System (i 2000, and i 10005R) with the ARCHITECT Total T4 Reagents. ARCHITECT Total T4 Calibrator kit contains: Calibrator A (Cal A) 1 × 4 mL, Calibrator B (Cal B) 1 × 4 mL, Calibrator C (Cal C) 1 × 4 mL, Calibrator D (Cal D) 1 × 4 mL, Calibrator E (Cal E) 1 × 4 mL, Calibrator F (Cal F) 1 × 4 mL. ARCHITECT Total T4 Calibrator A contains human serum. Preservative: Sodium Azide. ARCHITECT Total T4 Calibrators B-F contain different concentrations of T4 prepared in human serum. Preservative: Sodium Azide. The ARCHITECT Total T4 Calibrators are prepared to target the following concentrations: Calibrator A (Cal A) 0.0 ug/dL (0.0 nmol/L), Calibrator B (Cal B) 3.0 ug/dL (38.6 nmol/L), Calibrator C (Cal C) 6.0 ug/dL (77.2 nmol/L), Calibrator D (Cal D) 12.0 ug/dL (154.4 nmol/L), Calibrator E (Cal E) 18.0 ug/dL (231.7 nmol/L), Calibrator F (Cal F) 24.0 ug/dL (308.9 nmol/L).

AI/ML Overview

The provided document is a 510(k) premarket notification decision letter and summary for the ABBOTT LABORATORIES ARCHITECT Total T4 Calibrators. This document pertains to in-vitro diagnostic calibrators, which are used to establish reference points for quantitative determination of substances in human specimens. It is not about an AI/ML medical device, an imaging device, or a device that would typically involve human readers, ground truth consensus by experts, or MRMC studies in the way an AI diagnostic algorithm would.

Therefore, many of the questions asked, such as those related to AI/ML device performance, human readers, ground truth for imaging, and MRMC studies, are not applicable to this type of medical device.

However, I can extract information relevant to the acceptance criteria and study proving the device meets those criteria, specifically concerning its stability.

Here's a breakdown of the available information:

1. A table of acceptance criteria and the reported device performance:

The document describes stability studies for the calibrators. The "acceptance criteria" for these stability studies are referred to as "stability limit evaluation criteria." While the exact numerical criteria are not detailed (e.g., specific percentage deviation allowed), the document states that the results met these criteria.

Acceptance Criteria (High-Level)	Reported Device Performance
In-Use Condition (Open Vial) Stability: Results must meet the "stability limit evaluation criteria" at specified time points (1, 2, 3, 4, 6, 9, 12 months).	Results support a 12-month stability claim at 2-8°C for in-use conditions.
Intended Storage Condition (Closed Vial) Stability: Results must meet the "stability limit evaluation criteria" at specified time points (0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 months).	Results support a 14-month stability claim at 2-8°C for closed-vial conditions.
Value Assignment: Observed values must meet the manufacturer's pre-determined acceptance criteria for each new lot.	Stated that before each lot is released, "the observed values must meet the manufacture's acceptance criteria."

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

In-Use Stability Study: "In-use testing was performed using a minimum of 10 replicates each of the on-test calibrators, reference controls, and reference panel."
Closed Vial Stability Study: "three lots of test materials are stored at 2 – 8°C."
Value Assignment (Pre-release testing): "3 instruments, 1 run per instrument, 15 replicates per run."
Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be laboratory-based validation studies. They are prospective for the purpose of validating the new (6-point) calibrators.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience):

Not applicable. This is an in-vitro diagnostic calibrator, not an imaging or AI diagnostic device requiring expert consensus for ground truth. The "ground truth" (or reference values) for calibrators are established through physical/chemical methods (gravimetric methods, USP reference L-Thyroxine) and internal Abbott reference standards.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

Not applicable.

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 not an AI-assisted device for human reader improvement.

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

Not applicable. This is a physical calibrator kit, not an algorithm. The performance being evaluated is the stability and accuracy of the chemical solutions in the calibrators themselves, which are used to calibrate a lab instrument.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

The ground truth for the calibrator values themselves is established through:

Abbott internal reference standards.
Gravimetric methods using USP reference L-Thyroxine.

For the stability studies, the "ground truth" are the baseline measurements and the "stability limit evaluation criteria" against which subsequent measurements are compared.

8. The sample size for the training set:

Not applicable. This is not a machine learning device that requires a training set.

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

Not applicable.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 10, 2015

ABBOTT LABORATORIES LISA LUKOWSKI REGULATORY AFFAIRS PROJECT MANAGER 100 ABBOTT PARK ROAD, DEPT 9VA, AP8-I ABBOTT PARK IL 60064

Re: K151566

Trade/Device Name: ARCHITECT Total T4 Calibrators Regulation Number: 21 CFR 862.1150 Regulation Name: Calibrator Regulatory Class: II Product Code: JIT Dated: June 9, 2015 Received: June 10, 2015

Dear Lisa Lukowski:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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 Parts 801 and 809); 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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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Courtney

Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K151566

Device Name ARCHITECT Total T4 Calibrators

Indications for Use (Describe)

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

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary

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.

I. Applicant Name

Abbott Laboratories Dept. 9V6, AP8-1 100 Abbott Park Road Abbott Park, IL 60064

Primary contact person:

Lisa Lukowski, ADD, Regulatory Affairs Project Manager Phone: (224) 668-8849 Fax: (224) 667-4836 E-Mail: lisa.lukowski@abbott.com

Secondary contact person:

Mary Caren Murawski, Associate Director of Regulatory Affairs Phone: (224) 667-2817 Fax: (224) 667-4836 E-Mail: mary.murawski@abbott.com

Date Summary prepared: July 9, 2015

II. Device Name

Trade Name: ARCHITECT Total T4 Calibrators Device Classification: Class II Classification Name: Calibrator, Secondary Governing Regulation: 862.1150 Code: JIT

Classification Panel: Clinical Chemistry

510(k) Number: K151566

III. Predicate Device

ARCHITECT Total T4 Calibrators (K983440)

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IV. Description of the Device

The calibrators are designed to be used on the ARCHITECT i System (i 2000, and i 10005R) with the ARCHITECT Total T4 Reagents.

ARCHITECT Total T4 Calibrator kit contains:

Component	Number of Bottles × Volume
Calibrator A (Cal A)	1 × 4 mL
Calibrator B (Cal B)	1 × 4 mL
Calibrator C (Cal C)	1 × 4 mL
Calibrator D (Cal D)	1 × 4 mL
Calibrator E (Cal E)	1 × 4 mL
Calibrator F (Cal F)	1 × 4 mL

. ARCHITECT Total T4 Calibrator A contains human serum. Preservative: Sodium Azide.
. ARCHITECT Total T4 Calibrators B-F contain different concentrations of T4 prepared in human serum. Preservative: Sodium Azide.

The ARCHITECT Total T4 Calibrators are prepared to target the following concentrations:

Component	Concentration(ug/dL)	Concentration(nmol/L)
Calibrator A (Cal A)	0.0	0.0
Calibrator B (Cal B)	3.0	38.6
Calibrator C (Cal C)	6.0	77.2
Calibrator D (Cal D)	12.0	154.4
Calibrator E (Cal E)	18.0	231.7
Calibrator F (Cal F)	24.0	308.9

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Value Assignment:

The ARCHITECT Total T4 (TT4) calibrators are prepared using a stock solution and then value assigned using primary calibrators (Abbott internal reference standards prepared using USP material). The TT4 calibrator values must meet the sponsor's predetermined acceptance criteria within a set specification, determined by the manufacturer. Each new TT4 calibrator lot is value assigned prior to use. Before each lot is released, the TT 4 calibrators are run on 3 instruments, 1 run per instrument 15 replicates per run. The observed values must meet the manufacture's acceptance criteria.

V. Intended Use of the Device

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

VI. Summary of Technological Characteristics

The following table provides the similarities and differences between the candidate (ARCHITECT Total T4) and the predicate device (ARCHITECT Total T4, K983440).

Attribute	Predicate DeviceARCHITECT Total T4 Calibrators(2-Point Calibration)K983440	Candidate DeviceARCHITECT Total T4 Calibrators(6-Point Calibration)K151566
Intended Use	The ARCHITECT Total T4Calibrators are for the calibrationof the ARCHITECT i Systemwhen used for the quantitativedetermination of thyroxine (TotalT4) in human serum and plasma.	Same
Instrumentation	ARCHITECT i System ( i 2000SR,i 2000, and i 1000SR)	Same
Attribute	Predicate DeviceARCHITECT Total T4 Calibrators(2-Point Calibration)K983440	Candidate DeviceARCHITECT Total T4 Calibrators(6-Point Calibration)K151566
Total T4Calibrators	2 levels 0.0 and 18.0 µg/dL L-Thyroxine in human serum	6 levels 0.0, 3.0, 6.0, 12.0, 18.0, and 24.0 µg/dL L-Thyroxine in human serum
CalibratorComposition	Calibrator 1:Analyte: NoneDiluent: Human SerumPreservative: Sodium Azide Calibrator 2:Analyte: L-ThyroxineDiluent: Human SerumPreservative: Sodium Azide	Calibrator A:Analyte: NoneDiluent: Human SerumPreservative: Sodium Azide Calibrators B-F:Analyte: L-ThyroxineDiluent: Human SerumPreservative: Sodium Azide
Standardization	The calibrators are matched to anAbbott internal reference standard.This internal reference standard ismanufactured by gravimetricmethods using USP referenceL-Thyroxine.	Same
Storage andStability	The calibrators are stable until theexpiration date when stored andhandled as directed at 2-8°C.	The expiration date is 12 monthsfrom the date opened when storedand handled as directed. Do notexceed the lot expiration dateprinted on the bottle.The calibrators are stable until theexpiration date when stored andhandled as directed.
Preparation forUse	Ready to use	Same

Comparison of ARCHITECT Total T4 to Predicate ARCHITECT Total T4 Calibrators

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Comparison of ARCHITECT Total T4 to Predicate ARCHITECT Total T4 Calibrators

Stability Results:

Stability studies for the ARCHITECT Total T4 calibrators were performed based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP25-A.

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In-Use Condition (Open Vial):

Stability of the ARCHITECT Total T4 Calibrators was evaluated. At the baseline time point (0) and each subsequent time point (1, 2, 3, 4, 6, 9 and 12 months) the on-test calibrator vials are opened and squeezed to ensure good air exchange, then inverted and squeezed to release a minimum of 8 drops of material from each vial. The vials are then closed and stored at 2 to 8°C until the next time point. In-use testing was performed using a minimum of 10 replicates each of the on-test calibrators, reference controls, and reference panel with the designated reference reagents. The time point results were evaluated against the stability limit evaluation criteria. The results support the following stability claim for the ARCHITECT Total T4 Calibrators: 12 months at 2 - 8°C.

Intended Storage Condition (Closed Vial):

The stability for the ARCHITECT Total T4 Calibrators was evaluated using real-time stability study. For the real time stability study, three lots of test materials are stored at 2 – 8°C. Samples at time-points 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 months were tested and evaluated against the stability limit evaluation criteria. The results support the following stability claim for the ARCHITECT Total T4 Calibrators: 14 months at 2 – 8°C.

Standardization

The calibrators are matched to an Abbott internal reference standard. This internal reference standard is manufactured by gravimetric methods using USP reference L-Thyroxine.

VII. Conclusion

Substantial equivalence for the candidate device, ARCHITECT Total T4 Calibrators, is claimed to the predicate device cleared in K983440, ARCHITECT Total T4 Calibrators. The modifications to the calibrators have not changed the intended use, as described in its labeling, nor have the modifications altered the fundamental scientific technology of this device.

Regulation Number and Section

§ 862.1150 Calibrator.

(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). 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.