The ARCHITECT Folate assay is a chemiluminescent microparticle Folate Binding Protein assay for the quantitative determination of folate in human serum and plasma on the ARCHITECT i System. Folate measurements are used in the diagnosis and treatment of megaloblastic anemia.
The ARCHITECT Folate Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of folate in human serum and plasma.
The ARCHITECT Folate Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of folate in human serum and plasma.

Device Description

The ARCHITECT Folate assay is a two-step assay for the quantitative determination of folate in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology. Two pre-treatment steps mediate the release of folate from endogenous folate binding protein.
In Pre-Treatment Step 1, the sample and Pre-treatment Reagent 2 (Dithiothreitol or DTT) are aspirated and dispensed into a reaction vessel (RV). In Pre-Treatment Step 2, an aliquot of sample/Pre-Treatment Reagent 2 mixture is aspirated and dispensed into a second RV. Pre-Treatment Reagent 1 (potassium hydroxide or KOH) is then added. An aliquot of the pre-treated sample is transferred into a third RV, followed by the addition of Folate Binding Protein (FBP) coated paramagnetic microparticles and assay specific diluent. Folate present in the sample binds to the FBP coated microparticles. After washing, pteroic acid-acridinium labeled conjugate is added and binds to unoccupied sites on the FBP coated microparticles. 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 folate in the sample and the RLUs detected by the ARCHITECT i optical system.

AI/ML Overview

The provided text describes a 510(k) submission for the ARCHITECT Folate assay, a medical device for quantitatively determining folate in human serum and plasma. The study conducted is a non-clinical performance comparison between the new ARCHITECT Folate assay and its predicate device, the AxSYM Folate assay.

Here's an analysis of the acceptance criteria and study as requested:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Precision	Substantially equivalent to predicate	Demonstrated substantially equivalent performance
Linearity	Substantially equivalent to predicate	Demonstrated substantially equivalent performance
Interferences	Substantially equivalent to predicate	Demonstrated substantially equivalent performance
Method Comparison	Good correlation with predicate	Correlation coefficient of 0.898 for serum samples
Bias	Understandable and attributable to standardization differences	General bias due to standardization differences (predicate uses gravimetric preparations, investigational assay standardized to WHO Serum Folate International Standard (IS) 03/178)

Note: The document states "The ARCHITECT Folate assay demonstrated substantially equivalent performance to the AxSYM Folate assay with correlation coefficients of 0.898 for serum samples." The acceptance criteria for "substantially equivalent" in areas like precision, linearity, and interferences are not explicitly quantified with numerical thresholds in the provided text. They are implied by the claim of substantial equivalence to the predicate device.

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

The document does not explicitly state the sample size used for the test set in the comparison study.

The data provenance is not specified in terms of country of origin or whether it was retrospective or prospective. It is a non-clinical performance study.

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

This information is not applicable to this type of study. The ground truth for a quantitative diagnostic assay is typically established through a reference method or standardization to an internationally recognized standard. In this case, the investigational assay was standardized to the WHO Serum Folate International Standard (IS) 03/178. Human expert consensus is not the method for establishing ground truth for quantitative laboratory tests like this.

4. Adjudication Method for the Test Set

This information is not applicable to this type of study. Adjudication methods (like 2+1 or 3+1) are typically used in studies where human readers are interpreting images or making subjective diagnoses, which is not the case for a quantitative immunoassay comparison. The comparison is likely done statistically between measured values.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is a non-clinical performance evaluation of a quantitative diagnostic assay, not an AI-assisted human reading study.

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 ARCHITECT Folate assay. The document describes the assay's mechanism and then presents its performance characteristics (precision, linearity, interferences, method comparison) against a predicate device. There is no mention of human-in-the-loop performance testing.

7. The Type of Ground Truth Used

The ground truth for the investigational assay was established by standardization to the WHO Serum Folate International Standard (IS) 03/178. For the comparison with the predicate, the predicate device's results serve as a comparative "truth," which were themselves based on gravimetric preparations of folic acid.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning. This is a traditional immunoassay device, not an AI/ML-based device. Therefore, a training set as understood in AI/ML is not applicable. The assay is "standardized" rather than "trained."

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

As explained above, there is no "training set" in the machine learning sense for this device. The assay was standardized to accurately recover WHO Serum Folate International Standard (IS) 03/178. This standardization process involves calibrating the assay's response to known concentrations of the analyte based on this international standard.

Summary

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k 092740

ARCHITECT Folate

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

MAR - 5 2010

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:

Darla Abańo, Sr. Regulatory Administrator Regulatory Affairs Abbott Laboratories Diagnostics Division Dept. 9V6 AP6C-2 100 Abbott Park Road Abbott Park, IL 60064

Device Name:

Reagents:

Classification Name: Folic acid test system Trade Name: ARCHITECT Folate Common Name: Folate Governing Regulation: 862.1295 Device Classification: Class II Classification Panel: Clinical Chemistry Product Code: CGN

Calibrators:

Classification Name: Calibrator, secondary Trade Name: ARCHITECT Folate Calibrators (A-F) Common Name: Calibrator Governing Regulation: 862.1150 Device Classification: Class II Classification Panel: Clinical Chemistry Product Code: JIT

ARCHITECT Folate 510(k) Submission revised

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Controls:

Classification Name: Quality Control Material (assayed and unassayed) Trade Name: ARCHITECT Folate Controls (Low, Medium, and High) Common Name: Control Governing Regulation: 862.1660 Device Classification: Class I Classification Panel: Clinical Chemistry Product Code: JJX

Legally marketed device to which equivalency is claimed:

Reagents predicate: AxSYM Folate (K972232) Calibrators predicate: AxSYM Folate (K972232) Controls predicate: AxSYM Folate (K972232)

Intended Use of Device:

Description of Device:

In Pre-Treatment Step 1, the sample and Pre-treatment Reagent 2 (Dithiothreitol or DTT) are aspirated and dispensed into a reaction vessel (RV). In Pre-Treatment Step 2, an aliquot of sample/Pre-Treatment Reagent 2 mixture is aspirated and

ARCHITECT Folate 510(k) Submission revised

Page 2 of 3

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dispensed into a second RV. Pre-Treatment Reagent 1 (potassium hydroxide or KOH) is then added. An aliquot of the pre-treated sample is transferred into a third RV, followed by the addition of Folate Binding Protein (FBP) coated paramagnetic microparticles and assay specific diluent. Folate present in the sample binds to the FBP coated microparticles. After washing, pteroic acid-acridinium labeled conjugate is added and binds to unoccupied sites on the FBP coated microparticles. 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 folate in the sample and the RLUs detected by the ARCHITECT i optical system.

Comparison of Technological Characteristics:

The ARCHITECT Folate assay utilizes chemiluminescent microparticle immunoassay (CMIA) technology for the quantitative determination of folate in human serum and plasma. The AxSYM Folate assay utilizes ion capture technology for the quantitative measurement of folate in human serum, plasma, and red blood cells (RBC).

Summary of Non-Clinical Performance:

The ARCHITECT Folate assay is substantially equivalent to the AxSYM Folate assay in terms of precision, linearity, interferences, and method comparison as demonstrated in the non-clinical performance data in this 510(k) submission.

The ARCHITECT Folate assay demonstrated substantially equivalent performance to the AxSYM Folate assay with correlation coefficients of 0.898 for serum samples. General bias in folate results between the two methods is due to the standardization differences listed in the Substantial Equivalence table. The predicate device utilizes standards based on gravimetric preparations of folic acid. The investigational assay has been standardized to accurately recover WHO Serum Folate International Standard.(IS) 03/178.

ARCHITECT Folate 510(k) Submission revised

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle.

Abbott Laboratories c/o Darla Abano 100 Abbott Park Rd., Dept 09V6, Bldg. AP6C-2 Abbott Park, IL 60064

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

MAR 0 5 2010

K092740 Re:

Trade Name: ARCHITECT Folate Regulation Number: 21 CFR §862.1295 Regulation Name: Folate Regulatory Class: Class II Product Codes: CGN, JIT, JJX Dated: March 3, 2010 Received: March 4, 2010

Dear Ms. Abano:

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 such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820).

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K092740

Device Name: ARCHITECT Folate

Indications for Use:

Reagents

Calibrators

The ARCHITECT Folate Calibrators are for the calibration of the ARCHITECT i System when used for the quantitative determination of folate in human serum and plasma.

Controls

The ARCHITECT Folate Controls are for the verification of the accuracy and precision of the ARCHITECT i System when used for the quantitative determination of folate in human serum and plasma.

Prescription Use X (Part 21 CFR 801 Subpart D) And/Or

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K092740

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Regulation Number and Section

§ 862.1295 Folic acid test system.

(a)
Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.(b)
Classification. Class II.