ABBOTT ARCHITECT FOLATE by ABBOTT LABORATORIES

The Abbott ARCHITECT™ Folate assay is a Chemiluminescent Microparticle Folate Binding Protein assay for the quantitative determination of folate in human serum, plasma, and red blood cells on the Abbott ARCHITECT™ i System. Measurements obtained by this device aid in the diagnosis and treatment of megaloblastic anemia.

Device Description

The ARCHITECT Folate assay is a Chemiluminescent Microparticle Folate Binding Protein assay for the quantitative determination of folate in human serum, plasma, (tripotassium EDTA, lithium heparin, or sodium heparin) and red blood cells (tripotassium EDTA). The ARCHITECT Folate assay is calibrated with Abbott ARCHITECT Folate Calibrators. Abbott ARCHITECT Folate Controls are assayed for the verification of the accuracy and precision of the Abbott ARCHITECT™ i System.

AI/ML Overview

Here's an analysis of the provided text regarding the Abbott ARCHITECT™ Folate assay, structured to address your specific questions about acceptance criteria and study details:

Acceptance Criteria and Study Details for Abbott ARCHITECT™ Folate

The Abbott ARCHITECT™ Folate assay is a Chemiluminescent Microparticle Folate Binding Protein assay for the quantitative determination of folate. The presented study aimed to demonstrate substantial equivalence to a legally marketed predicate device, the BioRad Quantaphase II Folate Radioassay. The primary method for demonstrating this was through correlation studies using patient samples.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the statistical measures of correlation and agreement between the new device and the predicate device. While explicit "acceptance criteria" are not numerically stated beforehand (e.g., "r > 0.95"), the reported statistics (correlation coefficient, slope, and intercept with 95% confidence intervals) are the performance measures that the FDA accepted as demonstrating substantial equivalence. The FDA letter confirms the device was found substantially equivalent.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (Serum)	Reported Device Performance (Whole Blood)
Correlation Coefficient (r)	High correlation (e.g., typically >0.90 for substantial equivalence in IVD correlation studies)	0.927	0.929
Slope (Least Squares)	Close to 1 (indicating proportional agreement)	0.97 (0.92, 1.01)	1.00 (0.94, 1.06)
Intercept (Least Squares)	Close to 0 (indicating lack of constant bias)	0.44 (0.02, 0.87)	36.04 (4.62, 67.46)
Slope (Passing-Bablok)	Close to 1	1.08 (1.05, 1.12)	1.14 (1.09, 1.20)
Intercept (Passing-Bablok)	Close to 0	-0.18 (-0.47, 0.06)	-18.83 (-40.97, 3.59)

Note on Interpretation:

For the Least Squares regression, a slope of 1 and an intercept of 0 would indicate perfect agreement. The reported values for serum (slope 0.97, intercept 0.44) and whole blood (slope 1.00, intercept 36.04) are generally close to these ideals, especially considering their 95% confidence intervals.
Passing-Bablok regression is often preferred for method comparison studies as it is robust against outliers and does not assume errors only in one method. The slopes of 1.08 and 1.14, and intercepts of -0.18 and -18.83, also demonstrate good agreement, though a slight proportional and constant bias can be inferred from the deviations from 1 and 0, respectively. However, given the high correlation and the FDA's acceptance, these were deemed acceptable.

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

Sample Sizes:
- Serum: n = 333
- Whole Blood (referred to as "red blood cells" in other parts of the document): n = 160
Data Provenance: Not explicitly stated (e.g., country of origin). The study details do not specify if the data was retrospective or prospective. Given the nature of method comparison studies at the time, it's common for them to be prospective clinical samples collected for the purpose of the study.

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

N/A - This device is an in vitro diagnostic (IVD) assay for quantitative determination of a biomarker (folate). "Ground truth" is established by the analytical result of the predicate device (BioRad Quantaphase II Folate Radioassay) on the same samples, not by expert interpretation. Therefore, experts are not used in this context to establish ground truth.

4. Adjudication Method for the Test Set

N/A - Adjudication methods (like 2+1, 3+1) are relevant for studies where subjective interpretation (e.g., by radiologists) is being evaluated and discrepancies need to be resolved. This is a method comparison study for an IVD, so "adjudication" in that sense is not applicable. The comparison involves direct quantitative measurements.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This study is an analytical method comparison for an in vitro diagnostic device, not a study evaluating human reader performance with or without AI assistance.

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

Yes, in a sense, a "standalone" evaluation was performed. The ARCHITECT Folate assay (the "algorithm/device") directly measured folate levels in samples, and these results were compared to the standalone results of the predicate device. There is no human-in-the-loop component in the measurement process itself for either the new device or the predicate. The performance reported (correlation, slope, intercept) is the performance of the device itself.

7. The Type of Ground Truth Used

The "ground truth" for this method comparison study is the results obtained from the legally marketed predicate device, the BioRad Quantaphase II Folate Radioassay, on the same patient samples. This is a common approach for demonstrating substantial equivalence for new IVD devices.

8. The Sample Size for the Training Set

N/A - This is a traditional IVD method comparison study, not a machine learning model development. Therefore, there isn't a "training set" in the sense of data used to train an algorithm. The study described is entirely a validation or test set where the new device's analytical performance is compared against an established method.

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

N/A - As there is no training set in the machine learning context, this question is not applicable.

Summary

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FEB 5 1999

510(k) Summary Abbott ARCHITECT™ Folate Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

The following information as presented in the Premarket Notification [510(k)] for Abbott ARCHITECT™ Folate constitutes data supporting a substantially equivalent determination.

Substantial equivalence has been demonstrated between the ARCHITECT Folate assay and the BioRad Quantaphase II Folate Radioassay. The intended use of the ARCHITECT Folate assay is for the quantitative determination of folate in human serum, plasma, and red blood cells. The intended use of the BioRad Quantaphase II Folate Radioassay is for the quantitative determination of folate in human serum, plasma, and whole blood.

Sample	Regression Method	n	r	Slope (95%CI)	Intercept(95% CI)
Serum	Least Squares	333	0.927	0.97 (0.92, 1.01)	0.44 (0.02, 0.87)
	Passing-Bablok	333	0.927	1.08 (1.05, 1.12)	-0.18 (-0.47, 0.06)
Whole Blood	Least Squares	160	0.929	1.00 (0.94, 1.06)	36.04 (4.62, 67.46)
	Passing-Bablok	160	0.929	1.14 (1.09, 1.20)	-18.83 (-40.97, 3.59)

In conclusion, these data demonstrate that the ARCHITECT Folate assay is as safe and effective as, and is substantially equivalent to, the BioRad Quantaphase II Folate Radioassay.

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Prepared and Submitted December 1, 1998 by: Laura Granitz Senior Regulatory Specialist 1-847-938-0092

产品

Abbott Laboratories ADD Regulatory Affairs 200 Abbott Park Road Abbott Park, IL 60064-3537

CHITBCT Folats 510(k)

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Public Health Service

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FEB 5 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Laura L. Granitz Senior Regulatory Specialist ADD Regulatory Affairs Abbott Laboratories Diagnostic Division Dept. 9V6 Building AP31 200 Abbott Park Road Abbott Park, Illinois 60064

Re:	K984301
Trade Name:	Abbott ARCHITECT™ Folate
Regulatory Class:	II	Product Code:	CGN
	II		JIS
	I		JJX
Dated:	January 20, 1999
Received:	January 21, 1999

Dear Ms. Granitz:

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 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, 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 regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. 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/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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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510(k) Number (if known): 498430 l Device Name: Abbott ARCHITECT™ Folate

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluanon/(ODE)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K984301

Prescription Use
(Per 21 CFR 801.109)
(Qptional Format 1-2-96)
OR
Over-The-Counter Use__

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.