ANA line Blot is an antinuclear antibody screening test designed to identify IgG antibodies in human serum, against the following cytoplasmic and nuclear antigens, collectively in one strip: centromere, dsDNA, histones, Jo-1, Scl-70, SSA (SSA Ro52, SSA Ro60), SSB, Sm (SmB and SmD), RNP (RNP-70, RNP-A and RNP-C), and Ribosomal RNP (RPO). The test is intended as an aid in the diagnosis of autoimmune diseases such as systemic lupus erythematosus (SLE), multiple connective tissue disorders, Sjögren's syndrome, CREST syndrome, scleroderma (progressive systemic sclerosis, PSS), and myositis.

Device Description

The ANA line Blot is a clinical device designed to identify antibodies in human serum, against various cytoplasmic and nuclear antigens. This product is intended strictly for in vitro diagnostic use as an aid in the diagnosis of autoimmune diseases.

AI/ML Overview

Here's an analysis of the acceptance criteria and study detailed in the provided 510(k) summary for the ANA line Blot™:

Acceptance Criteria and Device Performance for ANA line Blot™

1. Table of Acceptance Criteria and Reported Device Performance:

The provided document does not explicitly state pre-defined acceptance criteria (e.g., target percentages for agreement). Instead, it presents the results of a method comparison study and implicitly uses the agreement with a predicate device as the benchmark for "substantial equivalence."

Metric	Acceptance Criteria (Implied)	Reported Device Performance (ANA line Blot™ vs. Predicate)
Overall Agreement	Substantial Equivalence with predicate	91%
Positive Agreement	Substantial Equivalence with predicate	92% (95% CI: 88% - 96%)
Negative Agreement	Substantial Equivalence with predicate	85% (95% CI: 73% - 93%)

2. Sample Sizes and Data Provenance:

Test Set Sample Size: 269 specimens
- 51 specimens from apparently healthy subjects (6 males, 44 females, 1 unstated; average age 49 years, range: 6-93).
- 218 specimens from autoimmune disease patients (32 males, 107 females, 79 unreported; average age 41 years, range: 10-80), including CREST syndrome, systemic lupus erythematosus (SLE), and systemic sclerosis.
Data Provenance: Not explicitly stated, but the submission is from Diagnostic Products Corporation in Los Angeles, California, and the language implies a U.S.-based study. The data is retrospective, as it involves archived specimens tested against both devices.

3. Number of Experts and Qualifications for Ground Truth: No experts were used to establish ground truth in the context of this 510(k) submission. The study compares the performance of the new device against a legally marketed predicate device, with the predicate serving as the reference for comparison, not a "ground truth" established by experts.

4. Adjudication Method: Not applicable. There was no adjudication mentioned, as the study compared two assays directly rather than interpreting outputs requiring expert consensus.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study: No, an MRMC comparative effectiveness study was not done. This study is an in vitro diagnostic device comparison, not an imaging device or human-reader study. Therefore, there is no effect size reported for human readers improving with or without AI assistance.

6. Standalone Performance: Yes, a standalone performance study was performed in the sense that the ANA line Blot™ device's performance was directly measured and compared against the predicate device using patient specimens. This isn't a "human-in-the-loop" device; its output is a direct measurement for interpretation.

7. Type of Ground Truth Used: The "ground truth" in this context is the results produced by the predicate device, the Helix Diagnostics Enzyme Immunoassay Antinuclear Antibody Screening Test. This is a common approach for 510(k) submissions seeking substantial equivalence for in vitro diagnostic devices. The intent is to show that the new device performs comparably to an already cleared device.

8. Sample Size for the Training Set: Not applicable. This document describes a method comparison study for an in vitro diagnostic assay, not a machine learning or AI-based device that typically requires a training set. The device itself (ANA line Blot™) is a laboratory test, not an algorithm that "learns."

9. How Ground Truth for Training Set was Established: Not applicable, as there is no training set for this type of device.

Summary

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JUN 0 3 2002

510(k) Summary of Safety and Effectiveness

This summary of safety and effectiveness information has been prepared in accordance with the requirements of SMDA 1990 and 21 CFR Part 807.92.

Name:	Diagnostic Products Corporation
Address:	5700 West 96th StreetLos Angeles, California 90045-5597
Telephone Number:	(310) 645-8200
Facsimile Number:	(310) 645-9999
Contact Person:	Edward M. Levine, Ph.D.Director of Clinical Affairs
Date of Preparation:	May 14, 2002
Device NameTrade:	ANA line Blot™
Catalog Number:	KALAB1 (20 tests)
Common:	An antinuclear antibody immunological test system is adevice that consists of the reagents used to measure byimmunochemical techniques the autoimmune antibodiesin serum.
Classification:	Class II device, LKJ (21CFR 866.5100)
Manufacturer:	Diagnostic Products Corporation5700 West 96th StreetLos Angeles, CA 90045(The Quality System of Diagnostic Products Corporationis registered to ISO 9001:1994)
Establishment RegistrationNumber	DPC's Registration Number 2017183
Substantially EquivalentPredicate Device:	Helix Diagnostics Enzyme Immunoassay AntinuclearAntibody Screening Test (K954723)

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Description of the Device:	The ANA line Blot is a clinical device designed toidentify antibodies in human serum, against variouscytoplasmic and nuclear antigens. This product isintended strictly for in vitro diagnostic use as an aid in thediagnosis of autoimmune diseases.
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Intended Use of the Device:

Technology Comparison:

Provided below is a comparison of DPC's ANA line Blot technology versus the Helix Diagnostics Enzyme Immunoassay Antinuclear Antibody Screening Test technology.

ANA line Blot is a line blot technique utilizing purified native and recombinant autoantigens -Centromere, DSDNA, Histones, Jo-1, Scl-70, SSA, SSB, Sm, RNP and Ribosomal RNP - that are immobilized on a nitrocellulose membrane in the form of a line. In addition, a reagent control line and a cutoff control line are also immobilized on the membrane. ANA line Blot strips are incubated with patient serum. Patient IgG binds to autoantigens immobilized on the membrane strip. Alkaline phosphatase-labeled monoclonal anti-human IgG antibodies are then incubated with the nitrocellulose membrane strip. The labeled anti-human IgG antibodies recognize patient IgG that has complexed to the autoantigens. Immune complexes are visualized by a subsequent substrate reaction.

The Helix Diagnostics Enyzme Immunoassay Antibody Screening Test is a qualitative immunoassay. Purified antigens (dsDNA, histones, SS-A/Ro, SS-B/La, Sm, SmRNP. Scl-70. Jo-1, centromere and other antigens extracted from the Hep-2 nucleus) are bound to microwells. Antibodies to these antigens, if present in diluted serum, bind in the microwells. Washing of the microwells removes unbound serum antibodies. Horseradish peroxidase (HRP) conjugated anti-human IgG immunologically binds to the bound patient antibodies forming a "conjugate - antibody - antigen" sandwich. Washing of the microwells removes unbound conjugate. An enzyme substrate in the presence of bound conjugate hydrolyzes to form a blue color. The addition of an acid stops the reaction forming a vellow end product. The intensity of the color is measured photometrically at 450nm.

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Performance Equivalence:

Diagnostic Products Corporation (DPC) asserts that the ANA line Blot produces substantially equivalent results to other commercially marketed autoimmune disease assays, such as the Helix Diagnostics Enzyme Immunoassay Antinuclear Antibody Screening Test (K954723). Both are designed to identify antibodies in human serum, against various cytoplasmic and nuclear antigens. Each product is intended strictly for in vitro diagnostic use as an aid in the diagnosis of autoimmune diseases.

Method Comparison

Two hundred and sixty-nine specimens from apparently healthy subjects and patients with different autoimmune diseases were tested by the ANAline Blot assay and by a commercially available enzyme immunoassay antinuclear antibody screening test (Kit A). These included 51 specimens from apparently healthy subjects (6 males, 44 females, and 1 unstated), with an average age of 49 years (Range: 6 - 93). Also included were 218 specimens from autoimmune disease patients (32 males, 107 females, and 79 unreported) such as CREST syndrome, systemic lupus erythematosus (SLE), and systemic sclerosis, with an average age of 41 years (Range: 10 - 80). The following results were obtained:

Image /page/2/Figure/4 description: The image shows a table comparing the results of an ANA line blot test with a helix test. The table shows the number of positive and negative results for each test. For the helix test, 16 samples were positive and 51 were negative. For the ANA line blot test, 193 samples were positive and 9 were negative. The total agreement between the two tests was 91%, the positive agreement was 92%, and the negative agreement was 85%.

95% Confidence Limits for Positive and Negative Agreements. respectively: 88% - 96%, 73% - 93%.

Conclusion:

The data presented in this summary of safety and effectiveness is the data that the Food and Drug Administration used in granting DPC substantial equivalence for the ANA line Blot.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines above and below them, resembling hair or waves.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUN 0 3 2002

Edward M. Levine, Ph.D. Director of Clinical Affairs Diagnostic Products Corporation 5700 West 96th Street Los Angeles, California 90045-5597

Re: K021257

Trade/Device Name: ANA line Blot™ Regulation Number: 21 CFR § 866.5100 Regulation Name: Antinuclear Antibody Immunological Test System Regulatory Class: II Product Code: LKJ Dated: April 18, 2002 Received: April 19, 2002

Dear Dr. Levine:

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 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); 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

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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer 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): K021257 Device Name: ANA line Blot™

Indications For Use:

ANA line Blot is an antinuclear antibody screening test designed to identify IgG antibodies in human serum, against the following cytoplasmic and nuclear antigens, collectively in one strip: centromere, dsDNA, histones, Jo-1, Sc170, SSA (SSA Ro52, SSA Ro60), SSB, Sm (SmB and SmD), RNP (RNP-70, RNP-A and RNP-C), and Ribosomal RNP (RPO). The test is intended as an aid in the diagnosis of autoimmune diseases such as systemic lupus erythematosus (SLE), multiple connective tissue disorders, Sjögren's syndrome, CREST syndrome, scleroderma (progressive systemic sclerosis, PSS), and myositis.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Sousan Saltaie

ision of Clinical Laborat

Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 866.5100 Antinuclear antibody immunological test system.

(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).