The ASI Automated RPR (rapid plasma reagin) Test for Syphilis, for use on the ASI Evolution Automated Syphilis Analyzer, is a qualitative and semi-quantitative nontreponemal flocculation test for the detection of reagin antibodies in human serum and plasma as a screening test for serological evidence of syphilis. All reactive RPR test samples should be further tested with a treponemal test. The ASI Automated RPR Test for Syphilis is for professional use only. The test is intended to be used for in vitro diagnostic testing and blood donor screening.

The ASI Evolution is intended to be used as a fully automated analyzer to objectively interpret the results of the ASI Automated RPR Test for Syphilis. The ASI Evolution is designed to provide standardized test interpretation and to provide for storage, retrieval, and transmittal of the test results. It is intended to be acquired, possessed and used only by health care professionals. The ASI Evolution analyzer, in conjunction with the ASI Automated RPR Test for Syphilis is intended to be used for in vitro diagnostic testing and blood donor screening.

Device Description

The Automated RPR Test for Syphilis performed on the ASI Evolution is an automated nontreponemal flocculation test for the detection of reqain antibodies in human serum and plasma.

The ASI Evolution is an integrated digital particle analyzer designed to objectively interpret certain slide agglutination tests manufactured by Arlington Scientific, Inc. (ASI). The ASI Evolution fully automates the sample and reagent handling steps of the test procedure. Qualitative and semiquantitative tests are performed by laboratory professionals who use the ASI Evolution to provide standardized test interpretation using criteria that define reactive and nonreactive agglutination reactions.

The ASI Evolution employs a camera that uses light reflectance to create a highly sensitive and high-resolution image of the agglutination immunoassay. This image is then analyzed by the proprietary software algorithm to interpret the agglutination pattern.

The ASI Evolution further provides tools that enable the creation, storage, retrieval and transmittal of the test results.

The ASI Automated RPR Test for Syphilis reagents include the following:

CARBON ANTIGEN - 0.003% cardiolipin, 0.020-0.022% lecithin, 0.09% cholesterol, charcoal (activated) as visual enhancer, phosphate buffer, 0.1% sodium azide as preservative and stabilizers.

CONTROLS (REACTIVE, WEAK REACTIVE, NONREACTIVE) - Human serum or defibrinated plasma (liguid), with 0.1% sodium azide as preservative.

Reagents have two-year expiration dating from date of manufacture. The specific expiration date is located on the label on the vial.

AI/ML Overview

The provided text describes the acceptance criteria and the study that proves the device meets those criteria for the ASI Automated RPR Test for Syphilis on the ASI Evolution, specifically focusing on the semi-quantitative claim for endpoint titer determination.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
All non-reactive samples must yield non-reactive test results.	100% of non-reactive samples (160 out of 160) yielded non-reactive test results.
All reactive samples must yield test results within one dilution above or below the known titer.	100% of reactive samples yielded test results within one dilution of the known titer. (Overall agreement of 100% with a 95% C.I. for individual samples ranges from 95.49% to 100%).

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

Test Set Description: A randomized and blinded panel of 10 human serum samples with known reagin antibody endpoint titers.
Sample Size: Each of the 10 samples was tested a minimum of 80 times, for a total of 800 tests (10 samples * 80 tests/sample).
- 2 of the 10 samples were non-reactive (total 160 non-reactive tests).
- 8 of the 10 samples were reactive (total 640 reactive tests).
Data Provenance: The tests were performed in-house on at least five different days by one operator using a single ASI Evolution instrument. The origin of the human serum samples themselves (e.g., country of origin) is not explicitly stated, but they are described as having "known reagin antibody endpoint titers." The study can be considered prospective as it involved testing pre-selected samples with the device to determine its performance against established ground truth.

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

The ground truth for the 10 human serum samples (known reagin antibody endpoint titers) was "determined by the ASI RPR Card Test for Syphilis on the ASiManager-AT."
The document does not explicitly state the number or qualifications of experts used to establish the ground truth via the ASI RPR Card Test on the ASiManager-AT. It implies that this was an established method of determining titers, rather than an expert consensus process for this specific study.

4. Adjudication Method for the Test Set

None specified. The study setup describes the device's output being compared directly against the "known reagin antibody endpoint titers" established by the ASiManager-AT, implying a direct comparison rather than an adjudication process between human readers or the device.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. The provided text describes an analytical study evaluating the semi-quantitative performance (endpoint titer validation) of the automated system. It does not include an MRMC study comparing human reader performance with and without AI assistance for this specific indication.
The document mentions "Clinical performance of the ASI Automated RPR Test for Syphilis on the ASI Evolution was evaluated under K173376," but focuses on overall qualitative detection rather than human reader AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes. The described study is a standalone performance evaluation of the ASI Evolution device itself, as it automates the interpretation of the RPR test. The device's proprietary software algorithm analyzes the image and interprets the agglutination pattern to report results (Reactive, Nonreactive, endpoint titers).

7. Type of Ground Truth Used

The ground truth used was "known reagin antibody endpoint titers," which were "determined by the ASI RPR Card Test for Syphilis on the ASiManager-AT." This can be classified as a reference standard method (another established diagnostic test) rather than direct pathology or outcomes data from patients.

8. Sample Size for the Training Set

The sample size for the training set is not specified in the provided text. The document describes pre-market validation for the analytical performance and refers to previous clinical performance evaluations (K173376) for qualitative detection. It does not provide details on the data used to train the proprietary software algorithm itself.

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

As the training set size is not specified, how its ground truth was established is also not detailed in this document. It is implicitly understood that for an automated system, the training data would also require established ground truth to enable the algorithm to learn to interpret agglutination patterns, but the specifics are not provided here.

Summary

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Indications for Use

510(k) Number (if known)

Device Name

Indications for Use (Describe)

Prescription Use (Part 21 CFR 801 Subpart D)

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

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Arlington Scientific, Inc.

5.0 510(k) Summary

5.1 Preparation Date: 10/15/2018

Submitted By

David Binks MT (ASCP), MBA COO/Vice President Regulatory Affairs Arlington Scientific, Inc. 1840 North Technology Dr. Springville, UT 84663 Phone 801-489-8911 / Fax 801-489-5552

5.2 Trade Name – ASI Automated RPR Test for Syphilis/ASI Evolution
Regulation section: (21 CFR 866.3820) Treponema pallidum nontreponemal test reagents

Classification: Class II

Product Code: GMQ

Panel: Microbiology

Previous ASI Evolution Clearance – K173376

5.3 Predicate Device(s) - Gold Standard Diagnostics AIX1000 RPR Automated Test System (K150358)

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Arlington Scientific, Inc.

	Device Similarities and Differences
Item	ASI Automated RPR Test for Syphilis on theASI Evolution	Gold Standard Diagnostics AIX1000RPR Automated Test System
Intended Use	The ASI Automated RPR (rapid plasma reagin)Test for Syphilis, for use on the ASI EvolutionAutomated Syphilis Analyzer, is a qualitativeand semi-quantitative nontreponemalflocculation test for the detection of reaginantibodies in human serum and plasma as ascreening test for serological evidence ofsyphilis. All reactive RPR test samples shouldbe further tested with a treponemal test.The ASI Automated RPR Test for Syphilis is forprofessional use only. The test is intended to beused for in vitro diagnostic testing and blooddonor screening.The ASI Evolution is intended to be used as afully automated analyzer to objectively interpretthe results of the ASI Automated RPR test forSyphilis. The ASI Evolution is designed toprovide standardized test interpretation and toprovide for storage, retrieval, and transmittal ofthe test results. It is intended to be acquired,possessed and used only by health careprofessionals. The ASI Evolution analyzer, inconjunction with the ASI Automated RPR Testfor Syphilis is intended to be used for in vitrodiagnostic testing and blood donor screening.	The Gold Standard DiagnosticsAIX1000 Rapid Plasma Reagin (RPR)Automated Test System is a non-treponemal flocculation test that canqualitatively determine the presence ofreagin antibodies in human serum. Itmay be used to aid in the diagnosis ofsyphilis when used in conjunction withsupplemental treponemal laboratorytests and other clinical information.This test may also be used to detectnon-treponemal antibodies in samplesserially diluted to establish titerinformation. This test is not intendedfor screening blood or tissue donors.
TechnologyInstruments	The ASI Evolution is an integrated digitalparticle analyzer designed to objectivelyinterpret certain agglutination testsmanufactured by Arlington Scientific, Inc. (ASI).The ASI Evolution fully automates the sampleand reagent handling steps of the testprocedure. Laboratory professionals use theASI Evolution to provide standardized testinterpretation using criteria that define reactiveand nonreactive agglutination reactions.The ASI Evolution employs a camera to createa highly sensitive and high-resolution image ofthe agglutination immunoassay. This image isthen analyzed by the proprietary softwarealgorithm to interpret the agglutination pattern.The ASI Evolution further provides tools thatenable the creation, storage, retrieval andtransmittal of the test results.	The AIX1000 is a fully automatedmicrotiter plate processor that is ableto completely perform sampleprocessing steps, including dilutions,dispenses, and incubations. The AIXuses a probe-mounted camera to takehigh resolution images to providephotographic measurement andanalysis of agglutination. The AIX1000software automatically interpretscaptured well images and reports themas Non-reactive, Reactive, Invalid, orSkipped, based on a complexinterpretation algorithm.
Technology Reagents	Nontreponemal Macroscopic Flocculation Test	Same
Antigen	Cardiolipin, lecithin, and cholesterol withactivated carbon	Same
Reported Results	Reactive, Nonreactive, endpoint titers	Same
Interpretation	Automated	Same
Sample Processing	Automated	Same
Sample Type	Serum or Plasma	Serum only
Controls	Reactive, Weak Reactive, Nonreactive	Reactive, Nonreactive
Test card	48 well plastic test plate	Same
Indications for use	Used for in vitro diagnostic testing and blooddonor testing.	Used for in vitro diagnostics Testing

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5.4 Device Description - The Automated RPR Test for Syphilis performed on the ASI Evolution is an automated nontreponemal flocculation test for the detection of reqain antibodies in human serum and plasma.

The ASI Evolution further provides tools that enable the creation, storage, retrieval and transmittal of the test results.

The ASI Automated RPR Test for Syphilis reagents include the following:

CARBON ANTIGEN - 0.003% cardiolipin, 0.020-0.022% lecithin, 0.09% cholesterol, charcoal (activated) as visual enhancer, phosphate buffer, 0.1% sodium azide as preservative and stabilizers.

CONTROLS (REACTIVE, WEAK REACTIVE, NONREACTIVE) - Human serum or defibrinated plasma (liguid), with 0.1% sodium azide as preservative.

Reagents have two-year expiration dating from date of manufacture. The specific expiration date is located on the label on the vial.

Intended Use – The ASI Automated RPR (rapid plasma reagin) Test for Syphilis, for use on the ASI Evolution Automated Syphilis Analyzer, is a qualitative flocculation test for the detection of reagin antibodies in human serum and plasma as a screening test for serological evidence of syphilis. All reactive RPR test samples should be further tested with a treponemal test. The ASI Automated RPR Test for Syphilis is for professional use only. The test is intended to be used for in vitro diagnostic testing and blood donor screening.

The ASI Evolution is intended to be used as a fully automated analyzer to objectively interpret the results of the ASI Automated RPR Test for Syphilis. The ASI Evolution is designed to provide standardized test interpretation and to provide for storage, retrieval, and transmittal of the test results. It is intended to be acquired, possessed and used only by health professionals. The ASI Evolution analyzer, in conjunction with the ASI Automated RPR Test for Syphilis is intended to be used for in vitro diagnostic testing and blood donor screening.

ર્સ રે Clinical Data -

Clinical performance of the ASI Automated RPR Test for Syphilis on the ASI Evolution was evaluated under K173376. The study cohort consisted of 1068 prospective serum samples, 10 retrospective serum samples, 1003 retrospective plasma samples, 143 clinically diagnosed syphilis patients, and 250 pregnant women. For additional details and study results, please refer to the K173376 decision summary document.

5.6 Analytical Data -

Analytical studies supporting the qualitative detection of reagin antibodies in human plasma and serum by the ASI Automated RPR Test for Syphilis performed on the ASI Evolution were previously submitted and reviewed under K173376. Details pertaining to the study protocols and resulting data are available in the K173376 decision summary document. In addition to the previously conducted studies, validation testing to support the semi-quantitative claim for the determination of reagin antibody endpoint titers in human serum and plasma was performed. A description of the study protocol and a summary of the test results are provided below.

Endpoint Titer Validation

A randomized and blinded panel of 10 human serum samples with known reagin antibody endpoint titers, as determined by the ASI RPR Card Test for Syphilis on the ASiManager-AT, was tested with the ASI Automated RPR Test for Syphilis on the ASI Evolution using the semi-quantitative test procedure. The reactive samples had titers ranging from 1:1 to 1:256. Each sample panel member was tested a minimum of 80 times, in-house, on at

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Arlington Scientific, Inc.

least five different days by one operator using a single ASI Evolution instrument. To meet the acceptance criteria, all non-reactive samples were required to yield non-reactive test results, while all reactive samples were required to yield test results within one dilution above or below the known titer. The results of the semi-quantitative analysis are shown below.

Endpoint Titer Results
SampleReactivity	Non-reactive	Neat(1:1)	1:2	1:4	1:8	1:16	1:32	1:64	1:128	1:256	1:512	% Agreementwithin +/- 1titer (95% C.I.)
06127(Non-reactive)	80	0	0	0	0	0	0	0	0	0	0	100%(95.49% -100%)
N8E23(Non-reactive)	80	0	0	0	0	0	0	0	0	0	0	100%(95.49% -100%)
W6A16R(1:2)	0	7	69	4	0	0	0	0	0	0	0	100%(95.49% -100%)
W8B01R(1:2)	0	0	75	5	0	0	0	0	0	0	0	100%(95.49% -100%)
R7F01R(1:8)	0	0	0	0	76	4	0	0	0	0	0	100%(95.49% -100%)
R8B01R(1:8)	0	0	0	32	48	0	0	0	0	0	0	100%(95.49% -100%)

Table 3: Results from Endpoint Titer Validation Study

Non-reactive test results were observed for all 160 non-reactive samples. In addition, all reactive samples produced test results that were within one dilution of the known regain antibody titer for an overall percent agreement of 100%.

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Image /page/5/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and then the word "ADMINISTRATION" in a smaller font below.

November 30, 2018

Arlington Scientific, Inc. (ASI) David Binks, COO/VP Regulatory 1840 North Technology Dr. Springville, Utah 84663

Re: K182391

Trade/Device Name: ASI Automated RPR (rapid plasma reagin) Test for Syphilis ASI Evolution Automated Syphilis Analyzer Regulation Number: 21 CFR 866.3820 Regulation Name: Treponema pallidum nontreponemal test reagents Regulatory Class: Class II Product Code: GMQ, JQT Dated: September 4, 2018 Received: September 4, 2018

Dear David Binks:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

for

Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

Regulation Number and Section

§ 866.3820

Treponema pallidum nontreponemal test reagents.(a)
Identification. Treponema pallidum nontreponemal test reagents are devices that consist of antigens derived from nontreponemal sources (sources not directly associated with treponemal organisms) and control sera (standardized sera with which test results are compared) used in serological tests to identify reagin, an antibody-like agent, which is produced from the reaction of treponema microorganisms with body tissues. The identification aids in the diagnosis of syphilis caused by microorganisms belonging to the genusTreponema and provides epidemiological information on syphilis.(b)
Classification. Class II (performance standards).