(273 days)
Not Found
Unknown
The document mentions a "proprietary software algorithm" for image analysis but does not explicitly state whether this algorithm utilizes AI or ML techniques. There is no mention of AI, DNN, or ML, nor is there a description of training or test sets in the context typically associated with ML model development.
No
This device is an in vitro diagnostic (IVD) test system used to aid in the diagnosis of syphilis by detecting reagin antibodies in human serum. It does not directly treat or prevent a disease; rather, it provides diagnostic information.
Yes
The "Intended Use / Indications for Use" states that the device "may be used to aid in the diagnosis of syphilis."
No
The device description explicitly states the system consists of RPR test reagents and the AIX1000 Agglutination Analyzer, which includes an onboard camera and hardware for delivering serum, adding antigen suspension, incubating, and shaking. This indicates the device is a system with both hardware and software components, not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the system is a "non-treponemal flocculation test that can qualitatively determine the presence of reagin antibodies in human serum." It is used "to aid in the diagnosis of syphilis." This clearly indicates that the device is intended for use in vitro (outside the body) to examine specimens (human serum) to provide information for diagnostic purposes.
- Device Description: The "Device Description" further clarifies that it is a "non-treponemal test for the qualitative determination of reagin antibodies in human serum to aid in the diagnosis of syphilis." It describes the process of analyzing serum samples with reagents and an analyzer to produce a result.
- Specimen Type: The device uses "human serum," which is a biological specimen.
- Diagnostic Purpose: The results are used "to aid in the diagnosis of syphilis."
All of these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System is a non-treponemal flocculation test that can qualitatively determine the presence of reagin antibodies in human serum. It may be used to aid in the diagnosis of syphilis when used in conjunction with supplemental treponemal laboratory tests and other clinical information. This test may also be used to detect non-treponemal antibodies in samples serially diluted to establish titer information. This test is not intended for screening blood or tissue donors.
Product codes (comma separated list FDA assigned to the subject device)
GMQ
Device Description
The Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System in a non-treponemal test for the qualitative determination of reagin antibodies in human serum to aid in the diagnosis of syphilis. This test is also used to detect non-treponemal antibodies in samples serially diluted to establish titer information. The system consists of the Gold Standard Diagnostics RPR test reagents and the Gold Standard Diagnostics AIX1000 Agglutination Analyzer. The AIX1000 Analyzer delivers serum from collection tubes into test wells. After antigen suspension is added, the test wells are then incubated while being shaken. An onboard camera creates a high resolution image. The image is then analyzed by the proprietary software algorithm to produce a result.
The RPR test reagents consist of a reactive control, a non-reactive control, and the antigen suspended in a carbon solution. When the antigen is mixed with sera, if antibodies are present, they will bind to the antigen and form black flocculants due to the presence of carbon particles. If no antibodies are present, then the carbon particles remain evenly distributed.
The antigen used in the Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System is a modified VDRL carbon antigen. The formulation is the same as that established by the Center for Disease Control (CDC) containing 0.03% cardiolipin, 0.9% cholesterol, and 0.21% lecithin.
The kit also includes untreated, 48 well reaction plates a reactive control and a non-reactive control.
Mentions image processing
An onboard camera creates a high resolution image. The image is then analyzed by the proprietary software algorithm to produce a result.
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
The retrospectively collected samples ranged in age from 10 to 98 years (mean = 35 years). Pregnant women samples ranged from 15-44 years old (median = 29 years old). HIV positive individuals ranged from 19-60 years old (median = 41 years).
Intended User / Care Setting
For Institution Use. Prescription Use.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Cross Reactivity Study:
- Sample Size: 17 different conditions (10 viral, 3 bacterial, and 4 autoimmune conditions), each tested with 10-16 individual patient samples.
- Data Source: Antibodies from serum brokers who confirmed the presence of each respective disease marker.
- Annotation Protocol: Reactive and non-reactive controls were run on each day of testing.
Interfering Substances Study:
- Sample Size: 5 samples (one non-reactive and four reactive samples with concentrations of 1:2, 1:4, 1:16, and 1:64 from four individual patients).
- Data Source: Serum broker.
- Annotation Protocol: Tested in the presence or absence of seven endogenous substances and two prescription drugs spiked in-house at specified concentrations. Qualitative (non-titer) results were recorded. Reactive and non-reactive controls were run on each day of testing.
Precision Study:
- Sample Size: Clinical samples at the following concentrations: a low RPR reactivity (
§ 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).
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized caduceus, with three human profiles forming the staff and a single serpent winding around it.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
Nov 12, 2015
Gold Standard Diagnostics Napoleon Monce Director, Product Development 2851 Spafford Street Davis, CA 95618
Re: K150358
Trade/Device Name: Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System
Regulation Number: 21 CFR 866.3820 Regulation Name: Treponema pallidum nontreponemal test reagents Regulatory Class: II Product Code: GMQ Dated: October 7, 2015 Received: October 9, 2015
Dear Mr. Monce:
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.
1
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/ResourcesforYou/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,
Tamara V. Feldblyum -S for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K150358
Device Name
The Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System
Indications for Use (Describe)
The Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System is a non-treponemal flocculation test that can qualitatively determine the presence of reagin antibodies in human serum. It may be used to aid in the diagnosis of syphilis when used in conjunction with supplemental treponemal laboratory tests and other clinical information. This test may also be used to detect non-treponemal antibodies in samples serially diluted to establish titer information. This test is not intended for screening blood or tissue donors.
Type of Use (Select one or both, as applicable)
| ☑ For Institution Use (21 CFR 601.2) | ☐ For Compassionate Use (21 CFR 601.21) |
|---|---|
| -------------------------------------------------------------------------------------- | ----------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/3/Picture/0 description: The image is a logo for Gold Standard Diagnostics. The logo is black text with a gold globe in the upper left corner. The text reads "GOLD STANDARD" in large, bold letters, with "DIAGNOSTICS" in smaller letters below. There is a small "SM" symbol in the upper right corner of the logo.
510(k) Summary
This 510(k) summary is being submitted in accordance with the requirement of SMDA 1990 and 21 CFR 807.92.
-
- Submitter's Name: Gold Standard Diagnostics 2851 Spafford St. Davis, CA. 95618 Address: Phone Number: 530-759-8000 Contact Person: Napoleon Monce Date: February 9, 2015
-
- Product and Trade Name: Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System
Common Name: Rapid Plasma Reagin (RPR) Test
Regulation Section: (21 CFR 866.3820) Treponema pallidum non-treponemal test reagents.
Classification: Class II
Product Code: GMQ
3) Legally Marketed Device to Which the Submitter Claims Equivalence:
Arlington Scientific Inc. (ASI) RPR Card Test for syphilis on the ASiManager-AT Analyzer (K111356).
4) Description of the Device:
The Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System in a non-treponemal test for the qualitative determination of reagin antibodies in human serum to aid in the diagnosis of syphilis. This test is also used to detect non-treponemal antibodies in samples serially diluted to establish titer information. The system consists of the Gold Standard Diagnostics RPR test reagents and the Gold Standard Diagnostics AIX1000 Agglutination Analyzer. The AIX1000 Analyzer delivers serum from collection tubes into test wells. After antigen suspension is added, the test wells are then incubated while being shaken. An onboard camera creates a high resolution image. The image is then analyzed by the proprietary software algorithm to produce a result.
4
The RPR test reagents consist of a reactive control, a non-reactive control, and the antigen suspended in a carbon solution. When the antigen is mixed with sera, if antibodies are present, they will bind to the antigen and form black flocculants due to the presence of carbon particles. If no antibodies are present, then the carbon particles remain evenly distributed.
The antigen used in the Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System is a modified VDRL carbon antigen. The formulation is the same as that established by the Center for Disease Control (CDC) containing 0.03% cardiolipin, 0.9% cholesterol, and 0.21% lecithin.
The kit also includes untreated, 48 well reaction plates a reactive control and a non-reactive control.
1 Kennedy, E.J. and Creighton, E.T. Venereal Disease Research Laboratory (VDRL) Slide Test. Syphilis Manual, Chapter 8. 1998. http://www.cdc.gov/std/syphilis/manual-1998/CHAPT8.pdf
5) Intended Use of the Device:
The Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System is a non-treponemal flocculation test that can qualitatively determine the presence of reagin antibodies in human serum. It may be used to aid in the diagnosis of syphilis when used in conjunction with supplemental treponemal laboratory tests and other clinical information. This test may also be used to detect non-treponemal antibodies in samples serially diluted to establish titer information. This test is not intended for screening blood or tissue donors.
6) Comparison with the Predicate Device:
The tables below provide a comparison of the Gold Standard Diagnostics (GSD) AIX1000 Rapid Plasma Reagin (RPR) Automated Test System (subject device: K150358) with the Arlington Scientific Inc. (ASI) PRP Card Test for syphilis on the ASiManager-AT Analyzer (predicate device: K111356).
| Similarities | ||
|---|---|---|
| Item | Subject Device: Gold Standard | |
| Diagnostics AIX1000 Rapid Plasma | ||
| Reagin (RPR) Automated Test | ||
| System (K150358) | Predicate Device: ASI | |
| RPR Card Test for syphilis | ||
| on the ASiManager-AT | ||
| Analyzer (K111356) | ||
| Intended Use | The Gold Standard Diagnostics AIX1000 | |
| Rapid Plasma Reagin (RPR) Automated | ||
| Test System is a non-treponemal | ||
| flocculation test that can qualitatively | ||
| determine the presence of reagin | ||
| antibodies in human serum. It may be | ||
| used to aid in the diagnosis of syphilis | ||
| when used in conjunction with | ||
| supplemental treponemal laboratory tests | ||
| and other clinical information. This test | ||
| may also be used to detect non- | The ASiManger-AT is intended | |
| to be used as an integrated | ||
| digital particle analyzer to | ||
| objectively interpret the ASI | ||
| RPR Card Test for syphilis. The | ||
| ASiManger-AT is designed to | ||
| provide standardized test | ||
| interpretation, an initial | ||
| predictive titer analysis, and | ||
| provides for storage, retrieval | ||
| and transmittal of the test |
5
| | treponemal antibodies in samples serially
diluted to establish titer information. This
test is not intended for screening blood or
tissue donors. | results. It is intended to be
acquired, possessed and used
only by healthcare
professionals. For in vitro
Diagnostic Use Only, not
intended for screening blood
and tissue donors. |
|------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Assay Format | Reports qualitative results and titer of
non-treponemal antibodies in serially
diluted samples | Same |
| Technology | Flocculation test | Same |
| Antigen | Modified VDRL carbon antigen | Same |
| Reported Results | Reactive, non-reactive, titer results | Same |
| Interpretation | Automated | Same |
| Differences | |||
|---|---|---|---|
| Item | Subject Device: Gold Standard | ||
| Diagnostics AIX1000 Rapid Plasma | |||
| Reagin (RPR) Automated Test | |||
| System (K150358) | Predicate Device: ASI RPR | ||
| Card Test for syphilis on | |||
| the ASiManager-AT | |||
| Analyzer (K111356) | |||
| Sample | |||
| Processing | Automated | Manual | |
| Sample Matrix | Serum | Serum or Plasma | |
| Controls | Reactive and non-reactive | Reactive, weak reactive, non- | |
| reactive |
6(b1): Nonclinical Studies:
Cross Reactivity
The study was conducted to evaluate potential cross reactivity from different disease conditions. A panel of antibodies from 17 different conditions (10 viral, 3 bacterial, and 4 autoimmune conditions) was obtained from serum brokers who confirmed the presence of each respective disease marker. The samples were tested on the GSD AIX1000 RPR Automated Test System. Each condition tested 10-16 individual patient samples. Reactive and non-reactive controls were run on each day of testing. The results are summarized below:
| Number | Number | |
|---|---|---|
| Positive For | Tested | Reactive |
| Rubella | 10 | 0 |
| Vericella Zoster Virus (VZV) | 10 | 0 |
| Human Immunodeficiency Virus (HIV) | 10 | 0 |
| Hepatitis B | 16 | 0 |
| Hepatitis C | 11 | O |
6
| Epstein Barr Virus (EBV) | 10 | 0 |
|---|---|---|
| Herpes Simplex Virus (HSV) Type 1 | 10 | 0 |
| Herpes Simplex Virus (HSV) Type 2 | 10 | 0 |
| Cytomegalovirus (CMV) | 11 | 0 |
| Heterophile antibodies* | 10 | 0 |
| Toxoplasma gondii | 10 | 0 |
| Leptospira biflexa | 10 | 0 |
| Borrelia burgdorferi | 10 | 0 |
| Systemic Lupus Erythematosus (SLE) | 10 | 0 |
| Rheumatoid Arthritis | 10 | 0 |
| Scleroderma | 10 | 0 |
| Primary Anti-phospholipid Syndrome | 16 | 0 |
"Heterophiles samples were tested for infectious mononucleosis (EBV and un-related non-EBV heterophile antibodies).
Interfering Substances
The effect of potential interfering substances on samples using the GSD AIX1000 RPR Automated The panel consisted of seven endogenous substances and two Test System was evaluated. prescription drugs that could be used to treat syphilis patients. Five samples, one non-reactive and four reactive samples (with a concentration of 1:2, 1:4, 1:16, and 1:64 from four individual patients), were obtained from a serum broker and were tested in the presence (interferents spiked in-house at the concentration described below) or absence of interferents. The qualitative (non-titer) result was recorded for each sample. The concentrations selected were recommended in the Clinical and Laboratory Standards Institute standard document CLSI EP7-A2. Reactive and non-reactive controls were run on each day of testing. For all substances, the RPR samples remained positive, therefore the tested substances did not affect the performance of the GSD AIX1000 RPR Automated Test System.
| Substance | Concentration | Interference |
|---|---|---|
| Hemoglobin | 20 g/dL | None Observed |
| Bilirubin (unconjugated) | 15 mg/dL | None Observed |
| Cholesterol | 250 mg/dL | None Observed |
| Albumin | 5 g/dL | None Observed |
| Gamma Globulin | 60 mg/dL | None Observed |
| Glucose | 120 mg/dL | None Observed |
| Triglyceride | 500 mg/dL | None Observed |
| Antibiotic (Cephalexin) | 337 umol/L | None Observed |
| Antibiotic (Tetracycline) | 34 umol/L | None Observed |
Precision
To test the precision of the GSD AIX1000 RPR Automated Test System, a within-lab precision study This study was conducted in-house with clinical samples at the following was conducted. concentrations: a low RPR reactivity (1:256 | % Agreement
within ± 1 titer
(95% C.I.) |
|----------------------------------|------------------|------|-----|-----|-----|------|------|------|-------|--------|-----------------------------------------------|
| Non-
Reactive
Serum | રત | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 100%
(94.5% - 100%) |
| Low RPR
Reactivity
(1:4) | 0 | 0 | 0 | 23 | 31 | 0 | 0 | 0 | 0 | 0 | 100%
(94.5% - 100%) |
| Moderately
Reactive
(1:16) | 0 | 0 | 0 | 0 | 7 | 42 | 5 | 0 | 0 | 0 | 100%
(94.5% - 100%) |
| Reactive
(1:64) | 0 | 0 | 0 | 0 | 0 | 0 | 42 | 12 | 0 | 0 | 100%
(94.5% - 100%) |
| Highly
Reactive
(1:128) | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 28 | 20 | 5 | 98.1%
(90.1% - 99.9%) |
| Reactive
control | 0 | 30 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 100%
(90.5% - 100%) |
| Non-reactive
control | 30 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 100%
(90.5% - 100%) |
The sample agreement (within ± 1 titer) for between-days, between-oays, between-operators, and between-instruments are summarized below:
9
| Sample Reactivity | Between-
Runs | Between-
Days | Between-
Operators | Between-
Instruments |
|-------------------------------|------------------|------------------|-----------------------|-------------------------|
| Non-Reactive Serum | 100% | 100% | 100% | 100% |
| Low RPR Reactivity
(1:4) | 100% | 100% | 100% | 100% |
| Moderately Reactive
(1:16) | 100% | 100% | 100% | 100% |
| Reactive
(1:64) | 100% | 97.8% | 100% | 100% |
| Highly Reactive
(1:128) | 100% | 100% | 98.1% | 100% |
Carry-over
The purpose of the carry-over study was to uncover the presence of contamination in negative specimens due to carry-over of RPR antibodies during sample processing on the GSD AIX1000 RPR Automated Test System. The study was conducted over three consecutive days on a single AIX1000 instrument. One reactive (1:64), one highly reactive (1:128) and two negative samples were tested over five runs. The samples used were from individual patients (not pooled). The qualitative (nontiter) result was recorded for each sample. Highly reactive samples were alternated with non-reactive samples (reactive 1 with non-reactive 1; reactive 1 with non-reactive 2- tested twice; reactive 2 with non-reactive 1; and reactive 2 with non-reactive 2) 96 times per run. All 480 replicates of the negative samples were reported as non-reactive, therefore, no evidence of carry-over was observed.
6(b2): Clinical Studies:
i. Prospectively Collected Samples
Prospective sample collection was conducted at two geographically distinct (Southeastern and Western United States) reference laboratories that received samples from local clinics, hospitals, and Testing was conducted at three sites (one in house and two locations that doctor's offices. represented the intended use sited for the GSD AIX1000 RPR Automated Test System. For all testing sites, reactive and non-reactive external controls were tested with the assay on each day of testing. All 765 serum samples were collected prospectively from patient samples with a physician's order to perform syphilis testing. Samples were stored frozen (-20°C) for a maximum of five months before testing. All samples that were shipped, were transported and stored frozen until testing. All three sites performed their own comparator testing.
All prospectively collected samples were "de-identified", therefore, only pregnancy and HIV status was recorded. No information regarding gender, age, syphilis stage, or antibiotic use was available.
Seven hundred sixty five (765) serum samples were tested on both the GSD RPR Automated Test System and on the comparator device (Arlington Scientific Inc. RPR Card Test for syphilis on the
10
ASiManager-AT Analyzer). The initial tests resulted in 26 invalid results (invalid rate of 3.4% with 95% CI: 2.33% - 4.93%). All 26 samples were re-tested and gave non-reactive results. The comparison of results for the prospectively collected clinical samples is summarized below:
| Prospective Samples | Comparator Device | |||
|---|---|---|---|---|
| Reactive | Non-reactive | Total | ||
| GSD AIX1000 | Reactive | 21 | 1* | 22 |
| RPR Test System | Non-reactive | 1* | 742 | 743 |
| Total | 22 | 743 | 765 |
The two discrepant samples were tested on a third FDA cleared RPR assay. Both samples were nonreactive on the third RPR assay.
The positive percent agreement and negative percent of the GSD AIX1000 RPR Automated Test System with the comparator device (along with their 95% confidence intervals) are 95.5% (C.I. 77.2% - 99.9%) and 99.9% (C.I. 99.3% - 100%), %), respectively.
To further investigate the serologic status of the non-treponemal antibody positive samples (NT+), the samples that gave a reactive result either by the GSD AIX1000 RPR Automated Test System or by the comparator device were further tested on an FDA cleared treponemal (TP) assay. Of the 21 samples that were non-treponemal antibody reactive on both the GSD AIX1000 RPR Automated Test System and on the comparator device, only 18 (18/21 = 85.7%) had enough volume for further testing; all 18 samples were positive for TP antibodies. The one sample that was NT+ on the GSD AIX1000 Automated Test System and non-treponemal non-reactive (NT-) on the comparator device was negative for TP antibodies. The one sample that was NT- on the GSD AIX1000 Automated Test System and NT+ on the comparator device was negative for TP antibodies. The 742 samples that were concordant non-reactive with the test device and the comparator device did not receive further TP testing (742/765 = 97.0%).
ii. Retrospectively Collected Samples
In addition, 2,246 retrospectively collected samples from patients referred for syphilis testing were tested on the GSD AIX1000 RPR Automated Test System and on the comparator device. The samples were obtained from sample brokers who collect from multiple sites across the United States. The samples were collected between January 2005 and July 2014 and stored at -20°C until the time of testing. Samples included 607 men and 666 women ranging in age from 10 to 98 years (mean = 35 years. The gender and age of the remaining samples were not disclosed). All samples were tested inhouse by a single operator. Reactive and non-reactive controls were tested with the assay on each day of testing. The initial tests resulted with six invalid rate of 0.27% with 95% CI: 0.12% - 0.58%). All six samples were re-tested and gave one reactive and five non-reactive results. The results are summarized below:
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| Retrospective Samples | Comparator Device | |||
|---|---|---|---|---|
| Reactive | Non-reactive | Total | ||
| GSD AIX1000 | Reactive | 556 | 15* | 571 |
| RPR Test System | Non-reactive | 16* | 1659 | 1675 |
| Total | 572 | 1674 | 2246 |
The 31 discrepant samples were tested on a third FDA cleared RPR assay. Of the 16 GSD nonreactive and comparator device reactive samples, the third RPR assay called 12 reactive and 4 nonreactive. Of the 15 GSD AIX1000 RPR Automated Test System reactive and comparator device nonreactive samples, the third RPR assay called 11 reactive and 4 non-reactive.
The positive percent agreement and negative percent of the GSD AIX1000 RPR Automated Test System with the comparator device (along with their 95% confidence intervals) are 97.2% (C.I. 95.5% - 98.4%) and 99.1% (C.I. 98.5% - 99.5%), respectively.
To further investigate the serologic status of the non-treponemal antibody positive samples (NT+), the samples that gave a reactive result either by the GSD AIX1000 RPR Automated Test System or the comparator device were further tested on an FDA cleared treponemal (TP) assay. Of the 556 samples that were non-treponemal antibody reactive on both the GSD AIX1000 RPR Automated Test System and on the comparator device, only 404 had enough volume for further TP (404/556 = 72.7%). Of the 15 samples that were NT+ on the GSD AIX1000 RPR Automated Test System and non-reactive for non-treponemal antibodies (NT-) on the comparator device, only three had enough volume for further TP testing (9/16 = 56.3%). Of the 16 samples that were NT- on the GSD AIX1000 RPR Automated Test System and NT+ on the comparator device, only nine had enough volume for further TP testing. A total of 416 samples that were reactive by either the test device or the comparator device received further TP testing. Samples that were concordant non-reactive with the test device and the comparator device did not receive further TP testing. The results are summarized below:
| | | Comparator
Device NT + /
Trep + | Comparator
Device NT + /
Trep - | Comparator
Device NT - /
Trep + | Comparator
Device NT - /
Trep - |
|--------------------------------|--------------|---------------------------------------|---------------------------------------|---------------------------------------|---------------------------------------|
| GSD AIX1000
NT Assay Result | Reactive | 366 | 38 | 1 | 2 |
| | Non-reactive | 5 | 4 | N/A* | N/A* |
*Samples with concordant non-reactive results by the comparator device and the GSD AIX1000 RPR Automated Test System did not receive further TP testing.
Three hundred thirty (330) of the retrospective collected samples were tested for titer (330/587 samples collected = 56.2%). The frequency distribution of titer results from samples that are RPR reactive on the GSD AIX1000 RPR Automated Test System is shown in the figure below:
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Image /page/12/Figure/0 description: The image is a bar graph showing the distribution of titer results. The x-axis represents the titer values, ranging from 1:1 to ≥ 1:256, while the y-axis represents the number of samples. The graph indicates that the highest number of samples have a titer of 1:2, with approximately 140 samples. The number of samples decreases as the titer increases, with the lowest number of samples having a titer of ≥ 1:256.
Distribution of Titer Results from Samples Designated as RPR Reactive on the GSD AIX1000 RPR Automated Test System.
iii. Retrospectively Collected Samples from Special Populations
Pregnant Women
In addition, 250 samples that were non-reactive for non-treponemal antibodies (NT-) were retrospectively collected from pregnant women at one site (Southeastern United States). The age of these women ranged from 15-44 years old (median = 29 years old) The samples were collected between July 2012 and August 2013 and stored at -20°C until the time of testing. To create nontreponemal antibody reactive (NT+) samples, sera from 30 individual pregnant women were collected and spiked with a pool created by combining highly reactive RPR positive samples.
Sera from 30 pregnant women were obtained and were tested on an FDA cleared Human Chorionic Gonadotropin (HCG) test to confirm the pregnancy status. All sera gave a positive HCG result. The 30 sera were then spiked with a pool of highly reactive (1:128 and 1:64) RPR positive samples. No more than 10% of the volume from the sera of pregnant women was supplanted by spiking. The spiked sera were tested again on the HCG test to confirm a positive result.
These samples were tested on the GSD AIX1000 RPR Automated Test System and on the comparator device. All samples were tested in-house by a single operator. The identity of the samples was masked. Reactive and non-reactive controls were tested with the assay on each day of testing. No invalid results were obtained. The results are summarized below:
| Pregnant Women | Comparator Device | |||
|---|---|---|---|---|
| Reactive | Non-reactive | Total | ||
| GSD AIX1000 RPR | Reactive | 30 | 0 | 30 |
| Test System | Non-reactive | 0 | 250 | 250 |
| Total | 30 | 250 | 280 |
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The positive percent agreement and negative percent of the GSD AIX1000 RPR Automated Test System with the comparator (along with their 95% confidence intervals) are 100% (C.I. 90.5% - 100%) and 100% (C.I. 98.8% - 100%), %), respectively.
HIV Positive Individuals
In addition, 250 samples that were non-reactive for non-treponemal antibodies (NT-) and 30 samples that were reactive for non-treponemal antibodies (NT+) were retrospectively collected from HIV positive individuals at four sites (one Southeastern, one Mid-Western States). The age ranged from 19-60 years old (median = 41 years). Sixteen (16) women and 71 men were included in this group (the age and gender of the other samples were not disclosed). The samples were collected between February 2012 and June 2015 and stored at -20°C until the time of testing.
These samples were tested on the GSD AIX1000 RPR Automated Test System and the comparator device. All samples were tested in-house by a single operator. The identity of the samples was masked and the samples from HIV positive individuals were randomized with samples collected from HIV negative individuals. Reactive and non-reactive controls were tested with the assay on each day of testing. No invalid results were obtained. The results are summarized below:
| HIV Positive | Comparator Device | |||
|---|---|---|---|---|
| Reactive | Non-reactive | Total | ||
| GSD AIX1000 RPR | ||||
| Test System | Reactive | 30 | 0 | 30 |
| Non-reactive | 0 | 250 | 250 | |
| Total | 30 | 250 | 280 |
The positive percent agreement and negative percent of the GSD AIX1000 RPR Automated Test System with the comparator (along with their 95% confidence intervals) are 100% (C.I. 90.5% - 100%) and 100% (C.I. 98.8% - 100%), respectively.
Apparently Healthy Individuals
To determine the percentage of RPR reactivity with the GSD AIX1000 RPR Automated Test System in a population of apparently healthy individuals, 100 serum samples prospectively collected from healthy individuals not at risk for syphilis and for whom a syphilis test had not been ordered (samples were submitted to the source laboratories for routine chemistry testing) were tested with the GSD AIX1000 RPR Automated Test System. All 100 samples were non-reactive with the GSD AIX1000 RPR Automated Test System.
The percentage of RPR reactivity with the GSD AIX1000 RPR Automated Test system in the 765 prospective serum samples collected from two geographically distinct regions of the United States from patients with a physician's order to perform syphilis testing, 2.9% (22/765) were reactive with the GSD AIX1000 RPR Automated Test System.
Correlation with Clinically Diagnosed Syphilis Sera - Various Stages
A sample panel of sera collected from patients clinically positive for syphilis at various stages of the disease were purchased. The sera consisted of treated samples at the primary, secondary, and latent stages of syphilis. The age, gender, and collection dates for the samples were
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not disclosed. The primary syphilis samples given were characterized by documented genital lesion with positive dark field microscopy (if performed) and with reactive treponemal test. The secondary syphilis samples were characterized by documented rash or mucous patches or condyloma lata with reactive treponemal test. And the latent syphilis samples were characterized by having reactive treponemal and non-treponemal test with a non-reactive non-treponemal test for more than a year or for an unknown duration of infection.
The sera were tested on both the GSD AIX1000 RPR Automated Test System and on the comparator device. The sample panel members were masked and the order of testing was randomized. There were no invalid results reported in any of the tests. The results are summarized below:
| | GSD AIX1000 RPR Test System and
Comparator Device Results | | | |
|---------------------|--------------------------------------------------------------|---------------------|-------------|--------------|
| Clinical Diagnosis | # Reactive* | # Non-
reactive* | % Agreement | 95% C.I. |
| Primary Treated | 13 | 0 | 100% | 79.4% - 100% |
| Primary Untreated | 12 | 0 | 100% | 77.9% - 100% |
| Secondary Treated | 25 | 0 | 100% | 88.7% - 100% |
| Secondary Untreated | 25 | 0 | 100% | 88.7% - 100% |
| Latent Treated | 25 | 0 | 100% | 88.7% - 100% |
| Latent Untreated | 25 | 0 | 100% | 88.7% - 100% |
Note: The results of the sample population tested may not be consisted with what has been reported in the literature. It is important to perform follow-up testing on patients suspected of having syphilis.
7 Conclusion:
From the data, we conclude that the Gold Standard Diagnostics AIX1000 Rapid Plasma Reagin (RPR) Automated Test System is substantially equivalent to the predicate device - the Arlington Scientific Inc. (ASI) RPR Card Test for syphilis on the ASiManager-AT Analyzer (K111356).