(109 days)
Abbott ARCHITECT™ Syphilis TP, 8D06
Not Found
No
The device description details a standard immunoassay process based on chemical reactions and light measurement, with no mention of AI or ML algorithms for data analysis or interpretation. The performance studies describe traditional statistical analysis of assay results.
No
The device is an in vitro diagnostic (IVD) assay intended for the qualitative detection of antibodies to Treponema pallidum as an aid in the diagnosis of syphilis. It does not provide any therapeutic function; rather, it aids in the diagnosis.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended to be used as an aid in the diagnosis of syphilis."
No
The device description clearly outlines a physical immunoassay kit with reagents, paramagnetic particles, and a process involving incubation, washing, and measurement using a luminometer. This indicates a hardware-based diagnostic test, not a software-only device.
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 assay is for the qualitative detection of total antibodies to Treponema pallidum in human serum and plasma. This is a test performed in vitro (outside the body) on biological samples to provide information for diagnosis.
- Device Description: The description details a laboratory-based immunoassay process involving reagents, samples, and an instrument to measure light production, which is a characteristic of in vitro testing.
- Clinical Performance Studies: The document describes clinical studies where patient specimens were tested in a laboratory setting using the device and compared to other laboratory tests. This is typical for the evaluation of an IVD.
- Intended User / Care Setting: The intended users are clinical laboratory technicians, and the samples are requested by healthcare providers, indicating a laboratory testing environment.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K153730) and name (Abbott ARCHITECT™ Syphilis TP) is a strong indicator that this device is being submitted for regulatory review as an IVD, as predicate devices are used for comparison in the regulatory process for IVDs.
N/A
Intended Use / Indications for Use
The Access Syphilis assay is a paramagnetic particle, chemiluminescent immunoassay for the qualitative detection of total antibodies to Treponema pallidum in human serum and plasma using the Access Immunoassay Systems. It is intended to be used as an aid in the diagnosis of syphilis or in conjunction with a nontreponemal laboratory test and clinical findings to aid in the diagnosis of syphilis infection. The Access Syphilis assay is not intended for blood and tissue donor screening.
Product codes (comma separated list FDA assigned to the subject device)
LIP
Device Description
The Access Syphilis assay is a two-step enzyme immunoassay. A sample is added to a reaction vessel with buffer, paramagnetic particles coated with recombinant Treponema pallidum antigens Tp17 and Tp47, and Tp47, and biotinylated Treponema Tp17 & Tp47 antigens. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Alkaline phosphatase conjugates are added, and the conjugates bind to the immunoglobulin captured on the particles. A chemilyminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is proportional to the amount of Treponema pallidum antibodies in the sample. The light quantity measured for a sample allows a determination of the presence of the analyte by comparison with a cut-off value defined during the assay calibration on the instrument.
The Access Syphilis reagents are provided in liquid ready-to-use format designed for optimal performance on the Beckman Coulter Access Immunoassay Systems. Each reagent kit contains two reagent packs.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
12 to > 89 years
Intended User / Care Setting
Health Care Providers requesting samples to be tested by clinical laboratory technicians
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Summary of Studies - Access 2 Immunoassay System
Imprecision
The imprecision of the Access Syphilis assay on the Access 2 Immunoassay Systems was evaluated in a study based on CLSI EP05-A3 guidance. The within-laboratory intermediate precision study included two test runs per day over 20 test days. A four-member panel of serum (S1-S4) samples and the Access Syphilis QC were assayed in each run (in duplicate). Three lots of Access Syphilis reagent and calibrator were tested on an Access 2 Immunoassay Analyzer for the study.
Between-Lot Precision
A six-member panel, including serum samples (S1-S4) and two assay controls, were assayed at three clinical sites, using three lots of Access Syphilis reagent to obtain between-lot precision. Each panel member was assayed in replicates of four, twice a day over 5 days.
Reproducibility
A 5-day between lab reproducibility study was performed on the Access 2 Immunoassay Systems based on CLSI EP05- A3 quidance. A six-member panel, including serum samples (S1-S4) and two assay controls, were assayed at three clinical sites, using three lots of Access Syphilis reagent on three instruments. Each panel member was assayed in replicates of four at two separate times per day.
Interfering Substances
The Access Syphilis assay was evaluated for interference consistent with CLSI document EP07 3rd Edition. Testing was performed using two nonreactive (one low negative and one high negative) and two reactive (one low positive and one positive) samples.
Cross Reactivity
Cross-reactivity was evaluated by testing samples for potentially cross-reacting conditions. 337 samples across various categories were tested.
Clinical Performance Evaluation - Access 2 Immunoassay System
A total of 1,104 prospectively collected specimens from the intended use population were tested using the Access Syphilis assay. 704 (63.8%) were female and 400 (36.2%) were male, with an age range of 12 to > 89 years. The Access Syphilis assay was reactive in 214 (19.4%) of specimens collected from the intended use population.
Clinical Performance
A multicenter study was conducted to evaluate the clinical performance of the Access Syphilis assay. A total of 1,910 specimens were included in this study with 1,104 prospectively collected specimens from the intended use population, 402 retrospective specimens from patients, 204 prospectively collected specimens from apparently healthy individuals, 150 retrospecimens from patients with medically diagnosed syphilis, and 50 retrospective specimens from individuals at high-risk of sexually transmitted disease. The specimens were tested at three sites in a randomized and blinded fashion (all cohorts), using the Access Syphilis assay, and a final comparator result was obtained using a composite testing algorithm consisting of the following FDA-approved assays: the predicate treponemal immunoassay, a nontreponemal assay (RPR - Rapid Plasma Reagin), and a second treponemal assay (TPPA -Treponema Pallidum Particle Agglutination).
Clinical Performance in Intended Use Population
A total of 1,104 specimens from the intended use population were prospectively collected and tested with Access Syphilis and the composite testing algorithm. The study included specimens from 399 patients sent for syphilis testing, 405 pregnant women and 300 HIV positive patients. The overall positive percent agreement was 100% (184/184) with a 95% confidence interval of 98.0 to 100% and the overall negative percent agreement was 96.7% (890/920) with a 95% confidence interval of 95.4 to 97.7%.
Clinical Performance in Retrospective Specimens
A cohort of 402 retrospective specimens were included in the study, of which 22 were from pregnant females. The positive percent agreement was 100% (398/398) with a 95% confidence interval of 99.0 to 100% and the negative percent agreement was 25.0% (1/4) with a 95% confidence interval of 4.6 to 69.9%.
Clinical Performance in Apparently Healthy Individuals
Of the total 1,910 specimens in the study, 204 were prospectively collected from apparently healthy individuals.
Clinical Performance in Medically Diagnosed Patients
A total of 150 retrospective specimens from patients with medically diagnosed syphilis (primary, secondary, and latent stages) were included in the study.
Clinical Performance in Pregnant Females
A total of 427 pregnant female specimens were included in the study, with 405 prospectively collected and 22 retrospectively collected specimens.
Clinical Performance in High-Risk Individuals
Of the total 1,910 specimens in the study, 50 retrospective specimens were from individuals at high-risk of sexually transmitted disease. The positive percent agreement was 100% (20/20) with a 95% confidence interval of 83.9 to 100% and the negative percent agreement was 80.0% (24/30) with a 95% confidence interval of 62.7 to 90.5%.
Summary of Studies – Dxl 9000 Immunoassay Analyzer
Imprecision
The imprecision of the Access Syphilis assay on the Dxl 9000 Access Immunoassay Analyzer was evaluated in a study based on CLSI EP05-A3 guidance. The within-laboratory intermediate precision study included two test runs per day over 20 test days. A four-member panel of serum (S1-S4) samples and the Access Syphilis QC were assayed in each run (in duplicate). Three lots of Access Syphilis reagent and calibrator were tested on two Dxl 9000 Access Immunoassay Analyzers for the study, with each lot tested on one instrument.
Between-Lot Precision
A six-member panel, including serum samples (S1-S4) and two assay controls, were assayed at three clinical sites, using three lots of Access Syphilis reagent to obtain between-lot precision. Each panel member was assayed in replicates of four, twice a day over 5 days.
Reproducibility
A 5-day between lab reproducibility study was performed on the Dxl 9000 Access Immunoassay analyzer based on CLSI EP05-A3 guidance14. A six-member panel, including serum samples (S1-S4) and two assay controls, were assayed at three clinical sites, using three lots of Access Syphilis reagent on three instruments. Each panel member was assayed in replicates of four at two separate times per day.
Interfering Substances
The Access Syphilis assay was evaluated for interference consistent with CLSI document EP07 3rd Edition. Testing was performed using two nonreactive (one low negative and one high negative) and two reactive (one low positive) samples.
Cross Reactivity
Cross-reactivity was evaluated by testing samples for potentially cross-reacting conditions. 337 samples across various categories were tested.
Clinical Performance Evaluation - Dxl 9000 Immunoassay Analyzer
A total of 1,104 prospectively collected specimens from the intended use population were tested using the Access Syphilis assay. 704 (63.8%) were female and 400 (36.2%) were male, with an age range of 12 to > 89 years. The Access Syphilis assay was reactive in 214 (19.4%) of specimens collected from the intended use population.
Clinical Performance
A multicenter study was conducted to evaluate the clinical performance of the Access Syphilis assay. A total of 1,910 specimens were included in this study with 1,104 prospectively collected specimens from the intended use population, 402 retrospective specimens , 204 prospectively collected specimens from apparently healthy individuals, 150 retrospective specimens with medically diagnosed syphilis, and 50 retrospective specimens from individuals at high-risk of sexually transmitted disease. The specimens were tested at three sites in a randomized and blinded fashion (all cohorts), using the Access Syphilis assay, and a final comparator result was obtained using a composite testing algorithm consisting of the following FDA-approved assays: the predicate treponemal immunoassay, a nontreponemal assay (RPR - Rapid Plasma Reagin), and a second treponemal assay (TPPA -Treponema Pallidum Particle Agglutination).
Clinical Performance in Intended Use Population
A total of 1,104 specimens from the intended use population were prospectively collected with Access Syphilis and the composite testing algorithm. The study included specimens from 399 patients sent for syphilis testing, 405 pregnant women and 300 HIV positive patients. The overall positive percent agreement was 100% (184/184) with a 95% confidence interval of 98.0 to 100% and the overall negative percent agreement was 96.7% (890/920) with a 95% confidence interval of 95.4 to 97.7%.
Clinical Performance in Retrospective Specimens
A cohort of 402 retrospective specimens from patients were included in the study, of which 22 were from pregnant females. The positive percent agreement was 100% (398/398) with a 95% confidence interval of 99.0 to 100% and the negative percent agreement was 25.0% (1/4) with a 95% confidence interval of 4.6 to 69.9%.
Clinical Performance in Apparently Healthy Individuals
Of the total 1,910 specimens in the study, 204 were prospectively collected from apparently healthy individuals.
Clinical Performance in Medically Diagnosed Patients
A total of 150 retrospective specimens from patients with medically diagnosed syphilis (primary, secondary, and latent stages) were included in the study.
Clinical Performance in Pregnant Females
A total of 427 pregnant female specimens were included in the study, with 405 prospectively collected and 22 retrospective specimens.
Clinical Performance in High-Risk Individuals
Of the total 1,910 specimens in the study, 50 retrospective specimens were from individuals at high-risk of sexually transmitted disease. The positive percent agreement was 100% (20/20) with a 95% confidence interval of 83.9 to 100% and the negative percent agreement was 80.0% (24/30) with a 95% confidence interval of 62.7 to 90.5%.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Access 2 Immunoassay System
Clinical Performance in Intended Use Population
The overall positive percent agreement was 100% (184/184) with a 95% confidence interval of 98.0 to 100% and the overall negative percent agreement was 96.7% (890/920) with a 95% confidence interval of 95.4 to 97.7%.
Routine Syphilis Testing: Positive Percent Agreement: 100% (60/60) (95% CI: 94.0 - 100); Negative Percent Agreement: 99.7% (338/339) (95% CI: 98.4 - 100).
Pregnant Women: Positive Percent Agreement: 100% (6/6) (95% CI: 61.0 - 100); Negative Percent Agreement: 99.8% (398/399) (95% CI: 98.6 - 100).
HIV Positive Patients: Positive Percent Agreement: 100% (118/118) (95% CI: 96.9 - 100); Negative Percent Agreement: 84.6% (154/182) (95% CI: 78.7 - 89.1).
Clinical Performance in Retrospective Specimens
The positive percent agreement was 100% (398/398) with a 95% confidence interval of 99.0 to 100% and the negative percent agreement was 25.0% (1/4) with a 95% confidence interval of 4.6 to 69.9%.
Clinical Performance in Pregnant Females (Total)
Positive Percent Agreement: 100% (6/6) (95% CI: 61.0 - 100); Negative Percent Agreement: 99.8% (398/399) (95% CI: 98.6 - 100) for prospectively collected specimens.
Positive Percent Agreement: 100% (20/20) (95% CI: 83.9 - 100); Negative Percent Agreement: 50.0% (1/2) (95% CI: 9.5 - 90.6) for retrospective specimens.
Clinical Performance in High-Risk Individuals
Positive Percent Agreement: 100% (20/20) with a 95% confidence interval of 83.9 to 100% and the negative percent agreement was 80.0% (24/30) with a 95% confidence interval of 62.7 to 90.5%.
Dxl 9000 Immunoassay Analyzer
Clinical Performance in Intended Use Population
The overall positive percent agreement was 100% (184/184) with a 95% confidence interval of 98.0 to 100% and the overall negative percent agreement was 96.7% (890/920) with a 95% confidence interval of 95.4 to 97.7%.
Routine Syphilis Testing: Positive Percent Agreement: 100% (60/60) (95% CI: 94.0 - 100); Negative Percent Agreement: 99.7% (338/339) (95% CI: 98.4 - 100).
Pregnant Women: Positive Percent Agreement: 100% (6/6) (95% CI: 61.0 - 100); Negative Percent Agreement: 99.8% (398/399) (95% CI: 98.6 - 100).
HIV Positive Patients: Positive Percent Agreement: 100% (118/118) (95% CI: 96.9 - 100); Negative Percent Agreement: 84.6% (154/182) (95% CI: 78.7 - 89.1).
Clinical Performance in Retrospective Specimens
The positive percent agreement was 100% (398/398) with a 95% confidence interval of 99.0 to 100% and the negative percent agreement was 25.0% (1/4) with a 95% confidence interval of 4.6 to 69.9%.
Clinical Performance in Pregnant Females (Total)
Prospectively Collected: Positive Percent Agreement: Total 100% (6/6) (95% CI: 61.0 - 100); Negative Percent Agreement: Total 99.8% (398/399) (95% CI: 98.6 - 100).
Retrospective Specimens: Positive Percent Agreement: Total 100% (20/20) (95% CI: 83.9 - 100); Negative Percent Agreement: Total 50.0% (1/2) (95% CI: 9.5 - 90.6).
Clinical Performance in High-Risk Individuals
The positive percent agreement was 100% (20/20) with a 95% confidence interval of 83.9 to 100% and the negative percent agreement was 80.0% (24/30) with a 95% confidence interval of 62.7 to 90.5%.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Abbott ARCHITECT™ Syphilis TP, 8D06
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3830
Treponema pallidum treponemal test reagents.(a)
Identification. Treponema pallidum treponemal test reagents are devices that consist of the antigens, antisera and all control reagents (standardized reagents with which test results are compared) which are derived from treponemal sources and that are used in the fluorescent treponemal antibody absorption test (FTA-ABS), theTreponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies toTreponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genusTreponema and provides epidemiological information on syphilis.(b)
Classification. Class II (performance standards).
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Beckman Coulter, Inc Brenda Eifert Staff Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318
Re: K241427
Trade/Device Name: Access Syphilis Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema Pallidum Treponemal Test Reagents Regulatory Class: Class II Product Code: LIP Dated: May 17, 2024 Received: May 20, 2024
Dear Brenda Eifert:
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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"
1
(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
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Sincerely, Himani Bisht -S
Himani Bisht, Ph.D. Assistant Director Viral Respiratory and HPV Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
Submission Number (if known)
K241427 Device Name
Access Syphilis
Indications for Use (Describe)
The Access Syphilis assay is a paramagnetic particle, chemiluminescent immunoassay for the qualitative detection of total antibodies to Treponema pallidum in human serum and plasma using the Access lmmunoassay Systems. It is intended to be used as an aid in the diagnosis of syphilis or in conjunction with a nontreponemal laboratory test and clinical findings to aid in the diagnosis of syphilis infection. The Access Syphilis assay is not intended for blood and tissue donor screening.
Type of Use (Select one or both, as applicable)
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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510(k) Summarv
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
510(k) Number: K241427
Date Prepared: September 6, 2024
Submitter Name and Address:
Beckman Coulter, Inc 1000 Lake Hazeltine Drive Chaska. MN 55318
Primary Contact:
Brenda Eifert Staff Requlatory Affairs Email: beifert@beckman.com Phone: (800) 854-3633
Alternate Contact: Loretta Lydon O'Toole
Staff Requlatory Affairs Email: lotoole@beckman.com Phone: (800) 854-3633
Trade Name: Access Syphilis Common Name: Treponema pallidum treponemal test reagents Classification Requlation: 21 CFR 866.3830 Classification Product Code: LIP
Predicate Device: Abbott ARCHITECT™ Syphilis TP. 8D06
Device Description
The Access Syphilis assay is a two-step enzyme immunoassay. A sample is added to a reaction vessel with buffer, paramagnetic particles coated with recombinant Treponema pallidum antigens Tp17 and Tp47, and Tp47, and biotinylated Treponema Tp17 & Tp47 antigens. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Alkaline phosphatase conjugates are added, and the conjugates bind to the immunoglobulin captured on the particles. A chemilyminescent substrate is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is proportional to the amount of Treponema pallidum antibodies in the sample. The light quantity measured for a sample allows a determination of the presence of the analyte by comparison with a cut-off value defined during the assay calibration on the instrument.
The Access Syphilis reagents are provided in liquid ready-to-use format designed for optimal performance on the Beckman Coulter Access Immunoassay Systems. Each reagent kit contains two reagent packs.
Intended Use
The Access Syphilis assay is a paramagnetic particle, chemiluminescent immunoassay for the qualitative detection of total antibodies to Treponema pallidum in human serum and plasma using the Access Immunoassay Systems. It is intended to be used as an aid in the diagnosis of syphilis or in conjunction with a non-treponemal laboratory test and clinical findings to aid in the diagnosis of syphilis infection. The Access Syphilis assay is not intended for blood and tissue donor screening.
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| Features /
Characteristics | Candidate Device
Access Syphilis | Predicate Device (K153730)
ARCHITECT Syphilis |
|-----------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Reagent Intended Use
and Clinical
Indications | Access Immunoassay Systems IFU:
The Access Syphilis assay is a
paramagnetic particle,
chemiluminescent immunoassay for the
qualitative detection of total antibodies
to Treponema pallidum in human serum
and plasma using the Access
Immunoassay Systems. It is intended
to be used as an aid in the diagnosis
of syphilis or in conjunction with a
nontreponemal laboratory test and
clinical findings to aid in the
diagnosis of syphilis infection. The
Access Syphilis assay is not intended
for blood and tissue donor screening. | The ARCHITECT Syphilis TP assay is
a chemiluminescent microparticle
immunoassay (CMIA) for the
qualitative detection of antibodies (IgG
and IgM) directed against Treponema
pallidum (TP) in human serum and
plasma. The ARCHITECT Syphilis
TP assay is intended to be used as
an initial diagnostic test or in
conjunction with a nontreponemal
laboratory test and clinical findings
to aid in the diagnosis of syphilis
infection.
Warning: The ARCHITECT Syphilis
TP assay is not intended for use in
screening blood, plasma, or tissue
donors. The effectiveness of the
ARCHITECT Syphilis TP assay for
use in screening blood, plasma, or
tissue donors has not been
established. |
| Environment of Use | Health Care Providers requesting
samples to be tested by clinical
laboratory technicians | Same |
| Operating Principle | Chemiluminescent microparticle
immunoassay (CMIA) | Same |
| Antigen sources | Recombinant Treponema pallidum
antigens Tp17 and Tp47, and
biotinylated Treponema Tp17 & Tp47
antigens | Recombinant TP antigens: TpN15,
TpN17 and TpN47 (obtained in E.coli ) |
| Assay Type | Two-step sandwich enzyme
immunoassay | Same |
| Detection Method | Automated, Chemiluminescence | Same |
| Reagent format | Liquid, ready to use | Same |
| Sample Type | Serum and Plasma | Same |
| Features /
Characteristics | Candidate Device
Access Syphilis | Predicate Device (K153730)
ARCHITECT Syphilis |
| Compatible
Anticoagulants | Human Serum:
Serum and serum separator tube
Human Plasma:
Lithium Heparin
Lithium Heparin separator tube
Dipotassium (K₂) EDTA
Tripotassium (K₃) EDTA
Sodium Citrate
Acid Citrate Dextrose (ACD)
Citrate Phosphate Dextrose (CPD)
Citrate Phosphate Dextrose with
Adenine (CPDA) | Human Serum:
Serum and serum separator tube
Human Plasma:
Dipotassium EDTA
Tripotassium EDTA
Lithium heparin plasma separator
Lithium heparin
Sodium heparin |
| Sample Volume | ~45 µL | 30 µL |
| Instrumentation | Access Immunoassay Systems:
Access 2 Immunoassay System Dxl 9000 Access Immunoassay Analyzer | ARCHITECT iSystem |
| Test Result Reporting | Reactive, Non-reactive and S/CO | Reactive, Non-reactive and S/CO |
| Time to Result | Access 2 Immunoassay System ~30 minutes Dxl 9000 Access Immunoassay Analyzer ~22 minutes | ~ 29 minutes |
| Reagent Storage and
Stability | Unopened at 2 to 10°C up to stated
expiration date | Unopened at 2 to 8°C up to stated
expiration date |
| Reagent On-board
Stability | 56 Days | 30 days |
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Summary of Studies - Access 2 Immunoassay System
Imprecision
The assay was designed to have within-laboratory imprecision as listed below:
- ·
- · ≤ 10.0% CV at concentrations ≥ 1.00 S/CO
The imprecision of the Access Syphilis assay on the Access 2 Immunoassay Systems was evaluated in a study based on CLSI EP05-A3 guidance.
The within-laboratory intermediate precision study included two test runs per day over 20 test days. A four-member panel of serum (S1-S4) samples and the Access Syphilis QC were assayed in each run (in duplicate). Three lots of Access Syphilis reagent and calibrator were tested on an Access 2 Immunoassay Analyzer for the study. The results are presented below:
| Between Lot | Between Day | Between Run | Within Run | Overall | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean | ||||||||||
| (S/CO) | SD | |||||||||||
| (S/CO) | %CV | SD | ||||||||||
| (S/CO) | %CV | SD | ||||||||||
| (S/CO) | %CV | SD | ||||||||||
| (S/CO) | %CV | SD | ||||||||||
| (S/CO) | %CV | |||||||||||
| QC1 | 240 | 0.107 | 0.029 | N/A | 0.009 | N/A | 0.007 | N/A | 0.007 | N/A | 0.032 | N/A |
| QC2 | 240 | 1.704 | 0.083 | 4.9% | 0.057 | 3.4% | 0.074 | 4.3% | 0.048 | 2.8% | 0.134 | 7.9% |
| S1 (Low Negative) | 240 | 0.064 | 0.004 | N/A | 0.003 | N/A | 0.004 | N/A | 0.003 | N/A | 0.007 | N/A |
| S2 (High Negative) | 240 | 0.708 | 0.018 | 2.6% | 0.023 | 3.2% | 0.022 | 3.2% | 0.017 | 2.5% | 0.041 | 5.8% |
| S3 (Low Positive) | 240 | 1.819 | 0.116 | 6.4% | 0.061 | 3.4% | 0.051 | 2.8% | 0.039 | 2.2% | 0.146 | 8.0% |
| S4 (Positive) | 240 | 6.721 | 0.491 | 7.3% | 0.216 | 3.2% | 0.203 | 3.0% | 0.179 | 2.7% | 0.601 | 8.9% |
Note: %CV are not meaningful when dose approaches zero. Results are noted as N/A.
Between-Lot Precision
A six-member panel, including serum samples (S1-S4) and two assay controls, were assayed at three clinical sites, using three lots of Access Syphilis reagent to obtain between-lot precision. Each panel member was assayed in replicates of four, twice a day over 5 days. The results are summarized in the following table.
| | | | Within Reagent
Pack Lot | | | Between Reagent
Pack Lot | | Total | |
|--------------------|-----|----------------|----------------------------|-----|--------------|-----------------------------|--------------|-------|--|
| Sample | N | Mean
(S/CO) | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV | |
| QC1 | 360 | 0.10 | 0.01 | N/A | 0.02 | N/A | 0.03 | N/A | |
| QC2 | 360 | 1.56 | 0.09 | 5.5 | 0.01 | 0.9 | 0.09 | 5.5 | |
| S1 (Low Negative) | 360 | 0.06 | 0.01 | N/A | 0.00 | N/A | 0.01 | N/A | |
| S2 (High Negative) | 360 | 0.75 | 0.03 | 4.3 | 0.01 | 1.9 | 0.03 | 4.7 | |
| S3 (Low Positive) | 360 | 1.89 | 0.09 | 4.5 | 0.06 | 3.1 | 0.10 | 5.5 | |
| S4 (Positive) | 360 | 7.19 | 0.30 | 4.2 | 0.25 | 3.5 | 0.39 | 5.4 | |
Note: %CV are not meaningful when dose approaches zero. Results are noted as N/A.
8
Reproducibility
A 5-day between lab reproducibility study was performed on the Access 2 Immunoassay Systems based on CLSI EP05- A3 quidance. A six-member panel, including serum samples (S1-S4) and two assay controls, were assayed at three clinical sites, using three lots of Access Syphilis reagent on three instruments. Each panel member was assayed in replicates of four at two separate times per day. The results are summarized in the following table.
| | | | Repeatability
(Within Run) | | | Between Run | | Between Day | | Between Lot | | Between Site | | Reproducibility | |
|-----------------------|-----|----------------|-------------------------------|-----|--|--------------|-----|--------------|-----|--------------|-----|--------------|------|-----------------|-----|
| Sample | N | Mean
(S/CO) | SD
(S/CO) | %CV | | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV |
| QC1 | 360 | 0.10 | 0.004 | N/A | | 0.005 | N/A | 0.006 | N/A | 0.025 | N/A | 0.005 | N/A | 0.027 | N/A |
| QC2 | 360 | 1.56 | 0.043 | 2.8 | | 0.058 | 3.7 | 0.016 | 1.0 | 0.010 | 0.6 | 0.054 | 3.4% | 0.092 | 5.9 |
| S1 (Low
Negative) | 360 | 0.06 | 0.003 | N/A | | 0.003 | N/A | 0.003 | N/A | 0.005 | N/A | 0.005 | N/A | 0.009 | N/A |
| S2 (High
Negative) | 360 | 0.75 | 0.019 | 2.6 | | 0.018 | 2.4 | 0.018 | 2.5 | 0.013 | 1.8 | 0.005 | 0.6% | 0.035 | 4.7 |
| S3 (Low
Positive) | 360 | 1.89 | 0.042 | 2.2 | | 0.065 | 3.5 | 0.037 | 2.0 | 0.058 | 3.1 | 0.000 | N/A | 0.104 | 5.5 |
| S4
(Positive) | 360 | 7.19 | 0.223 | 3.1 | | 0.197 | 2.7 | 0.000 | N/A | 0.247 | 3.4 | 0.068 | 0.9% | 0.393 | 5.5 |
Note: %CV are not meaningful when dose approaches zero. Results are noted as N/A.
INTERFERING SUBSTANCES
The Access Syphilis assay was evaluated for interference consistent with CLSI document EP07 3rd Edition. Testing was performed using two nonreactive (one low negative and one high negative) and two reactive (one low positive and one positive) samples. Of the endogenous compounds tested, none were found to cause interference at the highest test concentrations indicated in the following table.
| Potential Interferent | Highest Concentration |
|---|---|
| Hemoglobin | 1,000 mg/dL |
| Total Protein | 15 g/dL |
| Bilirubin - conjugated | 40 mg/dL |
| Bilirubin - unconjugated | 40 mg/dL |
| Triolein | 36 g/L |
| Biotin | 0.351 mg/dL |
| Gamma globulin | 47.5 g/L* |
*Interference was noted at a concentration of 60 g/L. A dose effect study was conducted, with no interference observed ≤47.5 g(L.
The following pharmaceutical substances were also evaluated and no interference with the assay was observed: acetylsalicylic acid (aspirin), acetaminophen (paracetamol), ibuprofen, azithromycin, ceftriaxone sodium, doxycycline hyclate.
9
Cross Reactivity
Cross-reactivity was evaluated by testing samples for potentially cross-reacting conditions. No crossreactivity was observed. The results are summarized in the following table.
| Category | Number of Samples
Tested | Number of
Reactive Samples | Number of
Nonreactive
Samples |
|----------------------------------------------------------------------------------|-----------------------------|-------------------------------|-------------------------------------|
| Pregnant multipara | 14 | 0 | 14 |
| Hemodialysis patients | 10 | 0 | 10 |
| Transplant patients | 10 | 0 | 10 |
| Rheumatoid Factor (RF) | 10 | 0 | 10 |
| Human Anti-mouse Antibody (HAMA) | 10 | 0 | 10 |
| Anti-Nuclear Antibody (ANA) | 10 | 0 | 10 |
| Lyme Disease (Borrelia garinii, Borrelia afzelii
& Borrelia burgdorferi s.s.) | 10 | 0 | 10 |
| Toxoplasma gondii IgG | 5 | 0 | 5 |
| Toxoplasma gondii IgM | 5 | 0 | 5 |
| Epstein Barr Virus (EBV) IgG | 10 | 0 | 10 |
| Epstein Barr Virus (EBV) IgM | 10 | 0 | 10 |
| Leptospirosis | 10 | 0 | 10 |
| Systemic Lupus Erythemateous (SLE) | 10 | 0 | 10 |
| Hepatitis A Virus (HAV) Total Ab | 5 | 0 | 5 |
| Hepatitis A Virus (HAV) IgM | 5 | 0 | 5 |
| Hepatitis B Virus (HBV) - HBs Ag positive | 10 | 0 | 10 |
| Hepatitis B Virus (HBV) -anti-HBs positive | 22 | 0 | 22 |
| Hepatitis B Virus (HBV) - HBc IgM positive | 9 | 0 | 9 |
| Hepatitis B Virus (HBV) - Anti HBc total positive | 20 | 0 | 20 |
| Hepatitis C Virus (HCV) | 10 | 0 | 10 |
| HTLV-1 | 10 | 0 | 10 |
| HTLV-2 | 13 | 0 | 13 |
| Human Immunodeficiency Virus (HIV)-1 | 8 | 0 | 8 |
| Human Immunodeficiency Virus (HIV)-2 | 9 | 0 | 9 |
| Herpes Simplex Virus (HSV) 1& 2 IgM | 15 | 0 | 15 |
| Herpes Simplex Virus (HSV) 1 IgG | 10 | 0 | 10 |
| Herpes Simplex Virus (HSV) 2 IgG | 2 | 0 | 2 |
| Cytomegalovirus (CMV) IgG | 5 | 0 | 5 |
| Cytomegalovirus (CMV) IgM | 5 | 0 | 5 |
| Rubella IgG | 5 | 0 | 5 |
| Rubella IgM | 10 | 0 | 10 |
| Anti-Escherichia coli (E.coli) | 10 | 0 | 10 |
| Multiple myeloma | 10 | 0 | 10 |
| Flu vaccinated patients | 10 | 0 | 10 |
| Anti-Phospholipid | 10 | 0 | 10 |
| TOTAL | 337 | 0 | 337 |
10
Clinical Performance Evaluation - Access 2 Immunoassay System
A total of 1,104 prospectively collected specimens from the intended use population were tested using the Access Syphilis assay. 704 (63.8%) were female and 400 (36.2%) were male, with an age range of 12 to > 89 years. The Access Syphilis assay was reactive in 214 (19.4%) of specimens collected from the intended use population.
| Age Range
| (Years) | Gender | Total | Access Syphilis Assay | |
|---|---|---|---|---|
| Reactive N | ||||
| (%) | Nonreactive N | |||
| (%) | ||||
| 12-20 | Male | 7 | 0 (0.0) | 7 (100.0) |
| 12-20 | Female | 48 | 2 (4.2) | 46 (95.8) |
| 21-30 | Male | 44 | 9 (20.4) | 35 (79.6) |
| 21-30 | Female | 256 | 8 (3.1) | 248 (96.9) |
| 31-40 | Male | 72 | 36 (50.0) | 36 (50.0) |
| 31-40 | Female | 211 | 12 (5.7) | 199 (94.3) |
| 41-50 | Male | 87 | 38 (43.7) | 49 (56.3) |
| 41-50 | Female | 68 | 9 (13.2) | 59 (86.8) |
| 51-60 | Male | 123 | 54 (43.9) | 69 (56.1) |
| 51-60 | Female | 68 | 17 (25.0) | 51 (75.0) |
| 61-70 | Male | 54 | 16 (29.6) | 38 (70.4) |
| 61-70 | Female | 38 | 10 (26.3) | 28 (73.7) |
| 71-89* | Male | 13 | 2 (15.4) | 11 (84.6) |
| 71-89* | Female | 15 | 1 (6.7) | 14 (93.3) |
| Total | 1,104 | 214 (19.4) | 890 (80.6) |
Distribution of the Access Syphilis Reactive results in the intended use population by age and gender
- NOTE: One (1) subject was > 89 years
Clinical Performance
A multicenter study was conducted to evaluate the clinical performance of the Access Syphilis assay. A total of 1,910 specimens were included in this study with 1,104 prospectively collected specimens from the intended use population, 402 retrospective specimens from patients, 204 prospectively collected specimens from apparently healthy individuals, 150 retrospecimens from patients with medically diagnosed syphilis, and 50 retrospective specimens from individuals at high-risk of sexually transmitted disease.
The specimens were tested at three sites in a randomized and blinded fashion (all cohorts), using the Access Syphilis assay, and a final comparator result was obtained using a composite testing algorithm consisting of the following FDA-approved assays: the predicate treponemal immunoassay, a nontreponemal assay (RPR - Rapid Plasma Reagin), and a second treponemal assay (TPPA -Treponema Pallidum Particle Agglutination).
11
Clinical Performance in Intended Use Population
A total of 1,104 specimens from the intended use population were prospectively collected and tested with Access Syphilis and the composite testing algorithm described above. The study included specimens from 399 patients sent for syphilis testing, 405 pregnant women and 300 HIV positive patients.
| Predicate
Treponemal
Immunoassay | RPR | TPPA | Final
Comparator
Result | Access Syphilis
Result | N |
|----------------------------------------|-----|------|-------------------------------|---------------------------|-------|
| - | - | NA | - | - | 878 |
| - | + | - | - | - | 5 |
| - | + | + | + | - | 0 |
| + | - | - | - | - | 7 |
| + | - | + | + | - | 0 |
| + | + | NA | + | - | 0 |
| - | + | INC | - | - | 0 |
| + | + | NA | + | + | 79 |
| + | - | + | + | + | 104 |
| + | - | - | - | + | 12 |
| - | + | + | + | + | 0 |
| - | + | - | - | + | 0 |
| - | - | - | - | + | 13 |
| - | - | + | - | + | 5 |
| + | - | INC | + | + | 1 |
| | | | | Total | 1,104 |
Summary of the Serological Profile for all Prospectively Collected Specimens from the Intended Use Population
- = Reactive; - = Nonreactive; NA = not performed; INC = Inconclusive
The overall positive percent agreement was 100% (184/184) with a 95% confidence interval of 98.0 to 100% and the overall negative percent agreement was 96.7% (890/920) with a 95% confidence interval of 95.4 to 97.7%
Percent Agreement for Intended Use Subpopulations
| Positive Percent Agreement | Negative Percent Agreement | |||
|---|---|---|---|---|
| Subpopulation | n/N | % | ||
| (95% CI) | n/N | % | ||
| (95% CI) | ||||
| Routine Syphilis Testing | 60/60 | 100 | ||
| (94.0 - 100) | 338/3391 | 99.7 | ||
| (98.4 - 100) | ||||
| Pregnant Women | 6/6 | 100 | ||
| (61.0 - 100) | 398/399 | 99.8 | ||
| (98.6 - 100) | ||||
| HIV Positive Patients | 118/118 | 100 | ||
| (96.9 - 100) | 154/1822 | 84.6 | ||
| (78.7 - 89.1) | ||||
| Total | 184/184 | 100 | ||
| (98.0 - 100) | 890/920 | 96.7 | ||
| (95.4 - 97.7) |
^ One (1) specimen from the routine syphilis testine by an FDA-cleared treponemal immunoassay and nonreactive by RPR and TPPA.
²Twenty-five (25) out of twenty-eight (28) discordants were found to be reactive using an additional FDA-cleared electrochemiluminescent immunoassay. Eleven (11) of these were also reactive by the predicate treponemal immunoassay.
12
Clinical Performance in Retrospective Specimens
A cohort of 402 retrospective specimens were included in the study, of which 22 were from pregnant females.
| Predicate
Treponemal
Immunoassay | RPR | TPPA | Final
Comparator
Result | Access Syphilis
Result | N |
|----------------------------------------|-----|------|-------------------------------|---------------------------|-----|
| - | - | NA | - | - | 1 |
| - | + | - | - | - | 0 |
| - | + | + | + | - | 0 |
| + | - | - | - | - | 0 |
| + | - | + | + | - | 0 |
| + | + | NA | + | - | 0 |
| - | + | INC | - | - | 0 |
| + | + | NA | + | + | 324 |
| + | - | + | + | + | 74 |
| + | - | - | - | + | 3 |
| - | + | + | + | + | 0 |
| - | + | - | - | + | 0 |
| - | - | - | - | + | 0 |
| - | - | + | - | + | 0 |
| + | - | INC | + | + | 0 |
| Total | | | | | 402 |
Summary of the Serological Profile for Retrospective Specimens
- = Reactive; - = Nonreactive; NA = not performed; INC = Inconclusive
Comparison between the Access Syphilis Results and the Final Comparator Results in Retrospective Specimens
| Retrospective Specimens | Final Comparator Result | |||
|---|---|---|---|---|
| Reactive | Nonreactive | Total | ||
| Access Syphilis | ||||
| Result | Reactive | 398 | 31 | 401 |
| Nonreactive | 0 | 1 | 1 | |
| Total | 398 | 4 | 402 |
1Three (3) specimens were reactive by treponemal immunoassay and nonreactive by RPR and TPPA
The positive percent agreement was 100% (398/398) with a 95% confidence interval of 99.0 to 100% and the negative percent agreement was 25.0% (1/4) with a 95% confidence interval of 4.6 to 69.9%.
13
Clinical Performance in Apparently Healthy Individuals
Of the total 1,910 specimens in the study, 204 were prospectively collected from apparently healthy individuals. Results of the Access Syphilis assay are shown below:
| Access Syphilis Result | ||
|---|---|---|
| Apparently Healthy Individuals | Reactive (%) | Nonreactive (%) |
| 18 (8.8) | 186 (91.2) |
Clinical Performance in Medically Diagnosed Patients
A total of 150 retrospective specimens from patients with medically diagnosed syphilis (primary, secondary, and latent stages) were included in the study. Results of the Access Syphilis assay are shown in the following table:
| Syphilis Stage | Treatment Status | N | Access Syphilis | |
|---|---|---|---|---|
| Reactive | Nonreactive | |||
| Primary | Untreated | 49 | 49 | 0 |
| Primary | Treated | 27 | 26 | 11 |
| Secondary | Untreated | 13 | 13 | 0 |
| Secondary | Treated | 23 | 23 | 0 |
| Latent | Untreated | 13 | 7 | 61 |
| Latent | Treated | 25 | 25 | 0 |
1 These seven (7) specimens also tested nonreactive with an FDA-cleared treponemal immunoassay.
Clinical Performance in Pregnant Females
A total of 427 pregnant female specimens were included in the study, with 405 prospectively collected and 22 retrospectively collected specimens. Percent Agreement Between Access Syphilis and the Final Comparator Result by Trimester
| Trimester | N | Positive Percent
Agreement
% (x/n) | 95%
Confidence
Interval (%) | Negative Percent
Agreement
% (x/n) | 95%
Confidence
Interval (%) |
|-------------------------|-----|------------------------------------------|-----------------------------------|------------------------------------------|-----------------------------------|
| Prospectively Collected | | | | | |
| First Trimester | 60 | 100 (1/1) | 20.7 - 100 | 100 (59/59) | 93.9 - 100 |
| Second Trimester | 38 | 100 (1/1) | 20.7 - 100 | 100 (37/37) | 90.6 - 100 |
| Third Trimester | 307 | 100 (4/4) | 51.0 - 100 | 99.7 (302/303) | 98.2 - 99.9 |
| Unknown Trimester | 0 | NA | NA | NA | NA |
| Total | 405 | 100 (6/6) | 61.0 - 100 | 99.8 (398/399) | 98.6 - 100 |
| Retrospective Specimens | | | | | |
| First Trimester | 6 | 100 (6/6) | 61.0 - 100 | NA (0/0) | NA |
| Second Trimester | 9 | 100 (9/9) | 70.1 - 100 | NA (0/0) | NA |
| Third Trimester | 6 | 100 (5/5) | 56.6 - 100 | 100 (1/1) | 20.7 - 100 |
| Unknown Trimester | 1 | NA (0/0) | 20.7 - 100 | 0 (0/1) | 0 - 79.4 |
| Total | 22 | 100 (20/20) | 83.9 - 100 | 50.0 (1/2) | 9.5 - 90.6 |
NA - Not applicable
14
Clinical Performance in High-Risk Individuals
Of the total 1,910 specimens in the study, 50 retrospective specimens were from individuals at highrisk of sexually transmitted disease.
Comparison Between the Access Syphilis Results and the Final Comparator Results in High-Risk Individuals
| High-Risk Individuals | Final Comparator Result | |||
|---|---|---|---|---|
| Reactive | Nonreactive | Total | ||
| Access Syphilis | ||||
| Result | Reactive | 20 | 61 | 26 |
| Nonreactive | 0 | 24 | 24 | |
| Total | 20 | 30 | 50 |
1 One (1) specimen was reactive by treponemal immunoassay and nonreactive by RPR and TPPA
The percent agreement was 100% (20/20) with a 95% confidence interval of 83.9 to 100% and the negative percent agreement was 80.0% (24/30) with a 95% confidence interval of 62.7 to 90.5%.
15
Summary of Studies – Dxl 9000 Immunoassay Analyzer
Imprecision
The assay was designed to have within-laboratory imprecision as listed below:
- ·
- · ≤ 10.0% CV at concentrations ≥ 1.00 S/CO
The imprecision of the Access Syphilis assay on the Dxl 9000 Access Immunoassay Analyzer was evaluated in a study based on CLSI EP05-A3 guidance.
The within-laboratory intermediate precision study included two test runs per day over 20 test days. A four-member panel of serum (S1-S4) samples and the Access Syphilis QC were assayed in each run (in duplicate). Three lots of Access Syphilis reagent and calibrator were tested on two Dxl 9000 Access Immunoassay Analyzers for the study, with each lot tested on one instrument. The results are presented below:
| | | | Between Lot &
Instrument | | Between Day | | Between Run | | Within Run | | Overall | |
|-----------------------|-----|----------------|-----------------------------|------|--------------|------|--------------|------|--------------|------|--------------|------|
| Sample | N | Mean
(S/CO) | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV |
| QC1 | 238 | 0.166 | 0.064 | N/A | 0.007 | N/A | 0.007 | N/A | 0.008 | N/A | 0.065 | N/A |
| QC2 | 238 | 1.786 | 0.082 | 4.6% | 0.059 | 3.3% | 0.088 | 4.9% | 0.041 | 2.3% | 0.140 | 7.8% |
| S1 (Low
Negative) | 240 | 0.078 | 0.018 | N/A | 0.003 | N/A | 0.003 | N/A | 0.005 | N/A | 0.019 | N/A |
| S2 (High
Negative) | 239 | 0.779 | 0.065 | 8.4% | 0.021 | 2.8% | 0.023 | 3.0% | 0.019 | 2.4% | 0.075 | 9.6% |
| S3 (Low
Positive) | 240 | 1.994 | 0.078 | 3.9% | 0.048 | 2.4% | 0.072 | 3.6% | 0.046 | 2.3% | 0.125 | 6.3% |
| S4 (Positive) | 240 | 7.598 | 0.294 | 3.9% | 0.241 | 3.2% | 0.240 | 3.2% | 0.163 | 2.1% | 0.478 | 6.3% |
Note: %CV are not meaningful when dose approaches zero. Results are noted as N/A.
16
Between-Lot Precision
A six-member panel, including serum samples (S1-S4) and two assay controls, were assayed at three clinical sites, using three lots of Access Syphilis reagent to obtain between-lot precision. Each panel member was assayed in replicates of four, twice a day over 5 days. The results are summarized in the following table.
| | | | Within Reagent
Pack Lot | | Between Reagent
Pack Lot | | Total | |
|--------------------|-----|----------------|----------------------------|-----|-----------------------------|-----|--------------|-----|
| Sample | N | Mean
(S/CO) | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV |
| QC1 | 360 | 0.10 | 0.013 | N/A | 0.033 | N/A | 0.035 | N/A |
| QC2 | 360 | 1.59 | 0.087 | 5.5 | 0.005 | 0.3 | 0.087 | 5.5 |
| S1 (Low Negative) | 360 | 0.05 | 0.007 | N/A | 0.007 | N/A | 0.010 | N/A |
| S2 (High Negative) | 360 | 0.75 | 0.045 | 6.0 | 0.019 | 2.6 | 0.048 | 6.5 |
| S3 (Low Positive) | 360 | 1.94 | 0.109 | 5.6 | 0.056 | 2.9 | 0.122 | 6.3 |
| S4 (Positive) | 360 | 7.48 | 0.537 | 7.2 | 0.303 | 4.0 | 0.616 | 8.2 |
Note: %CV are not meaningful when dose approaches zero. Results are noted as N/A.
Reproducibility
A 5-day between lab reproducibility study was performed on the Dxl 9000 Access Immunoassay analyzer based on CLSI EP05-A3 guidance14. A six-member panel, including serum samples (S1-S4) and two assay controls, were assayed at three clinical sites, using three lots of Access Syphilis reagent on three instruments. Each panel member was assayed in replicates of four at two separate times per day. The results are summarized in the following table.
| | | Repeatability
(Within Run) | Between Run | | Between Day | | Between Lot | | Between Site | | Reproducibility | | | |
|-----------------------|-----|-------------------------------|--------------|-----|--------------|-----|--------------|-----|--------------|-----|-----------------|-----|--------------|-----|
| Sample | N | Mean
(S/CO) | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV | SD
(S/CO) | %CV |
| QC1 | 360 | 0.10 | 0.005 | N/A | 0.003 | N/A | 0.009 | N/A | 0.033 | N/A | 0.010 | N/A | 0.036 | N/A |
| QC2 | 360 | 1.59 | 0.037 | 2.3 | 0.050 | 3.2 | 0.059 | 3.7 | 0.000 | N/A | 0.019 | 1.2 | 0.088 | 5.5 |
| S1 (Low
Negative) | 360 | 0.05 | 0.003 | N/A | 0.001 | N/A | 0.004 | N/A | 0.007 | N/A | 0.005 | N/A | 0.010 | N/A |
| S2 (High
Negative) | 360 | 0.75 | 0.017 | 2.3 | 0.018 | 2.4 | 0.029 | 3.8 | 0.018 | 2.4 | 0.030 | 4.0 | 0.052 | 6.9 |
| S3 (Low
Positive) | 360 | 1.94 | 0.044 | 2.3 | 0.060 | 3.1 | 0.070 | 3.6 | 0.053 | 2.7 | 0.052 | 2.7 | 0.126 | 6.5 |
| S4
(Positive) | 360 | 7.48 | 0.271 | 3.6 | 0.271 | 3.6 | 0.213 | 2.8 | 0.297 | 4.0 | 0.387 | 5.2 | 0.655 | 8.8 |
Note: %CV are not meaningful when dose approaches zero. Results are noted as N/A.
17
Interfering Substances
The Access Syphilis assay was evaluated for interference consistent with CLSI document EP07 3rd Edition. Testing was performed using two nonreactive (one low negative and one high negative) and two reactive (one low positive) samples. Of the endogenous compounds tested, none were found to cause interference at the highest test concentrations indicated in the following table.
| Potential Interferent | Highest Concentration |
|---|---|
| Hemoglobin | 1,000 mg/dL |
| Total Protein | 15 g/dL |
| Bilirubin - conjugated | 40 mg/dL |
| Bilirubin - unconjugated | 40 mg/dL |
| Triolein | 36 g/L |
| Biotin | 0.351 mg/dL |
| Gamma globulin | 47.5 g/L* |
*Interference was noted at a concentration of 60 g/L. A dose effect study was conducted, with no interference observed s47.5 g(L.
The following pharmaceutical substances were also evaluated and no interference with the assay was observed: acetylsalicylic acid (aspirin), acetaminophen (paracetamol), ibuprofen, azithromycin, ceftriaxone sodium, doxycycline hyclate.
18
Cross Reactivity
Cross-reactivity was evaluated by testing samples for potentially cross-reacting conditions. No cross-reactivity was observed. The results are summarized in the following table.
| Category | Number of Samples
Tested | Number of
Reactive Samples | Number of
Nonreactive Samples |
|----------------------------------------------------------------------------------|-----------------------------|-------------------------------|----------------------------------|
| Pregnant multipara | 14 | 0 | 14 |
| Hemodialysis patients | 10 | 0 | 10 |
| Transplant patients | 10 | 0 | 10 |
| Rheumatoid Factor (RF) | 10 | 0 | 10 |
| Human Anti-mouse Antibody (HAMA) | 10 | 0 | 10 |
| Anti-Nuclear Antibody (ANA) | 10 | 0 | 10 |
| Lyme Disease (Borrelia garinii, Borrelia
afzelii & Borrelia burgdorferi s.s.) | 10 | 0 | 10 |
| Toxoplasma gondii IgG | 5 | 0 | 5 |
| Toxoplasma gondii IgM | 5 | 0 | 5 |
| Epstein Barr Virus (EBV) IgG | 10 | 0 | 10 |
| Epstein Barr Virus (EBV) IgM | 10 | 0 | 10 |
| Leptospirosis | 10 | 0 | 10 |
| Systemic Lupus Erythematous (SLE) | 10 | 0 | 10 |
| Hepatitis A Virus (HAV) Total Ab | 5 | 0 | 5 |
| Hepatitis A Virus (HAV) IgM | 5 | 0 | 5 |
| Hepatitis B Virus (HBV) - HBs Ag positive | 10 | 0 | 10 |
| Hepatitis B Virus (HBV) -anti-HBs positive | 22 | 0 | 22 |
| Hepatitis B Virus (HBV) - HBc IgM positive | 9 | 0 | 9 |
| Hepatitis B Virus (HBV) - Anti HBc total
positive | 20 | 0 | 20 |
| Hepatitis C Virus (HCV) | 10 | 0 | 10 |
| HTLV-1 | 10 | 0 | 10 |
| HTLV-2 | 13 | 0 | 13 |
| Human Immunodeficiency Virus (HIV)-1 | 8 | 0 | 8 |
| Human Immunodeficiency Virus (HIV)-2 | 9 | 0 | 9 |
| Herpes Simplex Virus (HSV) 1& 2 IgM | 15 | 0 | 15 |
| Herpes Simplex Virus (HSV) 1 IgG | 10 | 0 | 10 |
| Herpes Simplex Virus (HSV) 2 IgG | 2 | 0 | 2 |
| Cytomegalovirus (CMV) IgG | 5 | 0 | 5 |
| Cytomegalovirus (CMV) IgM | 5 | 0 | 5 |
| Rubella IgG | 5 | 0 | 5 |
| Rubella IgM | 10 | 0 | 10 |
| Anti-Escherichia coli (E.coli) | 10 | 0 | 10 |
| Multiple myeloma | 10 | 0 | 10 |
| Flu vaccinated patients | 10 | 0 | 10 |
| Anti-Phospholipid | 10 | 0 | 10 |
| TOTAL | 337 | 0 | 337 |
19
Clinical Performance Evaluation - Dxl 9000 Immunoassay Analyzer
A total of 1,104 prospectively collected specimens from the intended use population were tested using the Access Syphilis assay. 704 (63.8%) were female and 400 (36.2%) were male, with an age range of 12 to > 89 years. The Access Syphilis assay was reactive in 214 (19.4%) of specimens collected from the intended use population.
| Age Range
| (Years) | Gender | Total | Access Syphilis Assay | |
|---|---|---|---|---|
| Reactive | ||||
| N (%) | Nonreactive | |||
| N (%) | ||||
| 12-20 | Male | 7 | 0 (0.0) | 7 (100.0) |
| Female | 48 | 2 (4.2) | 46 (95.8) | |
| 21-30 | Male | 44 | 9 (20.4) | 35 (79.6) |
| Female | 256 | 8 (3.1) | 248 (96.9) | |
| 31-40 | Male | 72 | 36 (50.0) | 36 (50.0) |
| Female | 211 | 12 (5.7) | 199 (94.3) | |
| 41-50 | Male | 87 | 38 (43.7) | 49 (56.3) |
| Female | 68 | 9 (13.2) | 59 (86.8) | |
| 51-60 | Male | 123 | 54 (43.9) | 69 (56.1) |
| Female | 68 | 17 (25.0) | 51 (75.0) | |
| 61-70 | Male | 54 | 16 (29.6) | 38 (70.4) |
| Female | 38 | 10 (26.3) | 28 (73.7) | |
| 71-89* | Male | 13 | 2 (15.4) | 11 (84.6) |
| Female | 15 | 1 (6.7) | 14 (93.3) | |
| Total | 1,104 | 214 (19.4) | 890 (80.6) |
Distribution of the Access Syphilis Reactive and Nonreactive Results in the Intended Use Population by Age and Gender
- NOTE: One (1) subject was > 89 years
Clinical Performance
A multicenter study was conducted to evaluate the clinical performance of the Access Syphilis assay. A total of 1,910 specimens were included in this study with 1,104 prospectively collected specimens from the intended use population, 402 retrospective specimens , 204 prospectively collected specimens from apparently healthy individuals, 150 retrospective specimens with medically diagnosed syphilis, and 50 retrospective specimens from individuals at high-risk of sexually transmitted disease.
The specimens were tested at three sites in a randomized and blinded fashion (all cohorts), using the Access Syphilis assay, and a final comparator result was obtained using a composite testing algorithm consisting of the following FDA-approved assays: the predicate treponemal immunoassay, a nontreponemal assay (RPR - Rapid Plasma Reagin), and a second treponemal assay (TPPA -Treponema Pallidum Particle Agglutination).
Clinical Performance in Intended Use Population
A total of 1,104 specimens from the intended use population were prospectively collected with Access Syphilis and the composite testing algorithm described above. The study included specimens from 399 patients sent for syphilis testing, 405 pregnant women and 300 HIV positive patients.
20
| Predicate
Treponemal
Immunoassay | RPR | TPPA | Final
Comparator
Result | Access Syphilis
Result | N |
|----------------------------------------|-----|------|-------------------------------|---------------------------|-------|
| - | - | NA | - | - | 878 |
| - | + | - | - | - | 5 |
| - | + | + | + | - | 0 |
| + | - | - | - | - | 7 |
| + | - | + | + | - | 0 |
| + | + | NA | + | - | 0 |
| - | + | INC | - | - | 0 |
| + | + | NA | + | + | 79 |
| + | - | + | + | + | 104 |
| + | - | - | - | + | 12 |
| - | + | + | + | + | 0 |
| - | + | - | - | + | 0 |
| - | - | - | - | + | 13 |
| - | - | + | - | + | 5 |
| + | - | INC | + | + | 1 |
| | | | | Total | 1,104 |
Summary of the Serological Profile for all Prospectively Collected Specimens from the Intended Use Population
- = Reactive; - = Nonreactive; NA = not performed; INC = Inconclusive
The overall positive percent agreement was 100% (184/184) with a 95% confidence interval of 98.0 to 100% and the overall negative percent agreement was 96.7% (890/920) with a 95% confidence interval of 95.4 to 97.7%.
Percent Agreement for Intended Use Subpopulations
| Subpopulation | Positive Percent Agreement | Negative Percent Agreement | ||
|---|---|---|---|---|
| n/N | % | |||
| (95% CI) | n/N | % | ||
| (95% CI) | ||||
| Routine Syphilis Testing | 60/60 | 100 | ||
| (94.0 - 100) | 338/3391 | 99.7 | ||
| (98.4 - 100) | ||||
| Pregnant Women | 6/6 | 100 | ||
| (61.0 - 100) | 398/399 | 99.8 | ||
| (98.6 - 100) | ||||
| HIV Positive Patients | 118/118 | 100 | ||
| (96.9 - 100) | 154/1822 | 84.6 | ||
| (78.7 - 89.1) | ||||
| Total | 184/184 | 100 | ||
| (98.0 - 100) | 890/920 | 96.7 | ||
| (95.4 - 97.7) |
1 One (1) specimen from the routine syphilis testing cohort was reactive by an FDA-cleared treponemal immunoassay and nonreactive by RPR and TPPA
²Twenty-five (25) out of twenty-eight (28) discordants were found to be reactive using an additional FDA-cleared electrochemiluminescent immunoassay. Eleven (11) of these were also reactive by the predicate treponemal immunoassay.
Clinical Performance in Retrospective Specimens
A cohort of 402 retrospective specimens from patients were included in the study, of which 22 were from pregnant females.
21
| Predicate
Treponemal
Immunoassay | RPR | TPPA | Final
Comparator
Result | Access Syphilis
Result | N |
|----------------------------------------|-----|------|-------------------------------|---------------------------|-----|
| - | - | NA | - | - | 1 |
| - | + | - | - | - | 0 |
| - | + | + | + | - | 0 |
| + | - | - | - | - | 0 |
| + | - | + | + | - | 0 |
| + | + | NA | + | - | 0 |
| - | + | INC | - | - | 0 |
| + | + | NA | + | + | 324 |
| + | - | + | + | + | 74 |
| + | - | - | - | + | 3 |
| - | + | + | + | + | 0 |
| - | + | - | - | + | 0 |
| - | - | - | - | + | 0 |
| - | - | + | - | + | 0 |
| + | - | INC | + | + | 0 |
| | | | | Total I | 402 |
Summary of the Serological Profile for Retrospective Specimens
- = Reactive; - = Nonreactive; NA = not performed; INC = Inconclusive
Comparison Between the Access Syphilis Results and the Final Comparator Results in Retrospective Specimens
| Retrospective Specimens | Final Comparator Result | |||
|---|---|---|---|---|
| Reactive | Nonreactive | Total | ||
| Access Syphilis | ||||
| Result | Reactive | 398 | 3 1 | 401 |
| Nonreactive | 0 | 1 | 1 | |
| Total | 398 | 4 | 402 |
1Three (3) specimens were reactive by treponemal immunoassay and nonreactive by RPR and TPPA
The positive percent agreement was 100% (398/398) with a 95% confidence interval of 99.0 to 100% and the negative percent agreement was 25.0% (1/4) with a 95% confidence interval of 4.6 to 69.9%.
Clinical Performance in Apparently Healthy Individuals
Of the total 1,910 specimens in the study, 204 were prospectively collected from apparently healthy individuals. Results of the Access Syphilis assay are shown below:
| Access Syphilis Result | ||
|---|---|---|
| Apparently Healthy Individuals | Reactive (%) | Nonreactive (%) |
| 18 (8.8) | 186 (91.2) |
22
Clinical Performance in Medically Diagnosed Patients
A total of 150 retrospective specimens from patients with medically diagnosed syphilis (primary, secondary, and latent stages) were included in the study. Results of the Access Syphilis assay are shown in the following table:
| Syphilis Stage | Treatment Status | N | Access Syphilis | |
|---|---|---|---|---|
| Reactive | Nonreactive | |||
| Primary | Untreated | 49 | 49 | 0 |
| Primary | Treated | 27 | 26 | 11 |
| Secondary | Untreated | 13 | 13 | 0 |
| Secondary | Treated | 23 | 23 | 0 |
| Latent | Untreated | 13 | 7 | 61 |
| Latent | Treated | 25 | 25 | 0 |
1 These seven (7) specimens also tested nonreactive with an FDA-cleared treponemal immunoassay.
Clinical Performance in Pregnant Females
A total of 427 pregnant female specimens were included in the study, with 405 prospectively collected and 22 retrospective specimens.
Percent Agreement Between Access Syphilis and the Final Comparator Result by Trimester
| Trimester | N | Positive Percent
Agreement
% (x/n) | 95%
Confidenc
e Interval
(%) | Negative Percent
Agreement
% (x/n) | 95%
Confidence
Interval (%) | |
|-------------------------|-----|------------------------------------------|---------------------------------------|------------------------------------------|-----------------------------------|--|
| | | Prospectively Collected | | | | |
| First Trimester | 60 | 100 (1/1) | 20.7 - 100 | 100 (59/59) | 93.9 - 100 | |
| Second Trimester | 38 | 100 (1/1) | 20.7 - 100 | 100 (37/37) | 90.6 - 100 | |
| Third Trimester | 307 | 100 (4/4) | 51.0 - 100 | 99.7 (302/303) | 98.2 - 99.9 | |
| Unknown Trimester | 0 | NA | NA | NA | NA | |
| Total | 405 | 100 (6/6) | 61.0 - 100 | 99.8 (398/399) | 98.6 - 100 | |
| Retrospective Specimens | | | | | | |
| First Trimester | 6 | 100 (6/6) | 61.0 - 100 | NA (0/0) | NA | |
| Second Trimester | 9 | 100 (9/9) | 70.1 - 100 | NA (0/0) | NA | |
| Third Trimester | 6 | 100 (5/5) | 56.6 - 100 | 100 (1/1) | 20.7 - 100 | |
| Unknown Trimester | 1 | NA (0/0) | 20.7 - 100 | 0 (0/1) | 0 - 79.4 | |
| Total | 22 | 100 (20/20) | 83.9 - 100 | 50.0 (1/2) | 9.5 - 90.6 | |
NA - Not applicable
23
Clinical Performance in High-Risk Individuals
Of the total 1,910 specimens in the study, 50 retrospective specimens were from individuals at high-risk of sexually transmitted disease.
Comparison Between the Access Syphilis Results and the Final Comparator Results in High-Risk Individuals
| Final Comparator Result | ||||
|---|---|---|---|---|
| High-Risk Individuals | Reactive | Nonreactive | Total | |
| Reactive | 20 | 61 | 26 | |
| Access Syphilis Result | Nonreactive | 0 | 24 | 24 |
| Total | 20 | 30 | 50 |
1 One (1) specimen was reactive by treponemal immunoassay and nonreactive by RPR and TPPA
The positive percent agreement was 100% (20/20) with a 95% confidence interval of 83.9 to 100% and the negative percent agreement was 80.0% (24/30) with a 95% confidence interval of 62.7 to 90.5%.
24
Substantial Equivalence Comparison Conclusion
Beckman Coulter's Access Syphilis is substantially equivalent to the ARCHITECT Syphilis TP Reagent as demonstrated through the information and data provided in this submission. The performance and clinical testing presented in this submission provides evidence that the device is safe and effective for its intended use.