(90 days)
Not Found
No
The device description details a standard immunometric assay technique and the performance studies evaluate the device against a composite comparator algorithm using other FDA-cleared tests. There is no mention of AI or ML in the device description, intended use, or performance evaluation.
No
The device is for the qualitative determination of antibodies to aid in the diagnosis of syphilis infection, not for treatment.
Yes
The "Intended Use / Indications for Use" states that the device "may aid in the diagnosis of syphilis infection." This directly indicates its role in diagnosing a medical condition.
No
The device description clearly outlines a physical reagent pack and calibrator used with a specific hardware system (VITROS 5600 Integrated System) to perform an immunometric assay. This involves chemical reactions and light signal detection, indicating a hardware-dependent process, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states "For the qualitative determination of total (IgG and IgM) antibodies to Treponema pallidum (TP) specific antigens in human serum and plasma". This involves testing biological samples (serum and plasma) in vitro (outside the body) to obtain diagnostic information.
- Device Description: The description details a laboratory test using reagents and a system to analyze a sample. This is characteristic of an in vitro diagnostic device.
- Performance Studies: The document describes clinical performance studies using human samples to evaluate the device's accuracy in detecting syphilis antibodies. This is a requirement for IVD devices seeking regulatory clearance.
- Predicate Device(s): The mention of predicate devices (Elecsys Syphilis) which are also IVDs further supports that this device falls under the IVD category.
The device performs a test on a biological sample (serum and plasma) to aid in the diagnosis of a disease (syphilis), which is the core function of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
For the qualitative determination of total (IgG and IgM) antibodies to Treponema pallidum (TP) specific antigens in human serum and plasma using the VITROS 5600 Integrated System.
The presence of antibodies to Treponema pallidum (TP) specific antigens, in conjunction with non-treponemal laboratory tests and clinical findings may aid in the diagnosis of syphilis infection.
The VITROS Syphilis test is not intended for blood and tissue donor screening.
Product codes (comma separated list FDA assigned to the subject device)
LIP
Device Description
The VITROS Immunodiagnostic Products Syphilis test is performed using the VITROS Immunodiagnostic Products Syphilis Reagent Pack and VITROS Immunodiagnostic Products Syphilis Calibrator on the VITROS 5600 Integrated System.
An immunometric technique is used; this involves a two-stage reaction. In the first stage antibodies to Syphilis TP specific antigens present in the sample bind with biotinylated recombinant Syphilis TP antigens immobilized on streptavidin coated wells. Unbound sample is removed by washing. In the second stage conjugate reagent containing horseradish peroxidase (HRP)-labeled recombinant Syphilis TP antigens is added. The conjugate binds specifically to any antibody to Syphilis TP specific antigens captured on the well in the first stage. Unbound conjugate is removed by washing.
The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system.
VITROS Immunodiagnostic Products Syphilis Reagent Pack contains:
1 reagent pack containing:
- 100 coated wells; biotin-recombinant Syphilis TP antigens, 0.15 ug/mL.
- 13.1 mL assay reagent (buffer with bovine gamma globulin, bovine serum albumin and antimicrobial agent).
- 20.4 mL conjugate reagent (HRP-recombinant Syphilis TP antigens, 0.15 µg/mL) in buffer with bovine serum albumin and antimicrobial agent.
VITROS Syphilis Calibrator contains:
- 1 vial of VITROS Syphilis Calibrator (human anti-Syphilis TP antigen in anti-Syphilis TP antigen negative human plasma with antimicrobial agent, 2.2 mL).
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
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Indicated Patient Age Range
Not Found
Intended User / Care Setting
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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
A total of 924 prospective specimens from the intended use population collected from 6 sites in the United States were tested at 3 sites using the VITROS Syphilis test, including 615 subjects sent for routine syphilis testing, 47 pregnant women and 262 HIV positive subjects. In addition, all samples were tested according to a composite testing algorithm using FDA-cleared tests that included a treponemal electrochemiluminescence immunoassay (TP-ECLIA), a Rapid Plasma Reagin (RPR) non-treponemal assay and a Treponema pallidum Particle Agglutination (TP-PA) Treponema-specific assay.
A total of 547 retrospective purchased samples were tested at 3 sites using the VITROS Syphilis test, including 243 samples from pregnant women, 152 HIV positive samples and 152 pre-selected positive samples. In addition, all samples were tested according to a composite testing algorithm using FDA-cleared tests that included treponemal electrochemiluminescence immunoassay (TP-ECLIA), a Rapid Plasma Reagin (RPR) non-treponemal specific assay and a Treponema-pallidum Particle Agglutination (TP-PA) Treponema-specific assay.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Nonclinical Performance
Stability Studies: Long term stability and on-board storage performance was evaluated consistent with methods based on CLSI EP25-A. Long Term Stability supports a claim of 21 weeks stability currently. On-board Stability supports a claim of 12 weeks on-board stability.
Precision: The within-laboratory precision of the VITROS Syphilis test was evaluated with five serum pools (PP) following CLSI document EP05. 15 Two reagent lots and calibrator lots were included in the study. For each reagent lot, operators ran two replicates of each precision pool on two occasions per day for 20 non-consecutive days.
The within-laboratory coefficient of variation (CV) ranged from 12.0% to 18.8% for reactive and non-reactive samples respectively.
Reproducibility: A five-level reproducibility panel was tested with one lot of reagents at three sites, twice a day, with two unique operators a day, three replicates per run, for a total of five testing days. Reproducibility (total) CV ranged from 4.0% to 4.9% for reactive and non-reactive samples respectively.
Matrix Comparison: Serum and plasma (Heparin and EDTA) specimen matrices were determined to be equivalent.
Sample Stability: Samples evaluated at room temperature, refrigerated, and frozen conditions. Claimed storage conditions for specimens (Serum, Serum (SST), Serum (PST), Plasma (PST), Li-Heparin, K2 EDTA and K3EDTA) at 2 to 8°C for 7 days, Room temperature for 7 days, Frozen for 28 days. Samples may be frozen and thawed up to 5 times.
Carryover: A carryover study verified that the VITROS Syphilis test is not affected by sample carry over.
Detection of Syphilis IgG and IgM: A study confirmed the VITROS Immunodiagnostic Products Syphilis reagent pack is capable of specifically detecting syphilis IgG and IgM antibodies.
Analytical Specificity: Evaluated for potential interference consistent with CLSI documents EP07 and EP37. None of the tested common substances interfered with clinical interpretation at indicated concentrations in negative and weakly reactive samples.
Cross-Reactivity: Evaluated in anti-syphilis TP negative samples from medical conditions unrelated to syphilis infection. No cross-reactivity was observed with various conditions including ANA, Borrelia burgdorferi, CMV, EBV, Hepatitis A/B/C, HSV-1/2, RA/RF, Rubella, Hyperglobulinemia, SLE, Toxoplasmosis, VZV, E. coli, Leptospirosis, and VCA (EBV Viral Capsid Antigen). Two HIV samples and five VZV samples initially reactive were confirmed positive for anti-Treponema pallidum antibodies by another syphilis total antibody assay, indicating coinfection rather than cross-reactivity.
Clinical Studies
Clinical Performance in Prospectively Collected Specimens:
Sample size: 924 prospective specimens.
Positive Percent Agreement (PPA): 99.5% (218/219) (95% CI: 97.5 - 99.9).
Negative Percent Agreement (NPA): 97.6% (688/705) (95% CI: 96.2 - 98.5).
Breakdown by subgroup:
Routine Syphilis: PPA 98.8% (83/84), NPA 99.2% (527/531).
Pregnant Women: PPA 100.0% (1/1), NPA 97.8% (45/46).
HIV Positive: PPA 100.0% (134/134), NPA 90.6% (116/128).
Clinical Performance in Retrospective Specimens:
Sample size: 547 retrospective purchased samples.
PPA: 100.0% (213/213).
NPA: 98.8% (330/334).
Breakdown by subgroup:
Pregnant Women: PPA 100.0% (31/31), NPA 100.0% (212/212).
HIV Positive: PPA 100.0% (30/30), NPA 96.7% (118/122).
Pre-selected Positive: PPA 100.0% (152/152), NPA N/A.
Clinical Performance in Pregnant Women:
Total samples: 290 (47 prospective, 243 retrospective).
Prospectively Collected Specimens Overall: PPA 100.0% (1/1), NPA 97.8% (45/46).
Retrospective Specimens Overall: PPA 100.0% (31/31), NPA 100.0% (212/212).
Clinical Performance in HIV Positive Individuals:
Total samples: 414 (262 prospective, 152 retrospective).
Prospectively Collected Specimens: PPA 100.0% (134/134), NPA 90.6% (116/128).
Retrospective Specimens: PPA 100.0% (30/30), NPA 96.7% (118/122).
Clinical Performance in Medically Diagnosed Individuals:
Sample size: 151.
All 151 samples (primary, secondary, and latent syphilis, treated and untreated) were reactive with the VITROS Syphilis test.
Clinical Performance in Apparently Healthy Individuals:
Sample size: 201.
Reactive rate: 2.0% (4/201). Three of these were positive by the Final Comparator.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA).
For Prospectively Collected Specimens:
PPA: 99.5% (218/219) (95% CI: 97.5 - 99.9)
NPA: 97.6% (688/705) (95% CI: 96.2 - 98.5)
For Retrospective Specimens:
PPA: 100.0% (213/213)
NPA: 98.8% (330/334)
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.
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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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
August 28, 2024
Ortho Clinical Diagnostics Rebecca Lewis Senior Regulatory Affairs Associate Felindre Meadows Pencoed Bridgend, CF35 5PZ United Kingdom
Re: K241534
Trade/Device Name: VITROS Immunodiagnostic Products Syphilis Reagent Pack Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema Pallidum Treponemal Test Reagents Regulatory Class: Class II Product Code: LIP Dated: May 30, 2024 Received: May 30, 2024
Dear Rebecca Lewis:
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 (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.
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).
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 Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Enclosure
3
Indications for Use
510(k) Number (if known) K241534
Device Name
VITROS Immunodiagnostic Products Syphilis Reagent Pack (VITROS Syphilis test)
Indications for Use (Describe)
VITROS Immunodiagnostic Products Syphilis Reagent Pack (VITROS Syphilis test)
For the qualitative determination of total (IgG and IgM) antibodies to Treponema pallidum (TP) specific antigens in human serum and plasma using the VITROS 5600 Integrated System.
The presence of antibodies to Treponema pallidum (TP) specific antigens, in conjunction with non-treponemal laboratory tests and clinical findings may aid in the diagnosis of syphilis infection.
The VITROS Syphilis test is not intended for blood and tissue donor screening.
Type of Use (Select one or both, as applicable)X Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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4
510(k) Summary
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. The assigned 510(k) number is: K241534.
Submitter's Information
Ortho Clinical Diagnostics
Felindre Meadows,
Pencoed,
UK CF35 5PZ Phone: +44 (0) 7971 427649
Fax: 585-453-4110 Contact Person: Rebecca Lewis
Preparation Date
August 27, 2024
Device Proprietary Name(s)
VITROS Immunodiagnostic Products Syphilis Reagent Pack
Common Name(s) VITROS Syphilis test
Classification Names
| Product Code | Class | Regulation Section | Panel |
|---|---|---|---|
| LIP | II | 21 CFR 866.3830 | |
| Division of Microbiology Devices (DMD) | Microbiology |
Predicate Device(s)
| Predicate Device | FDA 510(k) Number |
|---|---|
| Elecsys Syphilis | K160910 & K211302 |
Device Description
The VITROS Immunodiagnostic Products Syphilis test is performed using the VITROS Immunodiagnostic Products Syphilis Reagent Pack and VITROS Immunodiagnostic Products Syphilis Calibrator on the VITROS 5600 Integrated System.
An immunometric technique is used; this involves a two-stage reaction. In the first stage antibodies to Syphilis TP specific antigens present in the sample bind with biotinylated recombinant Syphilis TP antigens immobilized on streptavidin coated wells. Unbound sample is removed by washing. In the second stage conjugate reagent containing horseradish peroxidase (HRP)-labeled recombinant Syphilis TP antigens is added. The conjugate binds specifically to any antibody to Syphilis TP specific antigens captured on the well in the first stage. Unbound conjugate is removed by washing.
5
The bound HRP conjugate is measured by a luminescent reaction. A reagent containing luminogenic substrates (a luminol derivative and a peracid salt) and an electron transfer agent is added to the wells. The HRP in the bound conjugate catalyzes the oxidation of the luminol derivative, producing light. The electron transfer agent (a substituted acetanilide) increases the level of light produced and prolongs its emission. The light signals are read by the system.
VITROS Immunodiagnostic Products Syphilis Reagent Pack contains:
1 reagent pack containing:
- 100 coated wells; biotin-recombinant Syphilis TP antigens, 0.15 ug/mL. ●
- 13.1 mL assay reagent (buffer with bovine gamma globulin, bovine serum albumin and antimicrobial agent).
- 20.4 mL conjugate reagent (HRP-recombinant Syphilis TP antigens, 0.15 µg/mL) in buffer with bovine serum albumin and antimicrobial agent.
VITROS Syphilis Calibrator contains:
- 1 vial of VITROS Syphilis Calibrator (human anti-Syphilis TP antigen in anti-Syphilis ● TP antigen negative human plasma with antimicrobial agent, 2.2 mL).
Intended Use Statement(s):
VITROS Immunodiagnostic Products Syphilis Reagent Pack (VITROS Syphilis test) For the qualitative determination of total (IgG and IgM) antibodies to Treponema pallidum (TP) specific antigens in human serum and plasma using the VITROS 5600 Integrated System.
The presence of antibodies to Treponema pallidum (TP) specific antigens, in conjunction with non-treponemal laboratory tests and clinical findings may aid in the diagnosis of syphilis infection.
The VITROS Syphilis test is not intended for blood and tissue donor screening.
Comparison to Predicate Devices
The following table provides a summary of the key features of the new device assessed against the predicate.
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| Device Characteristic | Predicate Device | New Device |
|---|---|---|
| Roche Elecsys Syphilis assay, | ||
| K160910 and K211302, cleared 28 | ||
| July 2016 and 20 July 2021 | VITROS Immunodiagnostic Products | |
| Syphilis Reagent Pack | ||
| Intended Use | For the in vitro qualitative detection of total | |
| antibodies (IgGand IgM) to Treponema pallidum in human serum and plasma. |
The test is intended as an aid in the diagnosis
of syphilis infection in conjunction with
clinical signs and symptoms.
The Elecsys Syphilis immunoassay is not
intended for use in screening blood or tissue
donors. The effectiveness of this assay in
testing blood or tissue donors has not been
established.
The electrochemiluminescence immunoassay
"ECLIA" is intended for use
on cobas e immunoassay analyzers. | VITROS Immunodiagnostic Products Syphilis
Reagent Pack (VITROS Syphilis test)
For the qualitative determination of total (IgG
and IgM) antibodies to Treponema pallidum
(TP) specific antigens in human serum and
plasma using the VITROS 5600 Integrated
System.
The presence of antibodies to Treponema
pallidum (TP) specific antigens, in conjunction
with non-treponemal laboratory tests and clinical
findings may aid in the diagnosis of syphilis
infection.
The VITROS Syphilis test is not intended for
blood and tissue donor screening. |
| Basic Principle | Sandwich immunoassay. | Same. |
| Analyte | Anti-Syphilis TPA. | Same. |
| Sample Type | Serum and Plasma. | Same. |
| Automated | Automated assay. | Same. |
| Measurement | Qualitative. | Same. |
| Interpretation of
results | Samples with a cutoff index anti-Treponema pallidum
antibodies.
Samples with a cutoff index ≥ 1.00 are
considered reactive. | Same. |
General Device Characteristic Differences:
| Traceability | N/A. | Traceable to an in-house reference calibrator
which has been value assigned to optimize
clinical sensitivity and specificity. |
|-------------------|-------|-------------------------------------------------------------------------------------------------------------------------------------|
| Sample Volume | 6 µL. | 25 µL. |
| Calibrator Levels | 2. | 1. |
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VITROS Immunodiagnostic Products Syphilis Reagent Pack Traditional 510(k)
Nonclinical Performance
Several nonclinical tests were performed.
Stability Studies
Long term stability and on-board storage performance was evaluated consistent with methods based on CLSI EP25-A.
Long Term Stability: Four runs have been performed on each of 3 Lots at each time-point, monthly intervals, will support a 52 week shelf-life. All results were acceptable and support a claim of 21 weeks stability currently.
On-board Stability: Three Lots of the VITROS Immunodiagnostic Products Syphilis reagent pack were stored opened refrigerated for up to 13 weeks. Four runs were performed on each Lot at each time-point for fresh and open, all results were acceptable and support a claim of 12 weeks on-board stability.
Result Calculation
Result = Signal for test sample Signal at Cutoff (Cutoff value)
Interpretation of results
Samples with results less than 1.00 will be flagged as "Non-reactive" and samples with results greater than or equal to 1.00 will be flagged as "Reactive".
| VITROS Syphilis Test
| Result (S/C) | Status | Interpretation |
|---|---|---|