Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description details a standard immunoassay technology and does not mention any AI or ML components. The results are determined based on a direct relationship between light units and antibody levels, compared to established calibrators, which is a traditional method.

Therapeutic

No
The device is described as an "in-vitro diagnostic immunoassay for the qualitative determination of antibodies to Treponema pallidum," which is used for diagnosis, not for treatment.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "an in-vitro diagnostic immunoassay... as an aid in the diagnosis of syphilis." This directly indicates its function as a diagnostic tool.

SaMD (Software as a Medical Device)

No

The device is an in-vitro diagnostic immunoassay kit containing physical reagents, calibrators, and a master curve card, which are hardware components. It is used with the ADVIA Centaur® and ADVIA Centaur® XP systems, which are also hardware.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "The ADVIA Centaur Syphilis (SYPH) assay is an in-vitro diagnostic immunoassay for the qualitative determination of antibodies to Treponema pallidum in human serum or plasma... as an aid in the diagnosis of syphilis."

This statement clearly identifies the device as an in-vitro diagnostic product.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The ADVIA Centaur Syphilis (SYPH) assay is an in-vitro diagnostic immunoassay for the qualitative determination of antibodies to Treponema pallidum in human serum or plasma (EDTA. lithium or sodium heparinized, citrate) using the ADVIA Centaur® and ADVIA Centaur® XP systems as an aid in the diagnosis of syphilis. The ADVIA Centaur Syphilis assay is not intended for blood and tissue donor screening.

ADVIA® Centaur Syphilis Quality Control Materials are for in-vitro diagnostics use to monitor the performance of the Syphilis assay on the ADVIA Centaur® systems. The performance of the SYPH quality control material has not been established with any other Syphilis assay.

Product codes (comma separated list FDA assigned to the subject device)

LIP

Device Description

The ADVIA Centaur syphilis assay is a fully automated, antigen sandwich assay, using direct chemiluminometric technology. The ancillary pack reagent containing acridinium-ester-labeled T. pallidum recombinant antigens is added to the sample. These T. pallidum antigens complex with the antibodies in the sample. The solid phase containing biotinylated T. pallidum recombinant antigens preformed to streptavidin-coated magnetic latex particles, is then added to the sample. These particles capture the T. pallidum antigen-antibody complexes. Antibody-antigen complexes will form if Syphilis antibodies are present in the sample. A direct relationship exists between the level of antibodies to T. pallidum present in the patient sample and the amount of relative light units (RLUs) detected by the system. A result of reactive, nonreactive, or equivocal is determined according to the Index Value established with the calibrators.

The Syphilis kit contains the following:

1 ReadyPack® primary reagent pack containing ADVIA Centaur Syphilis Solid Phase Reagent (20 mL);
1 Ancillary pack containing ADVIA Centaur Syphilis Ancillary Reagent (10mL)
ADVIA Centaur Syphilis Master Curve card
2 vials of Syphilis Low Calibrator (2 mL fill volume)
2 vials of Syphilis High Calibrator (2 mL fill volume)
ADVIA Centaur Syphilis Calibrator Assigned Value cards

In addition Syphilis quality control materials (2 vials of negative control and 2 vials of positive control with 7 mL fill volume each) are provided separately.

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

Not Found

Intended User / Care Setting

Not Found

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

Precision: 5 serum based samples (serum sample pools), 3 plasma based samples (2 controls. low and high. and one additional plasma pool) and 2 calibrators (low and high) were tested in duplicate over the course of 20 days, two runs per day, for a total of 40 runs and 80 replicates.
Reproducibility: Two different reagent lots were used across three external sites. The protocol involves 10 days, 2 runs per day, and 4 replicates per run for sample pools, and 8 replicates per run for negative and positive control materials.
Interference: Three samples at syphilis levels (negative, low positive and high positive) were spiked with interferent to evaluate interference by endogenous substances.
Cross-reactivity:

211 cord blood samples, samples from pregnant women (15, 200, and 31d trimester), samples from hospitalized patients, pediatric samples and transplant samples were tested. Each sample was tested in singlicate using one lot of reagent on one system.
265 specimens from 20 groups of potential cross-reactant disease states were assayed. These samples had a known activity to the potential cross reactant in each group of specimens which was determined by FDA-cleared methods and provided by the respective vendor. Each sample was tested in singlicate using one lot of reagent.
Clinical evaluation: Samples from various patient populations were tested at three clinical trial sites. Total n=2108, n=561 expected positive population, n=741 samples sent for syphilis testing.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision:

Calibrator High (plasma) (high positive): Mean (Index) 8.16, Total CV 3.69%
Calibrator Low (plasma) (high negative): Mean (Index) 0.68, Total CV 3.32%
Control Negative (plasma) (low negative): Mean (Index) 0.11, Total SD 0.01
Control Positive (plasma) (moderate pos.): Mean (Index) 3.84, Total CV 3.69%
Plasma sample (moderate positive): Mean (Index) 1.99, Total CV 3.43%
Serum sample 1 (low negative): Mean (Index) 0.19, Total SD 0.01
Serum sample 2 (high negative): Mean (Index) 0.80, Total CV 3.20%
Serum sample 3 (low positive): Mean (Index) 1.28, Total CV 3.22%
Serum sample 4 (high positive): Mean (Index) 6.96, Total CV 4.02%
Serum sample 5 (high positive): Mean (Index) 21.45, Total CV 4.20%
Reproducibility: (Pooled across 3 Sites for a representative reagent lot)
Negative Control (plasma) (low negative): Mean 0.11, Total SD 0.01%
Serum Pool 1 (low negative): Mean 0.18, Total SD 0.01%
Serum Pool 2 (high negative): Mean 0.75, Total CV 2.3%
Serum Pool 3 (low positive): Mean 1.20, Total CV 2.4%
Serum Pool 4 (high positive): Mean 6.67, Total CV 2.5%
Serum Pool 5 (high positive): Mean 20.42, Total CV 2.6%
Positive Control (plasma) (moderate positive): Mean 3.56, Total CV 2.5%
Interference: No indication of interference up to the levels claimed including Hemoglobin (500 mg/dL), Conjugated Bilirubin (40 mg/dL), Unconjugated Bilirubin (40 mg/dL), Intralipid (1000 mg/dL), Cholesterol, Total (400 mg/dL), Gamma Globulin (60 mg/dL), Protein, Total (HSA) (11 g/dL), Biotin (500 ng/mL). For Syphilis positive samples, all results showed

Regulation Number and Section

§ 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).

Summary

0

510(k) Summary of Safety and Effectiveness for the

ADVIA® Centaur Syphilis Assay

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.

A. 510(k) Number:

B. Date of Preparation: November 1, 2011

C. Proprietarv and Established Names:

ADVIA® Centaur Syphilis Assay ADVIA® Centaur Syphilis Quality Control Materials

D. Applicant:

Siemens Healthcare Diagnostics Inc., 511 Benedict Ave, Tarrytown, NY 10591 Kira Gordon, Sr. Regulatory Affairs Specialist Office: (914) 524-2996 Fax: (914) 524-2500

E. Regulatory Information:

ADVIA® Centaur Syphilis Assay (reagents and calibrators)

1. Regulation section: 21 CFR § 866.3830 Treponema pallidum treponemal test reagents
1. Classification: Class II
1. Product Code: LIP, enzyme linked immunoabsorption assay, treponema pallidum
1. Panel: Microbiology

ADVIA® Centaur Syphilis Quality Control Materials

1. Regulation section: 21 CFR § 862.1660
  Quality control material (assayed and unassayed).
1. Classification: Class I-
1. Product Code: MJY; Kit, serological, negative control

MJX; Kit, serological, positive control

1. Panel: Microbiology

F. Predicate Device:

ADVIA® Centaur Syphilis Assay (reagents and calibrators) and ADVIA® Centaur Syphilis Quality Control Materials are substantially equivalent to the IMMULITE 2000 Syphilis Screen Test System cleared under K091361

G. Device Description:

The ADVIA Centaur syphilis assay is a fully automated, antigen sandwich assay, using direct chemiluminometric technology. The ancillary pack reagent containing acridinium-ester-labeled T. pallidum recombinant antigens is added to the sample.

1

These T. pallidum antigens complex with the antibodies in the sample. The solid phase containing biotinylated T. pallidum recombinant antigens preformed to streptavidin-coated magnetic latex particles, is then added to the sample. These particles capture the T. pallidum antigen-antibody complexes. Antibody-antigen complexes will form if Syphilis antibodies are present in the sample. A direct relationship exists between the level of antibodies to T. pallidum present in the patient sample and the amount of relative light units (RLUs) detected by the system. A result of reactive, nonreactive, or equivocal is determined according to the Index Value established with the calibrators.

The Syphilis kit contains the following:

1 ReadyPack® primary reagent pack containing ADVIA Centaur Syphilis Solid Phase Reagent (20 mL);
1 Ancillary pack containing ADVIA Centaur Syphilis Ancillary Reagent (10mL)
ADVIA Centaur Syphilis Master Curve card
2 vials of Syphilis Low Calibrator (2 mL fill volume)
2 vials of Syphilis High Calibrator (2 mL fill volume)
ADVIA Centaur Syphilis Calibrator Assigned Value cards

In addition Syphilis quality control materials (2 vials of negative control and 2 vials of positive control with 7 mL fill volume each) are provided separately.

H. Intended Use:

The ADVIA Centaur Syphilis (SYPH) assay is an in-vitro diagnostics immunoassay for the qualitative determination of antibodies to Treponema pallidum in human serum or plasma (EDTA. lithium or sodium heparinized, citrate) using the ADVIA Centaur® and ADVIA Centaur® XP systems as an aid in the diagnosis of syphilis. The ADVIA Centaur Syphilis assay is not intended for blood and tissue donor screening.

ADVIA® Centaur Syphilis Quality Control Materials are for in-vitro diagnostics use to monitor the performance of the Syphilis assay on the ADVIA Centaur® systems. The performance of the SYPH quality control material has not been established with any other Syphilis assay.

I. Substantial Equivalence Information:

Both the predicate device and ADVIA Centaur Syphilis assay employ prepackaged reagents, calibrators and controls for use on automated test systems. A comparison of the important similarities and differences of these assays is provided in the following table:

Item	New Device:	Predicate Device:
Analyte	antibodies to Treponema pallidum	Same
Intended Use	For in vitro diagnostic use in the	Same

2

| | qualitative determination of
antibodies to Treponema pallidum | |
|---------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------|
| Measurement | qualitative | Same |
| Assay type | direct sandwich immunoassay based
on chemiluminescent technology | Enzyme labeled, one-step
chemiluminescent immunoassay |
| Sample type | Serum , Heparinized Plasma, EDTA
plasma, citrate plasma | Serum , Heparinized Plasma |
| Instrument to be
used | ADVIA Centaur | IMMULITE 2000 |
| Capture/Detection
Antigen/Antibody | Reagent: recombinant antigens
TpN17 and TpN15 as biotin
conjugates
Ancillary pack: recombinant
antigens TpN17 and TpN15 as
acridinium ester conjugates | Beads coated with purified
recombinant antigen TpN17 are
linked to enzyme conjugated
purified recombinant TpN17
antigen in the reagent. |
| Cut-Offs | 1.1 Reactive | 0.9 to 1.1 Reactive |
| Sample Volume | 100 µL | 100 µL |
| Interference | Not affected by hemolysis, icterus or
lipemia at test levels | Not affected by hemolysis, icterus
or lipemia at test levels |
| Hook Effect | None observed | None observed |
| Use of Calibrators | Yes | Yes |
| Calibrators matrix | Human plasma | Human serum |
| Number of
calibrators | two | one |
| Calibrator fill
volume | Liquid, 2 mL | Lyophilized, 4 mL |
| Use of controls | Yes | Yes |
| Number of controls | two | two |
| Control matrix | Human plasma | Human serum |
| Control fill volume | Liquid, 7 mL | Lyophilized, 6 mL |

J. Performance Characteristics

Substantial equivalence was demonstrated by testing several performance characteristics including imprecision, reproducibility, interfering and cross-reactive substances.

a.Precision

Precision estimates were computed according to CLSI document EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. Within run and total imprecision were evaluated by testing 5 serum based samples (serum sample pools), 3 plasma based samples (2 controls. low and high. and one additional plasma pool) and 2 calibrators (low and high). The elevated levels were spiked with syphilis antigen to achieve appropriate concentrations. The samples were assayed in duplicate over the course of 20 days, two runs per day, for a total of 40 runs and 80 replicates.

3

| Pool | #
Repl. | Mean
(Index) | Within Run | | Between
Run | | Between
Day | | Total | |
|----------------------------------------------|------------|-----------------|------------|------|----------------|------|----------------|------|-------|------|
| | | | SD | CV | SD | CV | SD | CV | SD | CV |
| Calibrator High (plasma)
(high positive) | 80 | 8.16 | 0.14 | 1.67 | 0.06 | 0.78 | 0.26 | 3.20 | 0.30 | 3.69 |
| Calibrator Low (plasma)
(high negative) | 80 | 0.68 | 0.01 | 1.81 | 0.01 | 0.83 | 0.02 | 2.65 | 0.02 | 3.32 |
| Control Negative (plasma)
(low negative) | 80 | 0.11 | 0.00 | NA | 0.00 | NA | 0.00 | NA | 0.01 | NA |
| Control Positive (plasma)
(moderate pos.) | 80 | 3.84 | 0.06 | 1.50 | 0.04 | 0.99 | 0.12 | 3.22 | 0.14 | 3.69 |
| Plasma sample (moderate positive) | 80 | 1.99 | 0.03 | 1.44 | 0.02 | 1.05 | 0.06 | 2.93 | 0.07 | 3.43 |
| Serum sample 1 (low negative) | 80 | 0.19 | 0.00 | NA | 0.00 | NA | 0.00 | NA | 0.01 | NA |
| Serum sample 2 (high negative) | 80 | 0.80 | 0.01 | 1.16 | 0.01 | 0.86 | 0.02 | 2.86 | 0.03 | 3.20 |
| Serum sample 3 (low positive) | 80 | 1.28 | 0.02 | 1.31 | 0.01 | 0.93 | 0.04 | 2.79 | 0.04 | 3.22 |
| Serum sample 4 (high positive) | 80 | 6.96 | 0.10 | 1.45 | 0.07 | 0.95 | 0.25 | 3.63 | 0.28 | 4.02 |
| Serum sample 5 (high positive) | 80 | 21.45 | 0.41 | 1.93 | 0.28 | 1.29 | 0.75 | 3.50 | 0.90 | 4.20 |

b.Reproducibility

The reproducibility study was conducted using two different reagent lots at three external sites. The protocol was run over 10 days, 2 runs per day, and 4 replicates per run for the sample pools, and 8 replicates per run for the negative and positive control materials. Reproducibility data pooled across 3 Sites, data is presented separately for a representative reagent lot.

| | #
Repl. | Mean | Within Run | | Between Run | | Between
Day | | Total | |
|--------------------------------------------------|------------|-------|------------|-----|-------------|-----|----------------|-----|-------|-----|
| Pool | | | SD | CV | SD | CV | SD | CV | SD | CV |
| Negative Control (plasma)
(low negative) | 480 | 0.11 | 0.004 | NA | 0.002 | NA | 0.01 | NA | 0.01 | NA |
| Serum Pool 1 (low negative) | 240 | 0.18 | 0.006 | NA | 0.002 | NA | 0.01 | NA | 0.01 | NA |
| Serum Pool 2 (high negative) | 240 | 0.75 | 0.01 | 1.3 | 0.01 | 1.4 | 0.01 | 1.3 | 0.02 | 2.3 |
| Serum Pool 3 (low positive) | 240 | 1.20 | 0.02 | 1.5 | 0.02 | 1.4 | 0.01 | 1.2 | 0.03 | 2.4 |
| Serum Pool 4 (high positive) | 240 | 6.67 | 0.10 | 1.5 | 0.11 | 1.6 | 0.08 | 1.2 | 0.17 | 2.5 |
| Serum Pool 5 (high positive) | 240 | 20.42 | 0.29 | 1.4 | 0.31 | 1.5 | 0.31 | 1.5 | 0.53 | 2.6 |
| Positive Control (plasma)
(moderate positive) | 480 | 3.56 | 0.06 | 1.6 | 0.04 | 1.2 | 0.05 | 1.4 | 0.09 | 2.5 |

c.Interference

Interference by endogenous substances in the ADVIA Centaur Syphilis assay was evaluated at three syphilis levels (negative, low positive and high positive) using a significance criterion of >10% variance from the control. Each serum pool was spiked with an interferent to the levels indicated in the table below.

Interferent	Tested concentration (up to)
Hemoglobin	500 mg/dL
Conjugated Bilirubin	40 mg/dL
Unconjugated Bilirubin	40 mg/dL
Intralipid	1000 mg/dL

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Cholesterol, Total	400 mg/dL
Gamma Globulin	60 mg/dL
Protein, Total (HSA)	11 g/dL
Biotin	500 ng/mL

There was no indication of interference up to the levels claimed.

For the Syphilis positive samples all results demonstrated