Elecsys Syphilis

K211302 · Roche Diagnostics · LIP · Jul 20, 2021 · Microbiology

Device Facts

• Record ID: K211302
• Device Name: Elecsys Syphilis
• Applicant: Roche Diagnostics
• Product Code: LIP · Microbiology
• Decision Date: Jul 20, 2021
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3830
• Device Class: Class 2

Indications for Use

Immunoassay for the in vitro qualitative detection of total antibodies (IgG and 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.

Device Story

Fully automated electrochemiluminescence immunoassay (ECLIA) for detection of anti-T. pallidum antibodies in human serum/plasma; uses double antigen sandwich format. Recombinant T. pallidum antigens labeled with biotin or ruthenium bind to patient IgG/IgM; complex captured by streptavidin-coated microparticles on electrode surface. Voltage application induces chemiluminescent emission measured by photomultiplier. Signal proportional to antibody concentration; compared to cutoff index (COI) to determine reactive/nonreactive status. Used in clinical laboratory settings on cobas e 801 analyzers. Results interpreted by clinicians alongside clinical symptoms and other serologic tests to diagnose syphilis. Modification improves biotin tolerance to 1200 ng/mL.

Clinical Evidence

Bench testing only. Performance verified via precision studies (CLSI EP05-A3), biotin interference (CLSI EP07-A3), matrix comparison, and stability studies. Method comparison using 232 clinical samples demonstrated positive and negative agreement between the updated and predicate assays. No clinical diagnostic trials were required for this modification.

Technological Characteristics

Double antigen sandwich immunoassay; electrochemiluminescence (ECLIA) detection. Reagents: biotinylated/ruthenium-labeled recombinant T. pallidum antigens, streptavidin-coated microparticles. Instrument: cobas e 801. Biotin tolerance: ≤ 1200 ng/mL. Calibration: 2-point. Qualitative output.

Indications for Use

Indicated for the qualitative detection of total antibodies (IgG and IgM) to Treponema pallidum in human serum and plasma as an aid in the diagnosis of syphilis infection. Not for use in screening blood or tissue donors.

Regulatory Classification

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), the Treponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies to Treponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genus Treponema and provides epidemiological information on syphilis.

Predicate Devices

• Elecsys Syphilis (K160910)

Submission Summary (Full Text)

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FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K211302

B Applicant

Roche Diagnostics

C Proprietary and Established Names

Elecsys Syphilis

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| LIP | Class II | 21 CFR 866.3830 - Treponema Pallidum
Treponemal Test Reagents | MI - Microbiology |

## II Submission/Device Overview:

A Purpose for Submission:

Market clearance for a previously cleared assay to detect antibodies to *T. pallidum* in human serum and plasma that has been modified to improve tolerance to elevated levels of biotin.

B Measurand:

Antibodies to *T. pallidum* (IgM and IgG)

C Type of Test:

A qualitative double antigen sandwich electrochemiluminescence immunoassay.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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## III Intended Use/Indications for Use:

### A Intended Use(s):

Immunoassay for the in vitro qualitative detection of total antibodies (IgG and 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.

### B Indication(s) for Use:

Same as Intended Use

### C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

### D Special Instrument Requirements:

For use with the cobas e 801.

## IV Device/System Characteristics:

### A Device Description:

The Elecsys Syphilis immunoassay is a fully automated, qualitative assay that uses a double antigen sandwich format for the detection of IgM and IgG antibodies to *T. pallidum* (TP). Recombinant *T. pallidum* antigens labeled with either biotin or a ruthenium complex bind to *T. pallidum*-specific IgG or IgM to form a double antigen sandwich complex. The sandwich complex binds to streptavidin-coated microparticles which can be immobilized magnetically to the surface of an electrode. Unbound substances are removed during a wash step using ProCell. A chemiluminescent substrate is then added to the reaction tube. Application of a voltage to the electrode induces a chemiluminescent emission which is measured by a photomultiplier.

The presence or absence of anti-TP antibodies in the specimen is determined by comparing the chemiluminescent signal in the reaction to the cutoff index (COI) determined from an active calibration. The strength of the signal generated is proportional to the amount of bound enzyme and thus the amount of anti-*T. pallidum* antibodies present in the specimen. If the chemiluminescent signal in the reaction is greater than or equal to the cutoff signal, the specimen is considered reactive for anti-TP antibodies. If the chemiluminescent signal is below the cutoff signal, the specimen is considered nonreactive for the anti-TP antibodies.

The results are reported out as follows:

COI ≥ 1.00 Reactive
COI < 1.00 Nonreactive

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Interpretation of results:

Reactive
Reactive for treponemal antibodies

Nonreactive
Nonreactive for treponemal antibodies

Test results are intended to aid in diagnosis only. As with all serological tests for syphilis, results should always be interpreted in conjunction with additional treponemal or non-treponemal serologic test results (as appropriate), the patient’s clinical symptoms, medical history, and other clinical and/or laboratory findings to produce a diagnosis of syphilis by disease stage.

All initially reactive samples should be retested in duplicate with the Elecsys Syphilis assay. If cutoff index values < 1.00 are found in both cases, the samples are considered negative for anti-Treponema pallidum antibodies.

Initially reactive samples with cutoff index values of ≥ 1.00 in either of the retests are considered repeatedly reactive. Repeatedly reactive samples must be confirmed according to recommended confirmatory algorithms.

The PreciControl Syphilis 1 and 2 controls and Syphilis Cal1 and Cal2 calibrators are for use with the Elecsys Syphilis Assay.

## B Principle of Operation:

This is a fully automated electrochemiluminescence immunoassay.

## V Substantial Equivalence Information:

## A Predicate Device Name(s):

Elecsys Syphilis

## B Predicate 510(k) Number(s):

K160910

## C Comparison with Predicate(s):

| Device & Predicate Device(s): | K211302 | K160910 | Change Description |
| --- | --- | --- | --- |
| Device Trade Name | Elecsys Syphilis | Elecsys Syphilis | |
| General Device Characteristic Similarities | | | |
| Intended Use/Indications For Use | Same | Immunoassay for the in vitro qualitative detection of total antibodies (IgG and IgM) to Treponema pallidum in human serum | |

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| | | 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. | N/A |
| --- | --- | --- | --- |
| Assay Method | Same | Double antigen sandwich assay | N/A |
| Detection Method | Same | Electrochemiluminescence (ECLIA) | N/A |
| Instrument Platform | cobas e 801 | cobas e 411, e 601, e 602, and e 801 | Initially limited to use on the cobas e 801 analyzer |
| Test Time | Same | 18 minutes | N/A |
| Test Type | Same | Qualitative | N/A |
| Specimen matricies | Same | Serum, Li-heparin, Na-heparin, K2-EDTA, K3-EDTA, CPDA and Na-citrate plasma | N/A |
| General Device Characteristic Differences | | | |
| Biotin Tolerance | ≤ 1200 ng/mL | ≤ 60 ng/mL | Modification of reagents to improve tolerance to elevated levels of biotin. |

VI Standards/Guidance Documents Referenced:

Deciding When to Submit a 510(k) for a Change to an Existing Device: Guidance for Industry and Food and Drug Administration Staff

Refuse to Accept Policy for 510(k)s: Guidance for Industry and Food and Drug Administration Staff

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VII Performance Characteristics (if/when applicable):

A Analytical Performance:

A limited number of studies were conducted to verify the assay performance cleared under K160910 was not affected by the changes made to improve tolerance to elevated levels of biotin.

1. Internal Precision:

The precision of the Elecsys Syphilis assay was evaluated in an internal study using seven human serum samples, the PreciControl 1 and PreciControl 2 controls, and one lot of reagent. Two replicates of each serum sample and control were tested two times per day for 21 days. Human serum samples were prepared to create a panel of two negative samples (COI < 1.0), one low positive samples (COI approximately = 1.0), and four positive samples (COI > 1.0). The mean COI value, Repeatability Standard Deviation (SD) and percent coefficient of variation (%CV) as well as Intermediate Precision SD and %CV were calculated for each group of samples. A summary of the results is shown below.

| | | Repeatability | | Intermediate precision | | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | Mean [COI] | SD [COI] | CV [%] (UCL* 95%) | SD [COI] | CV [%] (UCL* 95%) | n |
| Human serum 1 | 0.125 | 0.00192 | 1.5 (1.9) | 0.00210 | 1.7 (1.9) | 84 |
| Human serum 2 | 0.888 | 0.0175 | 2.0 (2.4) | 0.0264 | 3.0 (3.5) | 84 |
| Human Serum 3 | 1.09 | 0.0173 | 1.6 (1.9) | 0.0260 | 2.4 (2.9) | 84 |
| Human Serum 4 | 4.11 | 0.0983 | 2.4 (2.9) | 0.126 | 3.1 (3.6) | 84 |
| Human Serum 5 | 6.88 | 0.198 | 2.9 (3.5) | 0.249 | 3.6 (4.3) | 84 |
| Human Serum 6 | 15.8 | 0.395 | 2.5 (3.0) | 0.574 | 3.6 (4.3) | 84 |
| Human Serum 7 | 16.4 | 0.395 | 2.4 (2.9) | 0.540 | 3.3 (3.9) | 84 |
| PreciControl 1 | 0.0951 | 0.00107 | 1.1 (1.4) | 0.00130 | 1.4 (1.6) | 84 |
| PreciControl 2 | 5.90 | 0.126 | 2.1 (2.6) | 0.155 | 2.6 (3.0) | 84 |

*Upper Confidence Limit

Multi-site Reproducibility:

See K160910

2. Linearity:

Not applicable; this is a qualitative assay.

3. Analytical Specificity/Interference:

Potential interference with specimens containing biotin was evaluated by testing three anti-T. pallidum antibody concentrations (negative, near cut-off and positive). One aliquot of each serum sample was spiked with the interfering substance (biotin), another aliquot was spiked with the same volume of the respective solvent (dilution pool). The interfering pool was then incrementally diluted into the dilution pool. The recovery for each sample was calculated by comparison to the analyte concentration of the respective dilution pools.

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The results of the study support the following statement in the assay labeling:
Specimens that contain biotin at a concentration of 1200 ng/mL demonstrate less than or equal to 10 % negative bias in COI values.
For complete endogenous substances interference study results see K160910.

4. Assay Reportable Range:
See K160910

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
The claimed on-board reagent stability and calibration frequency reported in K160910 was confirmed with new studies.

6. Detection Limit:
See K160910

7. Assay Cut-Off:
See K160910

## B Comparison Studies:

1. Method Comparison with Predicate Device:
A method comparison study was conducted to confirm the modified assay yields equivalent performance compared to the unmodified assay. The results obtained from 232 samples distributed across the span of the reportable range were measured internally with one reagent lot of the current assay and three different reagent lots of the updated assay in single determination. The study showed 100% agreement of the qualitative results and regression analysis of the COI values demonstrated acceptable concordance between the assays. The results of the original method comparison study are found in K160910.

2. Matrix Comparison:
See K160910

## C Clinical Studies:

1. Clinical Sensitivity:
See K160910

2. Clinical Specificity:
See K160910

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
See K160910

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D Clinical Cut-Off:
Not applicable

E Expected Values/Reference Range:
See K160910

VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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