DIASORIN LIAISON TREPONEMA ASSAY

K061247 · DiaSorin, Inc. · LIP · Jul 31, 2006 · Microbiology

Device Facts

• Record ID: K061247
• Device Name: DIASORIN LIAISON TREPONEMA ASSAY
• Applicant: DiaSorin, Inc.
• Product Code: LIP · Microbiology
• Decision Date: Jul 31, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3830
• Device Class: Class 2

Intended Use

The LIAISON® Treponema assay uses chemiluminiscence immunoassay (CLIA) technology for the qualitative detection of total antibodies of any class (IgG/IgM) directed against Treponema pallidum in human serum. The presence of antibodies to Treponema pallidum specific antigen, in conjunction with non treponemanal laboratory tests and clinical findings, may aid in the diagnosis of syphilis infection. The LIAISON® Treponema assay is not intended for use in screening blood or plasma donors.

Device Story

The LIAISON® Treponema Assay is a one-step chemiluminescence immunoassay (CLIA) performed on the LIAISON® Analyzer. It detects total antibodies (IgG/IgM) against Treponema pallidum in human serum. Recombinant T. pallidum antigens coat magnetic particles (solid phase) and are linked to an isoluminol derivative (tracer). Patient samples, calibrators, or controls are incubated with the solid phase; antibodies bind to the antigen-coated particles. After washing, starter reagents induce a flash chemiluminescence reaction. A photomultiplier measures the light signal (Relative Light Units, RLU), which is proportional to the amount of antibody present. The assay is used in clinical laboratories by trained personnel to aid in syphilis diagnosis, either as a screening test or a confirmatory test depending on the clinical algorithm. Results assist clinicians in diagnosing syphilis infection when combined with non-treponemal tests and clinical findings.

Clinical Evidence

Clinical performance evaluated via method comparison against predicate (CAPTIA™ Syphilis-G) across 3 US sites and European sites. Study populations included medically diagnosed syphilis (n=51 US, n=127 EU), routine lab samples (n=999), HIV+ (n=200), pregnancy (n=200), and healthy adults (n=992). Overall percent agreement varied by population (e.g., 94.1% for diagnosed syphilis, 93.2% for routine lab). Discordant samples were resolved using additional testing (RPR/TP-PA). Analytical studies included precision (overall %CV 6.07-23.66%), cross-reactivity (244 samples tested), and interference (hemoglobin, bilirubin, triglycerides).

Technological Characteristics

Chemiluminescence immunoassay (CLIA). Solid phase: magnetic particles coated with recombinant Tp17 DNA antigen. Tracer: isoluminol-antigen conjugate. Energy source: flash chemiluminescence reaction measured by photomultiplier. Form factor: Reagent Integral (plastic container with compartments). Connectivity: Automated on LIAISON® Analyzer. Software: Automated processing of incubation, wash, and signal measurement. Storage: 2-8°C.

Indications for Use

Indicated for use in conjunction with nontreponemal laboratory tests and clinical findings to aid in the diagnosis of syphilis infection. Not for use in screening blood or plasma 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

• Trinity CAPTIA™ Syphilis (T. Pallidum) G (K014233)

Submission Summary (Full Text)

{0}------------------------------------------------

K061247
JUL 3 1 2006

# 510(k) SUMMARY

## SUBMITTED BY:

Carol A. DePouw Regulatory Affairs Specialist DiaSorin Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285 Phone [phone] Fax [phone] Email: [e-mail]

## NAME OF DEVICE:

| Trade Name: | DiaSorin LIAISON® Treponema Assay |
|----------------------------|----------------------------------------------------------------------------------------------------------------------------|
| Common Names/Descriptions: | Immunoassay for the detection of antibodies to<br>Treponema pallidum to aid in the diagnosis of<br>Syphilis in human serum |
| Classification Names: | Treponema pallidum treponemal test reagents |
| Product Code: | LIP |
| | Trinity CAPTIA™ Syphilis (T. Pallidum) G<br>(K014233) |

## DEVICE DESCRIPTION:

PRE

INTENDED USE: The LIAISON® Treponema assay uses chemiluminescence immunoassay (CLIA) technology for the qualitative detection of total antibodies of any class (IqG/IqM) directed against Treponema pallidum in human serum.

The presence of antibodies to Treponema pallidum specific antigen, in conjunction with non treponemal laboratory tests and clinical findings, may aid in the diagnosis of syphilis infection.

## The LIAISON® Treponema Assay is not intended for use in screening blood or plasma donors.

KIT DESCRIPTION: The method for determination of specific total antibodies to Treponema pallidum is a one-step chemiluminescence immunoassay (CLIA).

All assay steps and incubations are performed by the LIAISON® Analyzer, with the exception of initial magnetic particle resuspension.

Recombinant antigens specific for Treponema pallidum are used for coating the magnetic particles (solid phase) and are used in the tracer when linked to an isoluminol derivative (isoluminol-antigen conjugate). During the incubation step antibodies present in the calibrators, samples or controls bind to the solid phase. The conjugate reacts

{1}------------------------------------------------

with the antibodies already bound to the solid phase. After the incubation, the unbound material is removed with a wash cycle.

Subsequently, the starter reagents are added and a flash Chemiluminescence reaction is induced. The light signal and hence the amount of isoluminol-antigen conjugate is measured by a photomultiplier as relative light units (RLU) and is indicative of total antibodies to Treponema pallidum present in calibrators, controls or samples,

### PERFORMANCE DATA:

Performance testing of the LIAISON® Treponema Assay for comparative clinical trials consisted of running selected samples for two (2) studies to support the intended use.

Study 1: Clinical Laboratory Screen Test (Treponemal Test followed by a Non-Treponemal test). This study consisted of samples from:

Medically Diagnosed Syphilis infection (Retrospective samples n=51 patients from the US and n =127 patients from Europe) Total n = 178.

Laboratory samples sent for Syphilis HIV Positive Samples (Prospective n=999) Pregnancy Samples (Prospective n=200)

Apparently Healthy Adults (Prospective n = 992)

Study 2: Diagnostic Confirmatory test (Traditional testing algorithm a non-treponemal test followed by a Treponemal test.) This study consists of: RPR/VDRL positive samples (Retrospective n=204).

COMPARATIVE CLINICAL TRIALS: The clinical trials were conducted at two external US laboratories and at DiaSorin,Inc. Testing was performed on prospective and retrospective samples as described in the two clinical studies above. The samples were tested by LIAISON® Treponema Assay and the comparator assay Trinity CAPTIA™ Syphilis (T.pallidum) G at the trial sites per the manufacturer's instructions for use. Discordant samples were further tested by RPR and TP-PA per the recommendations for non-treponemal testing and use of another treponemal method when following the algorithm to Screen for Syphilis: (Treponema Test as Screen) from (Use of Treponemal Tests to Screen for Syphilis, by Victoria Pope, PhD, Infect. Med 21 (8):399-404, 2004 Cliggottt Publishing Division of CMP Healthcare Media).

Image /page/1/Figure/11 description: This image is a flowchart that describes the process for testing for syphilis. The flowchart starts with an EIA test, and then branches out depending on the results. The flowchart includes tests such as the RPR test, TP-PA test, and FTA-ABS test. The flowchart also includes possible outcomes such as "Not syphilis", "Syphilis", and "Late latent or treated?"

{2}------------------------------------------------

# Study 1: Clinical Laboratory Screen Test

------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Medically Diagnosed Syphilis Infection – One Hundred Seventy-eight samples with different stages of syphilis. Fifty one of the samples were from the US and 127 were from Europe.

| | Percent Agreement | 95% Exact Confidence Interval |
|----------|--------------------|-------------------------------|
| Positive | 98.8%<br>(165/167) | 96.3 - 99.8% |
| Negative | 16.7%<br>(1/6) | 8.5-58.1% |
| Overall | 93.3%<br>(166/178) | 89.3 - 96.1% |

Samples sent to Laboratory for Syphilis testing – Nine Hundred Ninety-nine samples.

| Percent<br>Agreement | | 95% Exact Confidence Interval |
|----------------------|-----------------|-------------------------------|
| Positive | 55% (22/40) | 38.6 - 70.7% |
| Negative | 98.9% (909/919) | 98.0 - 99.5% |
| Overall | 93.2% (931/999) | 91.4 - 94.7% |

HIV positive samples – Two Hundred samples.

| | Percent<br>Agreement | 95% Exact Confidence Interval |
|----------|----------------------|-------------------------------|
| Positive | 75.8% (61/91) | 65.8 – 83.5% |
| Negative | 96.2% (100/104) | 90.4 - 98.9% |
| Overall | 84.5% (169/200) | 78.7 - 89.2% |

Pregnancy Samples - Two Hundred samples from pregnant women.

| | Percent | | |
|----------|-----------|-----------|-------------------------------|
| | Agreement | | 95% Exact Confidence Interval |
| Positive | 100% | (4/4) | 38.9 - 100% |
| Negative | 100% | (192/192) | 98.1 - 100% |
| Overall | 98.0% | (200/200) | 95.0 - 99.5% |

# Apparently Healthy Adults – Nine Hundred Ninety-two samples

| | Percent<br>Agreement | 95% Exact Confidence Interval |
|----------|----------------------|-------------------------------|
| Positive | 62.7% (54/86) | 51.7 – 73.0% |
| Negative | 99.3% (881/887) | 98.5 – 99.8% |
| Overall | 94.2% (935/992) | 92.6 – 95.6% |

{3}------------------------------------------------

# Study 2: Diagnostic Confirmatory Test

| | Percent Agreement | 95% Exact Confidence Interval |
|----------|-------------------|-------------------------------|
| Positive | 99.5% (200/201) | 98.2 - 100% |
| Negative | 100.0% (2/2) | 15.8 - 100% |
| Overall | 99.0% (202/204) | 97.3 - 100% |

RPR/VDRL Positive samples – Two Hundred four samples.

## Conclusion:

Study 1:

The LIAISON® Treponema Assay demonstrated overall agreement with the comparator kit following the Algorithm to Screen for Syphilis: Treponema test as Screen: Medically Diagnosed Syphilis Samples, 93.3% (95% Cl = 89.3 - 96.1%) Samples sent to the Laboratory for Syphilis testing, 93.2% (95% Cl = 91.4 - 94.7%) HIV positive samples, 84.5% (95% Cl = 78.7 – 89.2%) Pregnancy samples, 98.0% (95% CI = 95.0 - 99.5%) Apparently Healthy Adults, 94.2% (95% CI = 92.6 - 95.6%)

The results demonstrate that the LIAISON® Treponema Assay can be used with the LIAISON® Analyzer for the qualitative detection of total antibodies in human serum when used as a clinical diagnostic screening test (not intended for use with blood donors or for screening the general population).

## Study 2:

The LIAISON® Treponema Assay demonstrated overall agreement with the comparator kit for RPR/VDRL positive samples of 99.0% (95% Cl = 97.3 - 100%) when following the Traditional Algorithm: A non-treponemal test followed by a treponemal test.

The results demonstrate that the LIAISON® Treponema Assay can be used with the LIAISON® Analyzer for the qualitative detection of total antibodies in human serum when used as a diagnostic confirmatory test (not intended for use with blood donors

## Equivocal, repeat and resolution testing.

All equivocal results were repeated in duplicate on the Trinity CAPTIA™ Syphilis (T. Pallidum)-G kit and the LIAISON® Treponema assay per the respective package inserts. All samples that were positive on the Trinity CAPTIA ™ kit were also repeated in duplicate per the package insert. Samples that were discordant between the Trinity CAPTIA™ kit and the LIAISON® Treponema kit were tested further with a nontreponemal test (RPR) and with a treponemal kit capable of picking up total antibodies (TP-PA). The resolution of the discordants was carried out by following the Algorithm suggested by Victoria Pope Ph.D, as shown above, and the percent agreements for positive, negative and overall were recalculated.

{4}------------------------------------------------

Study 1 - Resolved: Medically Diagnosed Syphilis Samples, 97.7% (95% CI = 94.9 -- 99.2%) Samples sent to the Laboratory for Syphilis testing, 98.7% (95% Cl = 97.8 - 99.3%) HIV positive samples, 94.5% (95% Cl = 90.4 ~ 97.2%) Pregnancy samples, 100% (95% CI = 98.2 – 100%) Apparently Healthy Adults, 98.3% (95% CI = 97.3 - 99.0%)

Study 2 - Resolved:

RPR/VDRL positive samples, 100% (95% Cl = 98.2 - 100%)

{5}------------------------------------------------

REPRODUCIBILITY: Reproducibility studies were performed at 3 sites using a coded panel comprised of 9 "engineered" serum samples. The same coded panel samples were tested at all 3 sites. Samples were run in 4 replicates per run for 5 days. The results expressed for Index and RLU's are summarized in the tables below. Samples 1007 and 1008 were negative samples that read below the limit of the curve so Index values were nondetectable.

| sample<br>ID | N | mean<br>Index | within<br>run<br>%CV | between<br>run<br>%CV | total (by<br>site)<br>%CV | between<br>site<br>%CV | overall<br>%CV<br>Index | overall<br>sd<br>Index |
|--------------|----|---------------|----------------------|-----------------------|---------------------------|------------------------|-------------------------|------------------------|
| 1001 | 60 | 0.94 | 4.90 | 4.19 | 6.27 | 5.76 | 7.91 | 0.07 |
| 1002 | 60 | 1.07 | 2.86 | 3.99 | 4.82 | 4.54 | 6.07 | 0.06 |
| 1003 | 60 | 1.42 | 3.03 | 3.57 | 5.34 | 7.02 | 8.08 | 0.11 |
| 1004 | 60 | 0.95 | 3.86 | 3.60 | 4.97 | 6.76 | 7.43 | 0.07 |
| 1005 | 60 | 0.99 | 2.62 | 6.22 | 6.35 | 6.81 | 8.60 | 0.09 |
| 1006 | 58 | 1.26 | 1.89 | 3.93 | 4.19 | 6.70 | 6.93 | 0.09 |
| 1007 | 58 | ND | ND | ND | ND | ND | ND | ND |
| 1008 | 60 | ND | ND | ND | ND | ND | ND | ND |
| 1009 | 60 | 13.13 | 3.11 | 3.75 | 5.45 | 4.87 | 6.93 | 0.91 |
| NC | 60 | 0.25 | 7.02 | 12.16 | 13.57 | 17.76 | 20.06 | 0.05 |
| PC | 60 | 5.06 | 2.70 | 4.94 | 4.78 | 5.76 | 7.28 | 0.37 |

#### Reproducibility Index

#### Reproducibility RLU

| sample<br>ID | N | mean<br>RLU | within<br>run<br>%CV | between<br>run<br>%CV | total (by<br>site)<br>%CV | between<br>site<br>%CV | overall<br>%CV<br>RLU | overall<br>sd<br>RLU |
|--------------|----|-------------|----------------------|-----------------------|---------------------------|------------------------|-----------------------|----------------------|
| 1001 | 60 | 7845 | 4.72 | 4.31 | 6.41 | 5.52 | 7.87 | 617 |
| 1002 | 60 | 8901 | 2.70 | 3.95 | 4.82 | 4.55 | 6.07 | 540 |
| 1003 | 60 | 11873 | 1.94 | 4.52 | 5.75 | 7.58 | 8.76 | 1040 |
| 1004 | 60 | 7934 | 3.65 | 4.27 | 5.32 | 6.72 | 6.98 | 605 |
| 1005 | 60 | 8320 | 2.49 | 7.08 | 7.08 | 6.60 | 9.34 | 777 |
| 1006 | 58 | 10550 | 1.97 | 5.02 | 5.21 | 7.51 | 8.23 | 868 |
| 1007 | 58 | 1051 | 7.78 | 5.91 | 9.40 | 13.65 | 14.87 | 157 |
| 1008 | 60 | 1047 | 11.17 | 8.95 | 20.02 | 4.32 | 23.66 | 248 |
| 1009 | 60 | 105839 | 2.98 | 4.77 | 5.57 | 8.81 | 9.24 | 9778 |
| NC | 60 | 2027 | 6.19 | 6.19 | 9.26 | 16.04 | 15.94 | 323 |
| PC | 60 | 40799 | 3.44 | 4.95 | 5.89 | 10.84 | 10.70 | 4365 |

## Conclusion:

The material submitted in this premarket notification supports a substantial equivalence claim. The labelling is sufficient and satisfies the requirements of 21CFR 809 10

{6}------------------------------------------------

Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three lines representing its body and wings. The eagle is facing right. The logo is surrounded by a circular border with the words "U.S. Department of Health and Human Services" written around it.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Carol A. DePouw Regulatory Affairs Specialist DiaSorin, Inc. 1951 Northwestern Avenue P.O. Box 285 Stillwater, MN 55082-0285

JUL 3 1 2006

Re: k061247

> Trade/Device Name: DiaSorin LIAISON® Treponema Assay Regulation Number: 21 CFR § 866.3830 Regulation Name: Enzyme-linked immunoabsorption assay, Treponema pallidum Regulatory Class: II Product Code: LIP Dated: July 21, 2006 Received: July 24, 2006

Dear Ms. DePouw:

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 iddictions 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 in microa in the devices that have been reclassified in accordance with the provisions of the Federal Food, Drig and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, isting of devices, good manufacturing practice, labeling, and prohibitions against misburanting and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal D2-: ' in a

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 medion wour not not incant or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(() rems rket notification. The FDA finding of substantial equivalence of your device to a logal y marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

{7}------------------------------------------------

This letter will allow you to begin marketing your device as described in your Section 510(k) This setter will and w your to ough finding of substantial equivalence of your device to a legally premained newice results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, r you don't on the promotion and advertising of your device, please contact the Office of In of quostions on and proce Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). regulation entition on your responsibilities under the Act may be obtained from the Other general mionnation turers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sally, attorn

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{8}------------------------------------------------

#### 4.0 INDICATIONS FOR USE

510(k) Number (if known): K061247

Device Name: LIAISON® Treponema Assay

Indications for Use: The LIAISON® Treponema Assay and the LIAISON® Treponema Serum Controls uses chemiluminescence immunoassay (CLIA) technology for the qualitative detection of total antibodies of any class (IqG/IgM) directed against Treponema pallidum in human serum. The presence of antibodies to Treponema pallidum specific antigen, in conjunction with nontreponemal laboratory tests and clinical findings, may aid in the diagnosis of syphilis infection. The LIAISON® Treponema Assay is not intended for use in the screening of blood or plasma donors.

Prescription Use: X (Part 21 CFR 801 Subpart D) AND/OR

Over-the-Counter Use: (Part 21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation

Luddite Park

Division Sign-On

Office of in Vitro Diagnosuc Device Fivaluation and Safer

Section 4

K061247

Page 4 - 1