IMMULITE 2000 SYPHILIS SCREEN TEST SYSTEM

K091361 · Siemens Healthcare Diagnostics · LIP · Dec 16, 2009 · Microbiology

Device Facts

• Record ID: K091361
• Device Name: IMMULITE 2000 SYPHILIS SCREEN TEST SYSTEM
• Applicant: Siemens Healthcare Diagnostics
• Product Code: LIP · Microbiology
• Decision Date: Dec 16, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3830
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

The Immulite 2000 syphilis screen test is a treponemal testing procedure for the qualitative detection of antibodies to Treponema pallidum in human serum or heparinized plasma on the Immulite 2000 analyzer as an aid in the diagnosis of syphilis. The Immulite 2000 syphilis screen is not intended for use in screening blood or plasma donors.

Device Story

Solid-phase, one-step chemiluminescent immunoassay; utilizes beads coated with biotinylated recombinant Treponema pallidum p17 (Tp17) antigen. Patient sample and reagent incubated with bead; total antibodies form antigen sandwich complex with biotinylated Tp17 on bead and enzyme-conjugated Tp17 in reagent. Centrifugal washes remove unbound components; chemiluminescent substrate added. Signal generated proportional to bound enzyme. Performed on IMMULITE 2000 analyzer in clinical laboratory settings. Output is qualitative result (Reactive, Indeterminate, Non-reactive) based on signal ratio to adjustor curve parameter. Aids clinicians in syphilis diagnosis when used with clinical findings and non-treponemal tests.

Clinical Evidence

Clinical study compared IMMULITE 2000 Syphilis Screen against LIAISON Treponema Assay. Two cohorts: 281 medically diagnosed syphilis patients and 924 routine samples. In diagnosed patients, positive agreement 99.3% (97.4-99.9% CI), negative agreement 75% (34.9-96.8% CI), overall 98.2%. In routine samples, positive agreement 99.4% (98.0-99.9% CI), negative agreement 99.1% (97.9-99.7% CI), overall 99.2%. Precision/reproducibility between-site CVs ranged from 6.1% to 29.7%.

Technological Characteristics

Solid-phase, one-step chemiluminescent enzyme immunoassay. Components: beads coated with recombinant T. pallidum p17 (Tp17) antigen; alkaline phosphatase-conjugated Tp17 antigen. Instrument: Immulite 2000 Random Access Analyzer. Sample types: serum, heparinized plasma. Cut-off: ratio of sample signal to adjustor curve parameter P1 (≥1.1 Reactive, 0.9-<1.1 Indeterminate, <0.9 Non-reactive).

Indications for Use

Indicated for qualitative detection of Treponema pallidum antibodies in human serum or heparinized plasma to aid in syphilis diagnosis. Not for blood or plasma donor screening.

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

• DiaSorin Liaison® Treponema Assay (K061247)

Submission Summary (Full Text)

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K091361/

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# DEC 1 6 2009

| 510(k) Summary as Required by 21 CFR 807.92 | | | |
|---------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|--|
| Submitter: | Siemens Healthcare Diagnostics Inc.<br>5210 Pacific Concourse Drive<br>Los Angeles, CA 90045-6900 | | |
| Contact Person: | Robert C. Eusebio<br>Director Regulatory Affairs<br>1584 Enterprise Blvd<br>West Sacramento, CA 95691<br>[phone] | | |
| Date Prepared: | September 10, 2009 | | |
| Device Trade Name: | IMMULITE® 2000 Syphilis Screen | | |
| Common Name: | Immunoassay for Treponema pallidum<br>21 CFR 866.3830 | | |
| Substantial Equivalence: | K061247<br>DiaSorin LIASION® Treponema Assay | | |
| Device Description: | The IMMULITE 2000 Syphilis Screen is a solid-phase, one-<br>step chemiluminescent immunoassay. The solid phase (bead) is<br>coated with biotinylated recombinant Treponema pallidum p17<br>(Tp17) antigen. The liquid phase consists of alkaline<br>phosphatase (bovine calf intestine) conjugated to purified<br>recombinant Treponema pallidum p17 (Tp17) antigen. | | |
| | The patient sample and reagent are incubated together with the<br>coated bead for 30 minutes. During this time, total antibody to<br>Treponema pallidum in the sample forms an antigen sandwich<br>complex with biotinylated recombinant Treponema pallidum<br>pl 7 (Tp17) antigen on the bead and enzyme conjugated purified<br>recombinant Treponema pallidum p17 (Tp17) antigen in the<br>reagent. Unbound patient sample and enzyme conjugate are<br>then removed by centrifugal washes. Finally,<br>chemiluminescent substrate is added to the reaction tube<br>containing the bead and the signal is generated in proportion to<br>the bound enzyme. | | |

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| Intended Use: | The IMMULITE® 2000 Syphilis Screen test is a<br>treponemal testing procedure for the qualitative<br>detection of antibodies to Treponema pallidum in human<br>serum or heparinized plasma on the IMMULITE 2000<br>analyzer as an aid in the diagnosis of syphilis.<br><br>The IMMULITE 2000 Syphilis Screen is not intended<br>for use in screening blood or plasma donors. |
|------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Technological Aspects: | A comparison of the device features, intended use, laboratory<br>data and other information demonstrate that the IMMULITE®<br>2000 Syphilis Screen is substantially equivalent to the<br>currently marketed DiaSorin LIASION® Treponema Assay,<br>as summarized in the following tables. |

| | Table 1: Comparison of IMMULITE® with LIAISON® Assay |
|--|------------------------------------------------------|
| | |

| | IMMULITE 2000 | LIAISON |
|---------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | The IMMULITE® 2000 Syphilis<br>Screen test is a treponemal testing<br>procedure for the qualitative<br>detection of antibodies to Treponema<br>pallidum in human serum or<br>heparinized plasma on the<br>IMMULITE 2000 analyzer as an aid<br>in the diagnosis of syphilis.<br><br>The IMMULITE 2000 Syphilis<br>Screen is not intended for use in<br>screening blood or plasma donors. | The LIAISON Treponema assay uses<br>chemiluminescence immunoassay<br>(CLIA) technology for the qualitative<br>detection of total antibodies directed<br>against Treponema pallidum in<br>human serum. The presence of<br>antibodies to Treponema pallidum<br>specific antigen, in conjunction with<br>non-treponemal laboratory tests and<br>clinical findings, may aid in the<br>diagnosis of syphilis infection.<br><br>The LIAISON Treponema Assay is<br>not intended for use in screening<br>blood or plasma donors. |
| Assay Type | Enzyme labeled, one-step<br>chemiluminescent immunoassay | One-step sandwich chemiluminescent<br>immunoassay |
| Capture/Detection<br>Antigen/Antibody | Beads coated with purified<br>recombinant Treponema pallidum p17<br>(TpN17) antigens are linked to<br>enzyme conjugated purified<br>recombinant Treponema pallidum p17<br>antigen in the reagent. | Magnetic particles coated with Tp17<br>DNA recombinant protein specific for<br>Treponema pallidum are linked to an<br>isoluminol derivative (isoluminol-<br>antigen conjugate). |
| Cut-Offs | Test value = ratio of signal from<br>sample to that of signal of adjustor<br>curve parameter P1. | Index value = ratio of signal from<br>sample to that of the standard |
| | $\geq$ 1.1 Reactive<br>0.9 to $<$ 1.1 Indeterminate<br>$<$ 0.9 Non-reactive | $\geq$ 1.1 Positive<br>0.9 to $<$ 1.1 Equivocal<br>$<$ 0.9 Negative |
| Reportable Range | Qualitative Assay | Qualitative Assay |

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| | IMMULITE 2000 | LIAISON |
|------------------|-----------------------------------------------------------------|-----------------------------------------------------------------|
| Sample Volume | 100 µL (plus dead volume) | 220 µL (includes dead volume) |
| Cross-Reactivity | None observed with tested agents | None observed with tested organisms |
| Interference | Not affected by hemolysis, icterus or<br>lipemia at test levels | Not affected by hemolysis, icterus or<br>lipemia at test levels |
| Hook Effect | None observed | None observed |

As part of the clinical study, samples from various patient populations were tested with both the IMMULITE Syphilis Screen and the LIAISON Treponema Assay. Results are summarized in the following tables.

### Table 2: Method Comparison, Medically Diagnosed Syphilis Patients

| Medically Diagnosed Syphilis Patients | | | | |
|---------------------------------------|-------------------------|----------|----------|-------|
| | Liaison Treponema Assay | | | |
| Immulite Syphilis Assay | Equivocal | Negative | Positive | Total |
| Indeterminate | 0 | 0 | 2 | 2 |
| Non-Reactive | 0 | 6 | 0 | 6 |
| Reactive | 1 | 2 | 270 | 273 |
| Total | 1 | 8 | 272 | 281 |

| | | 95% Confidence Interval |
|---------------------|-----------------|-------------------------|
| Positive Agreement: | $270/272=99.3%$ | 97.4% - 99.9% |
| Negative Agreement: | $6/8=75%$ | 34.9% - 96.8% |
| Overall Agreement: | $276/281=98.2%$ | 95.9% - 99.4% |

## Table 3: Method Comparison, Samples Sent for Syphilis Testing

| Samples Sent for Routine Syphilis Testing | | | | |
|-------------------------------------------|-------------------------|----------|----------|-------|
| | Liaison Treponema Assay | | | |
| Immulite Syphilis Assay | Equivocal | Negative | Positive | Total |
| Indeterminate | 0 | 0 | 2 | 2 |
| Non-Reactive | 0 | 558 | 0 | 558 |
| Reactive | 0 | 5 | 359 | 364 |
| Total | 0 | 563 | 361 | 924 |

| | | 95% Confidence Interval |
|---------------------|-----------------|-------------------------|
| Positive Agreement: | $359/361=99.4%$ | 98.0% - 99.9% |
| Negative Agreement: | $558/563=99.1%$ | 97.9% - 99.7% |
| Overall Agreement: | $917/924=99.2%$ | 98.4% - 99.7% |

Precision/ reproducibility information in the product insert for the LIAISON Treponema Assay shows between-site coefficients of variation (CV) ranging from 4.32% to 17.76% for the 11 samples reported. The reproducibility of the IMMULITE Syphilis Screen as measured by between-site CV ranged from 7.1% to 22.6% for Lot 1 and from 6.1% to 29.7% for Lot 2. Seven samples were tested with both IMMULITE lots.

A comparison of the device features, intended use, laboratory data and other information demonstrates that the IMMULITE® 2000 Syphilis Screen is substantially equivalent to the currently marketed DiaSorin LIASION® Treponema assay.

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

DEC 1 8 2009

Ms. Carolyn K. George C/o Independent Consultant Siemens Healthcare Diagnostics 6695 River Crest Point Suwanee, Georgia 30024

Re: k091361

Trade/Device Name: IMMULITE® 2000 Syphilis Screen Regulation Number: 21 CFR § 866.3830 Regulation Name: Treponema pallidum treponemal test reagents Regulatory Class: II Product Code: LIP Dated: September 10, 2009 Received: September 14, 2009

Dear Ms. George:

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 (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, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding 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 vour 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 Register.

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#### Page 2- Carolyn George

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 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(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device 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, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Salazarpena

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

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## Indications for Use Form

510(k) Number (if known): K091361

IMMULITE® 2000 Syphilis Screen Device Name:

Indications for Use:

The IMMULITE® 2000 Syphilis Screen test is a treponemal testing procedure for the qualitative detection of antibodies to Treponema pallidum in human serum or heparinized plasma on the IMMULITE 2000 analyzer as an aid in the diagnosis of syphilis.

The IMMULITE 2000® Syphilis Screen is not intended for use in screening blood or plasma donors.

Prescription Use ✔ (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K091361

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