(222 days)
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.
The IMMULITE 2000 Syphilis Screen is a solid-phase, one-step chemiluminescent immunoassay. The solid phase (bead) is coated with biotinylated recombinant Treponema pallidum p17 (Tp17) antigen. The liquid phase consists of alkaline phosphatase (bovine calf intestine) conjugated to purified recombinant Treponema pallidum p17 (Tp17) antigen.
The patient sample and reagent are incubated together with the coated bead for 30 minutes. During this time, total antibody to Treponema pallidum in the sample forms an antigen sandwich complex with biotinylated recombinant Treponema pallidum pl 7 (Tp17) antigen on the bead and enzyme conjugated purified recombinant Treponema pallidum p17 (Tp17) antigen in the reagent. Unbound patient sample and enzyme conjugate are then removed by centrifugal washes. Finally, chemiluminescent substrate is added to the reaction tube containing the bead and the signal is generated in proportion to the bound enzyme.
Here's a breakdown of the acceptance criteria and study information for the IMMULITE® 2000 Syphilis Screen device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" as a separate section with predefined thresholds. Instead, it presents a method comparison study between the IMMULITE® 2000 Syphilis Screen and the predicate device (DiaSorin LIASION® Treponema Assay). The performance of the new device is demonstrated through its agreement with the predicate.
For the purpose of this request, the "acceptance criteria" are inferred from the good performance values observed in the method comparison study, particularly the high positive and negative agreement rates.
| Performance Metric | Acceptance Criteria (Implicit from Predicate Performance/Study Results) | Reported Device Performance (IMMULITE 2000 Syphilis Screen) |
|---|---|---|
| Method Comparison (Medically Diagnosed Syphilis Patients) | ||
| Positive Agreement (vs. LIAISON Treponema Assay) | High agreement (e.g., > 95%) | 99.3% (270/272) (95% CI: 97.4% - 99.9%) |
| Negative Agreement (vs. LIAISON Treponema Assay) | Sufficient agreement to demonstrate comparable performance (not explicitly stated a threshold, but >75% is shown here) | 75% (6/8) (95% CI: 34.9% - 96.8%) |
| Overall Agreement (vs. LIAISON Treponema Assay) | High overall agreement (e.g., > 95%) | 98.2% (276/281) (95% CI: 95.9% - 99.4%) |
| Method Comparison (Samples for Routine Syphilis Testing) | ||
| Positive Agreement (vs. LIAISON Treponema Assay) | High agreement (e.g., > 95%) | 99.4% (359/361) (95% CI: 98.0% - 99.9%) |
| Negative Agreement (vs. LIAISON Treponema Assay) | High agreement (e.g., > 95%) | 99.1% (558/563) (95% CI: 97.9% - 99.7%) |
| Overall Agreement (vs. LIAISON Treponema Assay) | High overall agreement (e.g., > 95%) | 99.2% (917/924) (95% CI: 98.4% - 99.7%) |
| Reproducibility (Between-site Coefficient of Variation - CV) | Comparable to predicate device (LIAISON Treponema Assay: 4.32% to 17.76%) | Lot 1: 7.1% to 22.6%Lot 2: 6.1% to 29.7% (for the same 7 samples tested with both IMMULITE lots) |
2. Sample Sizes Used for the Test Set and Data Provenance:
- Medically Diagnosed Syphilis Patients: 281 samples
- Samples Sent for Routine Syphilis Testing: 924 samples
- Data Provenance: The document does not explicitly state the country of origin. It mentions "samples from various patient populations were tested," which suggests diverse sources, but no specifics are given. The study appears to be retrospective as it involves "samples from various patient populations were tested with both the IMMULITE Syphilis Screen and the LIAISON Treponema Assay," implying pre-collected samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
The document does not mention the use of experts to establish ground truth for the test set. The "ground truth" for comparison is the DiaSorin LIASION® Treponema Assay. For the "Medically Diagnosed Syphilis Patients" cohort, their diagnosis would likely have involved clinical assessments and other laboratory tests by healthcare professionals, but no specific number or qualifications of experts are provided for the study's ground truth determination.
4. Adjudication Method for the Test Set:
No adjudication method is described. The comparison is directly between the IMMULITE 2000 Syphilis Screen and the LIAISON Treponema Assay, which serves as the reference (ground truth for agreement calculations).
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done:
No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) immunoassay, not an imaging or diagnostic device requiring human interpretation of results in the traditional sense of an MRMC study. Its performance is evaluated quantitatively or qualitatively against a reference method.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done:
Yes, a standalone performance evaluation of the IMMULITE® 2000 Syphilis Screen was performed. The device, an automated immunoassay, generates results without human intervention in the interpretation of the test itself. The study compared these standalone results directly against those of the predicate device (LIAISON Treponema Assay).
7. The Type of Ground Truth Used:
The primary "ground truth" for determining performance was the DiaSorin LIASION® Treponema Assay.
Additionally, for the "Medically Diagnosed Syphilis Patients" group, the "ground truth" was established by medical diagnosis, likely an aggregation of clinical findings and other laboratory results, preceding the testing with the LIAISON assay. The document states "Medically Diagnosed Syphilis Patients", implying an established patient status.
8. The Sample Size for the Training Set:
The document does not provide information on a training set sample size. As a diagnostic immunoassay, the development process typically involves internal optimization and validation, but specific "training set" and "test set" terminology in the context of machine learning algorithms (which this device is not) is not directly applicable or reported here. The clinical study described focuses on the device's performance against a predicate and existing patient cohorts.
9. How the Ground Truth for the Training Set Was Established:
Since a training set is not explicitly mentioned or relevant in the context of the reported study for this immunoassay device, the method for establishing its ground truth is not provided. Device development would involve rigorous analytical validation, but this is distinct from the type of ground truth establishment relevant to AI/ML model training.
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DEC 1 6 2009
| 510(k) Summary as Required by 21 CFR 807.92 | |||
|---|---|---|---|
| Submitter: | Siemens Healthcare Diagnostics Inc.5210 Pacific Concourse DriveLos Angeles, CA 90045-6900 | ||
| Contact Person: | Robert C. EusebioDirector Regulatory Affairs1584 Enterprise BlvdWest Sacramento, CA 95691(916) 374-3183 | ||
| Date Prepared: | September 10, 2009 | ||
| Device Trade Name: | IMMULITE® 2000 Syphilis Screen | ||
| Common Name: | Immunoassay for Treponema pallidum21 CFR 866.3830 | ||
| Substantial Equivalence: | K061247DiaSorin LIASION® Treponema Assay | ||
| Device Description: | The IMMULITE 2000 Syphilis Screen is a solid-phase, one-step chemiluminescent immunoassay. The solid phase (bead) iscoated with biotinylated recombinant Treponema pallidum p17(Tp17) antigen. The liquid phase consists of alkalinephosphatase (bovine calf intestine) conjugated to purifiedrecombinant Treponema pallidum p17 (Tp17) antigen. | ||
| The patient sample and reagent are incubated together with thecoated bead for 30 minutes. During this time, total antibody toTreponema pallidum in the sample forms an antigen sandwichcomplex with biotinylated recombinant Treponema pallidumpl 7 (Tp17) antigen on the bead and enzyme conjugated purifiedrecombinant Treponema pallidum p17 (Tp17) antigen in thereagent. Unbound patient sample and enzyme conjugate arethen removed by centrifugal washes. Finally,chemiluminescent substrate is added to the reaction tubecontaining the bead and the signal is generated in proportion tothe bound enzyme. |
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| Intended Use: | The IMMULITE® 2000 Syphilis Screen test is atreponemal testing procedure for the qualitativedetection of antibodies to Treponema pallidum in humanserum or heparinized plasma on the IMMULITE 2000analyzer as an aid in the diagnosis of syphilis.The IMMULITE 2000 Syphilis Screen is not intendedfor use in screening blood or plasma donors. |
|---|---|
| Technological Aspects: | A comparison of the device features, intended use, laboratorydata and other information demonstrate that the IMMULITE®2000 Syphilis Screen is substantially equivalent to thecurrently marketed DiaSorin LIASION® Treponema Assay,as summarized in the following tables. |
| Table 1: Comparison of IMMULITE® with LIAISON® Assay | |
|---|---|
| IMMULITE 2000 | LIAISON | |
|---|---|---|
| Indications for Use | The IMMULITE® 2000 SyphilisScreen test is a treponemal testingprocedure for the qualitativedetection of antibodies to Treponemapallidum in human serum orheparinized plasma on theIMMULITE 2000 analyzer as an aidin the diagnosis of syphilis.The IMMULITE 2000 SyphilisScreen is not intended for use inscreening blood or plasma donors. | The LIAISON Treponema assay useschemiluminescence immunoassay(CLIA) technology for the qualitativedetection of total antibodies directedagainst Treponema pallidum inhuman serum. The presence ofantibodies to Treponema pallidumspecific antigen, in conjunction withnon-treponemal laboratory tests andclinical findings, may aid in thediagnosis of syphilis infection.The LIAISON Treponema Assay isnot intended for use in screeningblood or plasma donors. |
| Assay Type | Enzyme labeled, one-stepchemiluminescent immunoassay | One-step sandwich chemiluminescentimmunoassay |
| Capture/DetectionAntigen/Antibody | Beads coated with purifiedrecombinant Treponema pallidum p17(TpN17) antigens are linked toenzyme conjugated purifiedrecombinant Treponema pallidum p17antigen in the reagent. | Magnetic particles coated with Tp17DNA recombinant protein specific forTreponema pallidum are linked to anisoluminol derivative (isoluminol-antigen conjugate). |
| Cut-Offs | Test value = ratio of signal fromsample to that of signal of adjustorcurve parameter P1. | Index value = ratio of signal fromsample to that of the standard |
| $\geq$ 1.1 Reactive0.9 to $<$ 1.1 Indeterminate$<$ 0.9 Non-reactive | $\geq$ 1.1 Positive0.9 to $<$ 1.1 Equivocal$<$ 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 orlipemia at test levels | Not affected by hemolysis, icterus orlipemia 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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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's emblem, which is a stylized representation of a human figure embracing a sphere. The emblem is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA", which is arranged in a circular fashion around the emblem.
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 (301) 796-5455. 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 (800) 638-2041 or (301) 443-6597 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
Page 1 of
§ 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).