K Number
K062473
Manufacturer
Date Cleared
2007-04-12

(231 days)

Product Code
Regulation Number
866.3830
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The LIAISON® Borrelia burgdorferi assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative presumptive detection of IgG and IgM antibodies to VIsE (variable major protein-like sequence, expressed) protein antigen of Borrelia burgdorferi in human serum. This assay should be used only on samples from patients with signs and symptoms that are consistent with Lyme disease. Positive or equivocal results should be supplemented by testing with a standardized Western blot procedure. Positive supplemental results provide evidence of exposure to Borrelia burgdorferi and can be used to support a clinical diagnosis of Lyme disease. Negative results by LIAISON® Borrelia burgdorferi should not be used to exclude Lyme disease.

The LIAISON® Borrelia burgdorferi Serum Controls contains two assayed quality control sera (negative and positive) that are used to monitor the performance of the LIAISON® Borrelia burgdorferi assay.

Device Description

The method for the qualitative determination of IgG and IgM antibodies to Borrelia burgdorferi is an indirect chemiluminescence immunoassay (CLIA). All assay steps and incubations are performed by the LIAISON® Analyzer, with the exception of the initial magnetic particle resuspension. Recombinant antigens specific for Borrelia (VIsE antigens) are used for coating the magnetic particles (solid phase). Two mouse monoclonal antibodies (anti-human IgG and anti-human IqM) are linked to an isoluminol derivative (isoluminol-antibody coniugate). During the first incubation, anti-Borrelia burgdorferi antibodies present in calibrators, samples or controls bind to the solid phase magnetic particles. Unbound material is removed by a wash cycle and isoluminol-antibody conjugates are added. During the second incubation, the antibody conjugates react with anti-Borrelia burgdorferi IgG and IgM antibodies that are already bound to the solid phase. The second incubation is followed by a wash cycle to remove unbound conjugate. Subsequently, the start reagents are added and a flash chemiluminescence reaction is thus induced. The light signal and hence the amount of isoluminol-antibody coniuqate is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of Borrelia burgdorferi antibodies present in calibrators, controls or samples.

AI/ML Overview

Here's a detailed breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

Device Name: DiaSorin LIAISON® Borrelia burgdorferi and DiaSorin LIAISON® Borrelia burgdorferi Serum Controls

Intended Use: Qualitative presumptive detection of IgG and IgM antibodies to Borrelia burgdorferi in human serum, to be used only on samples from patients with signs and symptoms consistent with Lyme Disease. Positive/equivocal results need supplemental Western Blot testing.


1. Table of Acceptance Criteria and Reported Device Performance:

The document implicitly uses performance metrics like Percent Agreement (Sensitivity and Specificity related) and Reproducibility (%CV) as indicators of acceptable performance. Explicit acceptance criteria in terms of specific thresholds for these metrics are not stated in the provided text as 'acceptance criteria'. Instead, the study results are presented as evidence of adequate performance for substantial equivalence.

Performance MetricAcceptance Criteria (Implicit from context)Reported Device Performance
Comparative Clinical Trials
Lyme Disease Testing PatientsHigh agreement with comparator and Western Blot for positive/negative samplesPositive Agreement: 70.0% (35/50) (95% CI: 57.6 - 80.5%)Negative Agreement: 99.1% (973/982) (95% CI: 98.4 - 99.5%)Overall Agreement: 97.1% (1008/1038) (95% CI: 96.1 - 97.9%)(Vs. Comparator Immunetics® C6 ELISA™ Kit)
LIAISON vs. Western Blot (Positive/Equivocal Samples)Proportion of W. Blot positive results for LIAISON positive/equivocal samplesLIAISON Positive: 41 samples, 22 W. Blot positiveLIAISON Equivocal: 4 samples, 0 W. Blot positive
Apparently Healthy Adult Blood DonorsLow prevalence in healthy populationsEndemic Area: 0.7% Positive Prevalence (2/300)Non-Endemic Area: 0.3% Positive Prevalence (1/300)
Characterized Lyme Disease Samples (CDC)High agreement with characterized CDC samplesPositive Agreement: 93.2% (41/44) (95% CI: 83.3 – 98.1%)Negative Agreement: 81.3% (13/16) (95% CI: 58.3 – 94.5%)Overall Agreement: 90.0% (54/60) (95% CI: 83.3 – 95.5%)
LYMErix™ Vaccine RecipientsNo false positives for pre-vaccine negative samples; agreement for post-vaccinePre-vaccine Negative: 3/3 (100%) (95% CI: 36.9 - 100%)Post-vaccine Negative: 11/11 (100%) (95% CI: 76.1 - 100%)(Compared to Immunetics® C6 Lyme ELISA™ for pre/post vaccine status)
CDC Lyme serum panel (Time from Onset)Reasonable agreement across different stages of disease onsetNormals: 100% agreement (5/5)0-1 Month: 83.3% agreement (5/6)1-2 Months: 75.0% agreement (6/8)3-12 Months: 53.3% agreement (8/15)> 1 year: 100% agreement (8/8)Total: 73.0% agreement (27/42)
Reproducibility (Index & RLU)Low variability (%CV) across runs, days, sites, and instrumentsOverall %CV for Index: Ranges from 8.66% to 17.57% across different samples and sites.Overall %CV for RLU: Ranges from 9.58% to 14.31% across different samples and sites.Internal Reproducibility (Index): Overall %CV ranges from 8.06% to 14.20% across different samples.

2. Sample Size Used for the Test Set and Data Provenance:

  • Lyme Disease Testing Patients:
    • Sample Size: 1038
    • Data Provenance: Prospective samples tested at two external US laboratories and DiaSorin, Inc.
  • Apparently Healthy Adult Blood Donors:
    • Sample Size: 600 (300 from endemic areas, 300 from non-endemic areas)
    • Data Provenance: Prospective samples.
  • Characterized Lyme Disease Samples:
    • Sample Size: 60
    • Data Provenance: Retrospective samples provided by the Centers for Disease Control and Prevention (CDC), implying US origin.
  • LYMErix™ Vaccine Recipients:
    • Sample Size: 11
    • Data Provenance: Retrospective samples.
  • CDC Lyme Serum Panel:
    • Sample Size: 42
    • Data Provenance: Samples from the CDC, implying US origin.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

The document does not explicitly state the number or qualifications of experts used to establish a "ground truth" for the test set in the traditional sense of consensus reading for medical imaging. The ground truth for the clinical samples appears to be established through:

  • Comparator Assay: Immunetics® C6 B. burgdorferi (Lyme) ELISA™ Kit (K003754)
  • Standardized Western Blot Procedure: MarDx Marblot Western Blot IgG and IgM assay for confirming positive/equivocal results.
  • Clinical Diagnosis: For the CDC Lyme serum panel, samples had a "clinical diagnosis of Lyme Disease" and were categorized as "Normals (no Lyme Disease)". This implies a ground truth based on clinical assessment and established panels, rather than expert adjudication of individual cases.
  • CDC Characterized Samples: The "Characterized Lyme Disease Samples" from the CDC likely have their status (positive/negative) established by the CDC through a comprehensive approach including clinical, laboratory, and epidemiological data.

Therefore, there isn't a stated number of human "experts" directly establishing ground truth via case-by-case review as would be seen in AI studies for classification tasks.


4. Adjudication Method for the Test Set:

No explicit adjudication method (like 2+1, 3+1) is described for the test set. The ground truth relies on:

  • Comparison with a legally marketed predicate device (Immunetics® C6 B. burgdorferi (Lyme) ELISA™ Kit).
  • Confirmation of positive/equivocal results by a standardized Western Blot procedure.
  • Use of characterized panels from the CDC.
  • "Clinical diagnosis of Lyme Disease" for some samples in the CDC panel.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance:

No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay, not an AI software intended to assist human readers (e.g., radiologists). The study evaluates the performance of the assay itself compared to other diagnostic methods, not human performance with and without AI.


6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

Yes, the studies presented are standalone performance evaluations of the LIAISON® Borrelia burgdorferi assay. The "device" in this context is the automated chemiluminescent immunoassay (CLIA) system, which produces a result (qualitative presumptive detection of antibodies) without direct real-time human interpretation or assistance during the assay process. The results are then read and potentially followed up by a clinician, but the assay itself functions independently.


7. The Type of Ground Truth Used:

The ground truth used in the studies is a combination of:

  • Comparator Assay Results: The Immunetics® C6 B. burgdorferi (Lyme) ELISA™ Kit was used as a comparator.
  • Standardized Western Blot Results: Used as a confirmatory test for positive/equivocal results.
  • Characterized Samples/Panels: Samples provided by the CDC which are stated as "Characterized Lyme Disease Samples" or have a "clinical diagnosis of Lyme Disease," indicating a ground truth established by a combination of clinical, laboratory, and epidemiological data.

8. The Sample Size for the Training Set:

The document does not provide information on a training set sample size or how the device was "trained." This is because the device is an immunoassay kit and an analyzer, not a machine learning or AI algorithm in the contemporary sense that would require a distinct training set for algorithm development. The "training" of such a device primarily involves assay development, optimization, and validation procedures, not iterative learning from a labeled dataset.


9. How the Ground Truth for the Training Set Was Established:

As explained in point 8, there is no explicit "training set" in the context of an AI/ML algorithm. Therefore, information on how a ground truth for a training set was established is not applicable and not provided in the document. The device's performance is driven by its biochemical reagents and optical detection system, which are developed and optimized through traditional laboratory methods rather than machine learning on a labeled dataset.

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K062473

510(k) SUMMARY 5.0

APR 1 2 2007

SUBMITTED BY:Carol A. DePouwRegulatory Affairs SpecialistDiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285Phone (651) 351-5850Fax (651) 351-5669Email: carol.depouw@diasorin.com
NAME OF DEVICE:
Trade Name:DiaSorin LIAISON® Borrelia burgdorferiDiaSorin LIAISON® Borrelia burgdorferiSerum Controls
Common Names/Descriptions:Borrelia burgdorferi IgG/IgM
Classification Names:Reagent, Borrelia Serological Reagent
Product Code:LSR
PREDICATE DEVICES:Immunetics® C6 B. burgdorferi (Lyme)ELISA ™ Kit - (K003754)

DEVICE DESCRIPTION:

INTENDED USE: The LIAISON® Borrelia burgdorferi assay and the LIAISON® Borrelia burgdorferi Serum Controls, use chemiluminescent immunoassay (CLIA) technology for the qualitative presumptive detection of IgG and IgM antibodies to Borrelia burgdorferi in human serum. This assay should be used only on samples from patients with signs and symptoms that are consistent with Lyme Disease. Positive or equivocal results should be supplemented by testing with a standardized Western Blot procedure. Positive supplemental results provide evidence of exposure to Borrelia burgdorferi and can be used to support a clinical diagnosis of Lyme Disease. Negative results by LIAISON® Borrelia burgdorferi assay should not be used to exclude Lyme Disease.

KIT DESCRIPTION: The method for the qualitative determination of IgG and IgM antibodies to Borrelia burgdorferi is an indirect chemiluminescence immunoassay (CLIA). All assay steps and incubations are performed by the LIAISON® Analyzer, with the exception of the initial magnetic particle resuspension.

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Recombinant antigens specific for Borrelia (VIsE antigens) are used for coating the magnetic particles (solid phase). Two mouse monoclonal antibodies (anti-human IgG and anti-human IqM) are linked to an isoluminol derivative (isoluminol-antibody coniugate).

During the first incubation, anti-Borrelia burgdorferi antibodies present in calibrators, samples or controls bind to the solid phase magnetic particles. Unbound material is removed by a wash cycle and isoluminol-antibody conjugates are added. During the second incubation, the antibody conjugates react with anti-Borrelia burgdorferi IgG and IgM antibodies that are already bound to the solid phase. The second incubation is followed by a wash cycle to remove unbound conjugate. Subsequently, the start reagents are added and a flash chemiluminescence reaction is thus induced. The light signal and hence the amount of isoluminol-antibody coniuqate is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of Borrelia burgdorferi antibodies present in calibrators, controls or samples.

PERFORMANCE DATA:

Performance testing of the LIAISON® Borrelia burgdorferi Assay for comparative clinical trials consisted of running selected samples to support the intended use.

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 were tested by LIAISON® Borrella burgdorferi and the comparator assay Immunetics® C6 B. burgdorferi (Lyme) ELISA ™ kit at the trial sites per the manufacturer's instructions for use. The study consisted of the following samples types and results.

Lyme Disease Testing Patients: Prospective samples (n=1038).

Percent Agreement95% Confidence Interval
Positive70.0% (35/50)57.6 - 80.5%
Negative99.1% (973/982)98.4 - 99.5%
Overall97.1% (1008/1038)96.1 - 97.9%

Forty-five samples were positive or equivocal by LIAISON® Borrelia burgdorferi in the 1038 prospective sample study. These 45 samples were then tested following the two step method with a standardized Western Blot assay (MarDx Marblot Western Blot IgG and IgM assay). Twenty-two of the 45 total samples were W. Blot positive. Of the 22 samples that were Western Blot positive, 6 were IgM +, 12 were lgG +, and 4 were both IgM and IgG +.

Fifty-six samples were positive or equivocal by the Immunetics® C6 B. buradorferi (Lyme) ELISA™. These 56 samples were also tested following the two step method. Twenty-three of the 56 total samples were W. Blot positive. Of the 23

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samples that were Western Blot positive 6 were IgM +, 13 were IgG +, and 4 were both IgM and IgG +. A summary of the results are in the following table.

AssayResultnCombined IgG and IgM W. Blot results
+-
LIAISON+412219
LIAISON±404
C6ELISA+502327
C6ELISA±606

Apparently Healthy Adult Blood Donors: Prospective samples from areas where Lyme disease is Endemic (n= 300) and Non-Endemic (n = 300). Reactivity/Prevalence in the Normal population was determined from these samples types.

PopulationNNegativeEquivocalPositive% Positive Prevalence
Endemic300297120.7%
Non-Endemic300299010.3%
  • Characterized Lyme Disease Samples. Retrospective samples provided by the Centers for Disease Control and Prevention (n=60).

Percent Agreement95% Confidence Intervals
Positive93.2%(41/44)83.3 – 98.1%
Negative81.3%(13/16)58.3 – 94.5%
Overall90.0%(54/60)83.3 – 95.5%
  • LYMErix™ Vaccine Recipients: Retrospective samples (n=11). (LYMErix® manufactured by GlaxoSmithKline Biologicals)

Immunetics® C6 Lyme ELISA
Pre vaccine NegativePost vaccine Negative
LIAISON®Borrelia burgdorferiAssay3 /3 (100%)95% CI = 36.9 - 100%11/ 11 (100%)95% CI = 76.1 - 100%
  • A CDC Lyme serum panel: (n = 42) The samples are categorized as Normals (no Lyme Disease n=5). The remaining 37 samples have a clinical diagnosis of Lyme Disease and are presented as Time from Onset of disease.

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LIAISON® Borrelia burgdorferi
Time afterOnsetTotalPosEqvNeg%Agreement
Normals5005100%
0-1 Month650183.3%
1-2 Months860275.0%
3-12 Months1580753.3%
> 1 year8800100%
Total422701573.0%

Conclusion:

The results demonstrate that the LIAISON® Borrelia burgdorferi assay can be used with the LIAISON® Analyzer for the qualitative presumptive detection of IgG and IgM antibodies to Borrelia burgdorferi in human serum.

REPRODUCIBILITY: Reproducibility studies were performed at 3 sites using a coded panel comprised of 6 prepared serum samples. The same coded panel was tested at all 3 sites following CLSI EP15-A2. Panel samples were tested in four replicates per run, in one run per day, during five operating days.

The results expressed for Index and RLU's are summarized in the tables below.

sampleNmeanIndexWithinrun%CVbetweenrun%CVtotal(by site)%CVbetweensite%CVoverall%CV
ID#matrix
NCSerum600.066.778.2610.9315.6417.28
PCSerum601.955.075.927.375.148.68
BPP1Serum600.905.389.4910.6811.7014.42
BPP2Serum601.013.949.079.246.1911.31
BPP3Serum606.83.966.347.682.018.66
BPP4Serum601.843.457.858.064.2110.19
BPP5Serum600.446.1012.1912.6613.7617.57
BPP6Serum600.135.8810.6611.678.0413.81

Index Reproducibility

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samplewithinbetweentotalbetweenoverall
ID#matrixNmeanRLUrun%CVrun%CV(by site)%CVsite%CV%CV
NCSerum6015165.766.108.175.789.74
PCSerum60442933.964.585.808.859.58
BPP1Serum60212434.907.378.858.1211.79
BPP2Serum60237203.527.788.034.6310.24
BPP3Serum601437573.886.067.415.639.77
BPP4Serum60420163.276.797.216.3410.73
BPP5Serum60107695.7310.2311.017.6114.31
BPP6Serum6033205.828.089.646.5712.58

RLU Reproducibility

Studies were tested internally at DiaSorin Inc. using the same coded panel following CLSI EP5-A2. Samples were tested in 2 replicates per run, on 2 different instruments 2 times per day for 20 days. The results are in the following table.

IDNMeanIndexwithinrunSDwithinrun%CVbetweenrunSDbetweenrun%CVbetweeninstrumentSDbetweeninstrument%CVoverallSDoverall%CV
NegQC-A1600.070.004.120.018.020.001.910.019.24
PosQC-A1602.110.073.420.178.080.052.420.198.85
BPP11601.110.033.120.087.640.021.630.098.22
BPP21601.360.086.100.129.180.010.710.1914.03
BPP31607.60.364.650.506.590.162.140.709.12
BPP41602.220.073.180.177.480.052.110.188.06
BPP51600.620.023.670.058.810.023.160.069.49
BPP61600.180.015.590.018.240.000.350.0314.20

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.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The logo is black and white.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

APR 1 2 2007

K062473 Re:

Trade/Device Name: LIAISON® Borrelia burgdorferi LIAISON® Borrelia burgdorferi Serum Controls Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema pallidum treponemal test reagents Regulatory Class: Class II Product Code: LSR Dated: February 2, 2007 Received: February 5, 2007

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 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 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 Register.

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).

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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 (240)276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained 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/dsma/dsmamain.html.

Sincerely yours.

Sally, axtym

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

LIAISON® Borrelia burgdorferi

510(k) Number (if known): K062473

Device Name:

Indications For Use:

The LIAISON® Borrelia burgdorferi assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative presumptive detection of IgG and IgM antibodies to VIsE (variable major protein-like sequence, expressed) protein antigen of Borrelia burgdorferi in human serum. This assay should be used only on samples from patients with signs and symptoms that are consistent with Lyme disease. Positive or equivocal results should be supplemented by testing with a standardized Western blot procedure. Positive supplemental results provide evidence of exposure to Borrelia burgdorferi and can be used to support a clinical diagnosis of Lyme disease. Negative results by LIAISON® Borrelia burgdorferi should not be used to exclude Lyme disease.

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 IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Jayart
Division Sign-Off

Page 1 of 1

Office of In Vita Diagnostic Device Eveluction and Safety

51000

Section 4

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Indications for Use

510(k) Number (if known): K062473

Device Name:

LIAISON® Borrelia burgdorferi Serum Controls

Indications For Use:

The LIAISON® Borrelia burgdorferi Serum Controls contains two assayed quality control sera (negative and positive) that are used to monitor the performance of the LIAISON® Borrelia burgdorferi assay.

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 IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Jauzaix
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of 1

Section 4

Page 4-3

§ 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).