(167 days)
The LIAISON® Lyme IgG assay uses chemiluminescent immunoassay (CLIA) technology for the qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum and plasma specimens (K2-EDTA, Li-heparin). This assay is intended for use on samples from patients with signs and symptoms consistent with or patients suspected of having Lyme disease to assess the presence of IgG antibodies and exposure to Borrelia burgdorferi. In addition, the LIAISON® Lyme Ig G assay may be used as a confirmatory test in the modified two-tier test (MTTT) in combination with the DiaSorin LIAISON® Lyme Total Antibody Plus assay.
If used as a first stage test, positive or equivocal results with the LIAISON® Lyme IgG assay should be confirmed through additional testing with a Standard two-tier test (STT) methodology using an IgG Borrelia burgdorferi Western blot test following current guidelines.
Positive supplemental results are supportive evidence of the presence of antibodies and exposure to Borrelia burgdorferi and may be used along with patient history, symptoms and other laboratory data to support a clinical diagnosis of Lyme disease.
Negative results by the LIAISON® Lyme IgG assay should not be used to exclude Lyme disease.
The test must be performed on the LIAISON® XL Analyzer.
The DiaSorin LIAISON® Lyme IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Lyme IgG assay. The performance characteristics of LIAISON® Lyme IgG controls have not been established for any other assays or instrument platforms different from the LIAISON® XL.
The LIAISON® Lyme IgG assay is an indirect chemilyminescence immunoassay (CLIA) for the qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum and plasma samples. All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the Analyzer. The principal components of the test are magnetic particles (solid phase) coated with recombinant Borrelia antigens and a conjugate reagent containing an anti-human IgG mouse monoclonal antibody 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. Unbound material is then removed with a wash cycle. During the second incubation, the antibody conjugate reacts with anti-Borrelia burgdorferi IgG antibodies that have bound to the solid phase. Excess antibody conjugate is then 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-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of Borrelia burgdorferi IgG antibodies present in calibrators, samples or controls.
Here's a breakdown of the acceptance criteria and study details for the LIAISON® Lyme IgG assay, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance:
The document implicitly defines acceptance criteria through its performance study results, specifically for percentage agreement (sensitivity and specificity) when compared to a predicate device and STTT/MTTT protocols.
Acceptance Criteria (Implicitly defined by performance targets in studies)
| Performance Metric | Acceptance Criteria (from study context) | Reported Device Performance (LIAISON® Lyme IgG) | Study Context |
|---|---|---|---|
| First Tier Agreement with Predicate Device (ZEUS ELISA B. burgdorferi IgG Test System) | |||
| Positive % Agreement | Implied high agreement (no specific % mentioned but demonstrated acceptability) | 55.1% (166/301) | Comparison to Predicate ELISA IgG |
| Negative % Agreement | Implied high agreement (no specific % mentioned but demonstrated acceptability) | 96.5% (2210/2320) | Comparison to Predicate ELISA IgG |
| Standard Two-Tier Testing Methodology (STTT - WB IgG) | |||
| 2nd Tier PPA (Positive Percent Agreement) | Implied high PPA | 89.0% (97/109) | Comparison to STTT WB IgG |
| 2nd Tier NPA (Negative Percent Agreement) | Implied high NPA | 99.5% (2500/2512) | Comparison to STTT WB IgG |
| Modified Two-Tier Testing Methodology (MTTT - Prospective Population - STTT WB IgG as GT) | |||
| PPA (Positive Percent Agreement) | Implied high PPA | 96.9% (93/96) | Comparison to STTT WB IgG |
| NPA (Negative Percent Agreement) | Implied high NPA | 30.2% (39/129) | Comparison to STTT WB IgG |
| Modified Two-Tier Testing Methodology (MTTT - Retrospective CDC Panel - STTT WB IgG as GT) | |||
| Sensitivity (Stage I) | Implied high Sensitivity | 80% | Comparison to STTT WB IgG |
| Sensitivity (Stage II) | Implied high Sensitivity | 90% | Comparison to STTT WB IgG |
| Sensitivity (Stage III) | Implied high Sensitivity | 100% | Comparison to STTT WB IgG |
| Specificity (Healthy Controls) | Implied high Specificity | 100% | Comparison to STTT WB IgG |
| Specificity (Disease Controls) | Implied high Specificity | 97.8% | Comparison to STTT WB IgG |
Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria for each metric (e.g., "PPA must be >X%"). Instead, it presents the device's performance results and concludes substantial equivalence, implying that these results met the FDA's expectations for equivalence to legally marketed predicate devices.
2. Sample Size Used for the Test Set and Data Provenance:
- Method Comparison (First Tier and STTT):
- Sample Size: 2621 human serum specimens.
- Data Provenance: Collected in 14 states across five (5) distinct U.S. geographical regions. This was a prospective study ("All 2621 prospective (all comer) specimens").
- Modified Two Tier Testing Methodology (Prospective Population):
- Sample Size: 225 specimens (from the initial 2621 that were positive or equivocal by the first-tier assay).
- Data Provenance: U.S. geographical regions, prospective.
- Characterized Lyme Panel (CDC Panel):
- Sample Size: 280 samples.
- Data Provenance: Acquired from the CDC (Centers for Disease Control), making it a retrospective panel.
- Modified Two Tier Testing Methodology (Retrospective Population from CDC Panel):
- Sample Size: 279 samples (1 sample from the 280 CDC panel lacked sufficient volume). 82 of these were further tested with STTT WB IgG or MTTT.
- Data Provenance: CDC, retrospective.
- Cross-reactivity Study:
- Sample Size: 222 specimens (from 22 different disease states).
- Data Provenance: Not specified, but likely obtained from various sources or commercial vendors for specific disease states. Retrospective by nature of obtaining specific disease samples.
- Matrix Equivalence Study:
- Sample Size: 32 matched patient sets.
- Data Provenance: Not specified.
3. Number of Experts Used to Establish Ground Truth and Qualifications:
The document does not explicitly state the "number of experts" or their specific "qualifications" for establishing ground truth. However, the ground truth for some studies is based on established laboratory methods:
- For the Method Comparison and STTT/MTTT studies: The ground truth for confirming Borrelia burgdorferi infection or exposure is primarily established by Western blot testing (IgG Borrelia burgdorferi Western blot test) following current guidelines. This is a recognized laboratory "gold standard" or highly accepted confirmatory method for Lyme disease. While experts interpret WBs, the document doesn't detail the number or qualifications of individuals performing or interpreting these specific Western blots.
- For the Characterized Lyme Panel (CDC Panel): The samples were "characterized" by the CDC. This implies that the CDC itself, a leading public health agency with extensive expertise in infectious diseases, established the reference classification for these samples. The ground truth here is the CDC's reference classification, which would involve robust testing and expert consensus within the CDC, though specific expert numbers or qualifications are not provided in this submission summary.
4. Adjudication Method for the Test Set:
Not explicitly described in the document. The studies primarily compare the LIAISON® Lyme IgG assay results against either a predicate ELISA assay or Western Blot results (STTT/MTTT). There isn't mention of a separate adjudication process beyond the defined "ground truth" method (e.g., WB results).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study, as typically understood for AI-assisted image analysis where human readers improve with AI vs without AI assistance, was not explicitly mentioned or performed. This device is an in-vitro diagnostic (IVD) assay designed to detect antibodies, not an AI-powered diagnostic imaging system requiring human interpretation with AI assistance. Its performance is measured directly against other laboratory tests or characterized panels.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the performance studies described are essentially standalone evaluations of the LIAISON® Lyme IgG assay. The assay is an automated chemiluminescent immunoassay (CLIA) performed on the LIAISON® XL Analyzer. The results (Index values) lead to a qualitative positive, negative, or equivocal determination by the instrument's algorithm based on a predefined cutoff. There is no human-in-the-loop performance described in the context of interpreting the assay's primary output. Human involvement is in running the test and interpreting the final qualitative result provided by the system within a clinical context.
7. The Type of Ground Truth Used:
- Expert Consensus / Established Gold Standard:
- For the prospective and retrospective studies that compare the LIAISON® assay to STTT (Standard Two-Tier Test) or MTTT (Modified Two-Tier Test), the ground truth is primarily based on IgG Borrelia burgdorferi Western Blot testing following current guidelines. Western blot is generally considered the confirmatory "gold standard" for Lyme disease serology.
- For the "Characterized Lyme Panel" (from CDC), the ground truth is the CDC Reference Classification, which would be based on comprehensive testing and expert knowledge.
- Predicate Device Comparison: In the initial method comparison, the ground truth for calculating agreement percentages is the ZEUS ELISA B. burgdorferi IgG Test System (predicate device).
8. The Sample Size for the Training Set:
The document describes performance studies (method comparison, STTT, MTTT, cross-reactivity, precision, reproducibility, etc.) of the LIAISON® Lyme IgG assay. It does not explicitly mention a "training set" or "validation set" in the context of an algorithm or AI model development. The reported studies represent the testing and validation of the already developed assay.
- However, for the assay development process itself (not detailed in this summary), a training phase would typically occur during the R&D of the assay to establish optimal reagent concentrations, cut-offs, and assay parameters. This information is generally proprietary to the manufacturer and not typically included in a 510(k) summary unless the device is a novel AI/ML product.
- The calibration described ("Two-point verification (in triplicate) of stored 10 point master curve") indicates a specific calibration approach for the instrument, which would have been established during initial assay development using a set of characterized samples. The number of samples for developing this master curve is not provided.
9. How the Ground Truth for the Training Set Was Established:
As noted above, a distinct "training set" for an AI/ML algorithm is not described here, as this is an immunoassay. For the development of the assay itself (e.g., establishing optimal cut-offs), the ground truth would have been established using well-characterized samples from known Lyme disease patients and healthy controls, likely confirmed by established methods like Western blot and/or clinical diagnosis, similar to the methods used to establish the ground truth for the test sets presented. The specifics of this internal R&D process are not detailed in the FDA summary.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol representing the Department of Health & Human Services. To the right of the symbol, there is the FDA logo in blue, followed by the words "U.S. FOOD & DRUG" in a larger font and "ADMINISTRATION" in a smaller font below it, also in blue.
February 18, 2021
DiaSorin Inc. Carol Depouw Principal Regulatory Affairs Specialist 1951 Northwestern Avenue Stillwater, Minnesota 55082
Re: K202574
Trade/Device Name: LIAISON Lyme IgG, LIAISON Lyme IgG Control Set, LIAISON Lyme Total Antibody Plus Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema Pallidum Treponemal Test Reagents Regulatory Class: Class II Product Code: LSR Dated: September 2, 2020 Received: September 4, 2020
Dear Carol 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Maria Ines Garcia, Ph.D. Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K202574
Device Name LIAISON® Lyme IgG assay: LIAISON® Lyme IgG Control Set
Indications for Use (Describe)
The LIAISON® Lyme IgG assay uses chemiluminescent immunoassay (CLIA) technology for the qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum and plasma specimens (K2-EDTA, Li-heparin). This assay is intended for use on samples from patients with signs and symptoms consistent with or patients suspected of having Lyme disease to assess the presence of IgG antibodies and exposure to Borrelia burgdorferi. In addition, the LIAISON® Lyme Ig G assay may be used as a confirmatory test in the modified two-tier test (MTTT) in combination with the DiaSorin LIAISON® Lyme Total Antibody Plus assay.
If used as a first stage test, positive or equivocal results with the LIAISON® Lyme IgG assay should be confirmed through additional testing with a Standard two-tier test (STT) methodology using an IgG Borrelia burgdorferi Western blot test following current guidelines.
Positive supplemental results are supportive evidence of the presence of antibodies and exposure to Borrelia burgdorferi and may be used along with patient history, symptoms and other laboratory data to support a clinical diagnosis of Lyme disease.
Negative results by the LIAISON® Lyme IgG assay should not be used to exclude Lyme disease.
The test must be performed on the LIAISON® XL Analyzer.
The DiaSorin LIAISON® Lyme IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Lyme IgG assay. The performance characteristics of LIAISON® Lyme IgG controls have not been established for any other assays or instrument platforms different from the LIAISON® XL.
| Type of Use (Select one or both, as applicable) | ||||
|---|---|---|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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5.0 510(k) SUMMARY
| SUBMITTED BY: | Carol A. DePouwDiaSorin Inc.1951 Northwestern AvenueStillwater, MN 55082-0285Phone (651) 439-9710Fax (651) 351-5669Email carol.depouw@diasorin.com |
|---|---|
| DATE PREPARED: | September 01, 2020 |
| NAME OF DEVICE:Trade Name: | LIAISON® Lyme IgGLIAISON® Lyme IgG Control Set |
| Common Names/Descriptions: | Borrelia burgdorferi IgG assay andBorrelia burgdorferi IgG controls |
| Classification Names: | Treponema pallidum; treponemal test reagentsClass II, 21 CFR: 866.3830; Microbiology |
| Product Code: | LSR and QCH |
| Predicate Device: | ZEUS ELISA B. burgdorferi IgG Test System(K895292)/modified (K191398) |
INTENDED USE:
The LIAISON® Lyme IgG assay uses chemiluminescent immunoassay (CLIA) technology for the qualitative detection of IqG antibodies to Borrelia burqdorferi in human serum and plasma specimens (K2-EDTA, Li-heparin). This assay is intended for use on samples from patients with signs and symptoms consistent with or patients suspected of having Lyme disease to assess the presence of IgG antibodies and exposure to Borrelia burgdorferi. In addition, the LIAISON® Lyme IgG assay may be used as a confirmatory test in the modified two-tier test (MTT) in combination with the DiaSorin LIAISON® Lyme Total Antibody Plus assay.
If used as a first stage test, positive or equivocal results with the LIAISON® Lyme IgG assay should be confirmed through additional testing with a Standard two-tier test (STTT) methodology using an IgG Borrelia burgdorferi Western blot assay following current quidelines.
Positive supplemental results are supportive evidence of the presence of antibodies and exposure to Borrelia burgdorferi and may be used along with patient history, symptoms and other laboratory data to support a clinical diagnosis of Lyme disease.
Negative results by the LIAISON® Lyme IgG assay should not be used to exclude Lyme disease.
The test must be performed on the LIAISON® XL Analyzer.
The LIAISON® Lyme IgG Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Lyme IgG assay. The performance characteristics of LIAISON® Lyme IgG controls have not been established for any other assays or instrument platforms different from the LIAISON® XL.
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KIT DESCRIPTION:
The LIAISON® Lyme IgG assay is an indirect chemilyminescence immunoassay (CLIA) for the qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum and plasma samples. All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the Analyzer. The principal components of the test are magnetic particles (solid phase) coated with recombinant Borrelia antigens and a conjugate reagent containing an anti-human IgG mouse monoclonal antibody 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. Unbound material is then removed with a wash cycle. During the second incubation, the antibody conjugate reacts with anti-Borrelia burgdorferi IgG antibodies that have bound to the solid phase. Excess antibody conjugate is then 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-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of Borrelia burgdorferi IgG antibodies present in calibrators, samples or controls.
| Table 1: Table of Similarities | |
|---|---|
| Characteristic | Candidate DeviceLIAISON® Lyme IgG |
| Intended Use | Qualitative detection of IgG antibodies to Borreliaburgdorferi in human serum and plasmaspecimens. This assay is intended for use onsamples from patients with signs and symptomsconsistent with or patients suspected of havingLyme disease to assess the presence of IgGantibodies and exposure to Borrelia burgdorferi.In addition, the LIAISON® Lyme IgG assay may beused as a confirmatory test in the modified two-tiertest (MTTT) in combination with the DiaSorinLIAISON® Lyme Total Antibody Plus assay.If used as a first stage test, positive or equivocalresults with the LIAISON® Lyme IgG assay shouldbe confirmed through additional testing with aStandard two-tier test (STTT) methodology usingan IgM Borrelia burgdorferi Western blot testfollowing current guidelines.Positive supplemental results are supportiveevidence of the presence of antibodies andexposure to Borrelia burgdorferi and may be usedalong with patient history, symptoms and otherlaboratory data to support a clinical diagnosis ofLyme disease.Negative results by the LIAISON® Lyme IgG assayshould not be used to exclude Lyme disease. |
| Predicate DeviceZEUS ELISABorrelia burgdorferi IgG Test System –K895292/K191398 | |
| Qualitative detection of IgG class antibody toBorrelia burgdorferi in human serum.The assay is intended for testing serumsamples from symptomatic patients or thosesuspected of Lyme Disease.Positive and equivocal test results with theZEUS ELISA Borrelia burgdorferi IgG TestSystem for the presence of Borrelia burgdorferiantibodies must be confirmed through additionaltesting by one of the following approaches:(1) Standard two-tier test methodology (STTT)using IgG Western blot testing following currentguidelines; or -(2) Modified two-tier test methodology using theZUES ELISA Borrelia VIsE1/pepC10 IgG/IgMTest System.Positive test results by either the STTT or MTTTmethodology are supportive evidence for thepresence of antibodies and exposure to Borreliaburgdorferi, the cause of Lyme disease.A diagnosis of Lyme disease should be madebased on the presence of Borrelia burgdorferiantibodies history, symptoms and otherlaboratory data. | |
| Results | Qualitative |
| Same |
COMPARISON TO PREDICATE DEVICE
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| Characteristic | Candidate DeviceLIAISON® Lyme IgG | Predicate DeviceZEUS ELISABorrelia burgdorferi IgM Test System –K895292/K191398 |
|---|---|---|
| Measurand | IgG antibodies to Borrelia burgdorferi | Same |
| IntendedPopulation | Patients with signs and symptomsconsistent with Borrelia infection(Lyme disease) | Same |
| AssayPrinciple | Uses Borrelia antigens coated on a solid phaseto capture specific patient IgG antibodies. | Uses B. burgdorferi antigen on coatedsolid phase (wells) to bind withIgG antibodies in patient sample |
| Conjugateantibodyspecificities | Anti-human IgG | Same |
| Assay Output | Index | Same |
| Table 2: Table of Differences | ||
|---|---|---|
| Feature | Candidate DeviceLIAISON® Lyme IgG | Predicate DeviceZEUS ELISABorrelia burgdorferi IgM Test System –K895292/K191398 |
| Test Format | CLIA (indirect chemiluminescentassay) | ELISA |
| Sample Type | Human serum, serum separatortubes, K2-EDTA, lithium heparin plasma | Human serum |
| Reporter Molecule | Isoluminol derivative conjugated toanti-human IgG | TMB (as a substrate for Horseradishperoxidase conjugated to anti-human IgG). |
| Antigen | Recombinant antigens:VIsE ( B. burgdorferi strain B31)Peptide for C6 region of VIsE | Whole cell antigen fromB. burgdorferi (B31 strain) |
| Assay Procedure | Automated(on the LIAISON® XL Analyzer) | Manual |
| Calibration | Two-point verification (in triplicate) ofstored 10 point master curve | Single Cut-off Calibrator assayed in triplicate |
| Output Signal | Flash chemiluminescent response isintegrated over a 3 second readingperiod to generate a relative light unit | Microtiter well O.D. (450 nm) is measuredafter the enzyme reaction is halted by1M H2SO4/0.7M HCl. |
| MeasurementSystem | Photomultiplier(flash chemiluminescence reader) | Spectrophotometer(EIA Microtiter plate reader) |
PERFORMANCE DATA: METHOD COMPARISON:
Two thousand six hundred twenty one (2621) human serum specimens were collected in 14 states which represented five (5) distinct U.S. geographical regions. Of the 2621 samples: 44.1% were male, 55.7% were female, 0.2% gender unknown, the ages ranged from 2 years to 103 years of age.
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Testing with the LIAISON® Lyme IgG assay on the LIAISON® XL was performed in three (3) laboratories (2 external and internally at DiaSorin).
| Predicate Assay (ELISA IgG) | ||||
|---|---|---|---|---|
| LIAISON Lyme IgG | Positive | Equivocal | Negative | Total |
| Positive | 156 | 4 | 86 | 246 |
| Equivocal | 6 | 0 | 24 | 30 |
| Negative | 119 | 16 | 2210 | 2345 |
| Total | 281 | 20 | 2320 | 2621 |
| Table 3: First Tier Percent Agreement with Predicate Device | ||||
|---|---|---|---|---|
| -- | -- | -- | -- | ------------------------------------------------------------- |
Agreement Results
| Positive % Agreement* | 55.1% (166/301) | 95% CI: 49.5% - 60.7% |
|---|---|---|
| Negative % Agreement | 96.5% (2210/2320) | 95% CI: 94.3% - 96.1% |
| *Includes Positive and Equivocal combined |
Standard Two-Tier Testing Methodology:
Western blot testing was performed on the samples that were positive or equivocal by the test device and the predicate following the current quidelines for Standard Two-Tier testing methodology. The following results were obtained:
| Table 4: Standard Two-Tier Western Blot | ||
|---|---|---|
| Test System | Tier 1 + or Eqv | WB IgG + | WB IgG - |
|---|---|---|---|
| Predicate assay | 301 | 109 | 192 |
| LIAISON® Lyme IgG | 276 | 109 | 167 |
| Predicate assay + LIAISON® Lyme IgG | 166 | 97 | 69 |
Agreement Results:
| 2nd Tier PPA | 89.0% (97/109) | 95%CI: 81.7% - 93.6% |
|---|---|---|
| 2nd Tier NPA | 99.5% (2500/2512) | 95%CI: 99.2% - 99.7% |
Modified Two Tier Testing Methodology – Prospective Population
All 2621 prospective (all comer) specimens were tested with the first-tier assay, LIAISON® Lyme Total Antibody Plus. There were 202 positive and 23 equivocal results. In the STTT protocol, the specimens that are positive or equivocal (n=225) are then tested with a B. burgdorferi (IgG) Western Blot.
Using the MTTT algorithm, the positive/equivocal specimens (n=225) were tested on the LIAISON® Lyme IgG assay. The second-tier LIAISON® Lyme IgG equivocal and positive results were considered positive. The equivocal and positive results were added together, and the results compared with the STTT positive results. The results obtained are shown in Table 5.
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| WB-STTT (IgG) | ||||
|---|---|---|---|---|
| + | - | Total | ||
| XL -MTTT (IgG) | + | 93 | 90 | 183 |
| - | 3 | 39 | 42 | |
| Total | 96 | 129 | 225 |
Table 5: MTTT | IAISON | vme lgG compared to STTT WB lgG
Agreement Results
| PPA: | 96.9% (93/96) | 95% CI: 91.2% - 98.9% |
|---|---|---|
| NPA: | 30.2% (39/129) | 95% CI: 23.0% - 38.6% |
Characterized Lyme Panel:
Two hundred eighty samples of various reactivity were acquired from the CDC and evaluated internally at the manufacture's site. The results of the testing are presented here as a means of conveying further information on the performance of the LIAISON® Lyme IgG assay with a characterized serum panel. This does not imply an endorsement of the assay by the CDC.
| CDC Reference Classification | ||||||||
|---|---|---|---|---|---|---|---|---|
| Sample Category | N | LIAISON Lyme IgG | Predicate IgG | |||||
| Pos | Neg | Eqv | Pos | Neg | Eqv | PPA95% Wilson CI | ||
| Acute | 39 | 28 | 10 | 1 | 23 | 15 | 1 | 74.4% (29/39)58.9% - 85.4% |
| Convalescent | 31 | 29 | 2 | 0 | 22 | 6 | 3 | 93.5% (29/31)79.3% - 98.2% |
| Late | 20 | 20 | 0 | 0 | 20 | 0 | 0 | 100% (20/20)83.9% - 100% |
| Look-alike Diseases | 90 | 9 | 81 | 0 | 9 | 77 | 4 | 90% (81/90)82.1% - 94.6% |
| Healthy controls | 100 | 3 | 97 | 0 | 1 | 98 | 1 | 97.0% (97/100)91.5% - 99.0% |
Table 6: Testing of CDC Lyme Reference Sera
Modified Two Tier Testing Methodology-Retrospective population
The 280 retrospective samples from the CDC were first tested with the LIAISON® Lyme Total Antibody Plus. One (1) sample, belonging to endemic negative control group, did not have sufficient volume for testing; therefore 279 retrospective samples were evaluated. The LIAISON® Lyme Total Antibody Plus assay vielded 82 positive and equivocal samples. The 82 positive and equivocal samples were then tested by the IgG Western Blot (STTT) or the LIAISON® Lyme IgG assay (MTTT).
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| Stage I (n=60) | Stage II (n=10) | Stage III (n=20) | Healthy Controls (n=99) | Disease Controls (n=90) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| STTT-WB IgG | MTTT-XL IgG | STTT-WB IgG | MTTT-XL IgG | STTT-WB IgG | MTTT-XL IgG | STTT-WB IgG | MTTT-XL IgG | STTT-WB IgG | MTTT-XL IgG | |
| Positive | 18 | 48 | 5 | 9 | 20 | 20 | 0 | 0 | 0 | 2 |
| Negative | 42 | 12 | 5 | 1 | 0 | 0 | 99 | 99 | 90 | 88 |
| Sensitivity or PPA | 30% | 80% | 50% | 90% | 100% | 100% | N/A | N/A | N/A | N/A |
| Specificity or NPA | N/A | N/A | N/A | N/A | N/A | N/A | 100% | 100% | 100% | 97.8% |
The results of MTTT-IqG compared to WB-STTT (IgG) are in the following table.
PRECISION STUDY
A 12 day precision/repeatability was conducted at DiaSorin Inc. on two (2) lots of the LIAISON® Lyme IgG assay. Six (6) serum samples and two (2) lots of LIAISON® Lyme IgG Controls were tested for 12 days, 2 runs/day, and 2 reps per run by multiple technicians for a total of 48 replicates per lot spanning 2 calibration cycles. One (1) lot is presented below. The CLSI Document EP5-A3 was consulted in the preparation of the testing protocol.
| Sample ID | N | Mean | Within Run | Between Run | Between Day | TOTAL(Within-lot) | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| Negative Control Lot V1 | 48 | 0.46 | 0.02 | 4.2% | 0.02 | 4.7% | 0.00 | 0.0% | 0.03 | 5.9% |
| Positive Control Lot V1 | 48 | 2.22 | 0.10 | 4.4% | 0.11 | 4.8% | 0.03 | 1.5% | 0.15 | 6.7% |
| Negative Control LotV2 | 48 | 0.09 | 0.00 | 4.1% | 0.00 | 3.5% | 0.00 | 4.7% | 0.01 | 7.2% |
| Positive Control Lot V2 | 48 | 2.39 | 0.07 | 2.9% | 0.21 | 8.6% | 0.00 | 0.0% | 0.17 | 7.2% |
| LG-QC1 | 48 | 0.77 | 0.03 | 3.9% | 0.04 | 5.4% | 0.00 | 0.0% | 0.05 | 6.1% |
| LG-QC3 | 48 | 1.37 | 0.04 | 2.7% | 0.05 | 3.8% | 0.04 | 2.7% | 0.07 | 5.4% |
| LG-QC4 | 48 | 4.89 | 0.11 | 2.3% | 0.11 | 2.3% | 0.11 | 2.2% | 0.19 | 3.9% |
| LG-QC5 | 48 | 0.82 | 0.05 | 6.4% | 0.04 | 5.2% | 0.04 | 5.4% | 0.08 | 9.8% |
| LG-QC6 | 48 | 1.47 | 0.05 | 3.3% | 0.06 | 4.2% | 0.00 | 0.0% | 0.08 | 5.2% |
| LG-QC7 | 48 | 0.48 | 0.02 | 3.3% | 0.01 | 1.7% | 0.01 | 2.3% | 0.02 | 4.4% |
REPRODUCIBILITY STUDY
A five (5) day precision/reproducibility study was performed internally at DiaSorin Inc. and at two (2) external U.S. laboratories with one (1) lot of the LIAISON® Lyme IgG assay.
The study was performed for 5 days, 2 runs/day, and 3 replicates/run. Each day, two operators, at each testing site performed the testing for a total of 30 replicates at each site. The combined results from the 3 sites are provided. CLSI document EP15-A3 was consulted in the preparation of the testing protocol.
| SampleID | n | mean | Within Run | Between Day | Between Run | Between Site | TOTAL | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||
| Negative Control | 90 | 0.128 | 0.006 | 4.3% | 0.004 | 3.3% | 0.00 | 0.0% | 0.006 | 4.8% | 0.009 | 7.3% |
| Positive Control | 90 | 2.25 | 0.064 | 2.9% | 0.048 | 2.1% | 0.037 | 1.7% | 0.113 | 5.0% | 0.144 | 6.4% |
| LG-QC1 | 90 | 0.820 | 0.018 | 2.2% | 0.032 | 4.0% | 0.016 | 2.0% | 0.043 | 5.3% | 0.060 | 7.3% |
| LG-QC3 | 90 | 1.40 | 0.039 | 2.8% | 0.035 | 2.5% | 0.041 | 2.9% | 0.039 | 2.8% | 0.077 | 5.5% |
| LG-QC4 | 90 | 5.05 | 0.113 | 2.2% | 0.142 | 2.8% | 0.068 | 1.3% | 0.203 | 4.0% | 0.280 | 5.5% |
| LG-QC5 | 90 | 0.735 | 0.021 | 2.8% | 0.030 | 4.1% | 0.017 | 2.2% | 0.034 | 4.6% | 0.053 | 7.2% |
| LG-QC6 | 90 | 1.63 | 0.048 | 3.0% | 0.029 | 1.8% | 0.035 | 2.1% | 0.065 | 4.0% | 0.092 | 5.7% |
| LG-QC7 | 90 | 0.542 | 0.013 | 2.5% | 0.020 | 3.7% | 0.006 | 1.1% | 0.033 | 6.2% | 0.041 | 7.7% |
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CROSS-REACTIVITY STUDY
The cross-reactivity study was designed to evaluate 222 specimens from twenty-two (22) disease states either known to contain potentially cross reactive antibodies to B. burgdorferi or from patients with diagnoses that can exhibit signs and symptoms similar to Lyme disease and cause false positive results.
| Organism/Disease State | SamplesTested(n) | LIAISON® Lyme IgGPos or Eqv |
|---|---|---|
| Tick Borne Diseases* | ||
| Babesiosis IgG | 10 | 5 |
| Autoimmune Disorders | ||
| Anti-Nuclear Antibodies (ANA) | 10 | 0 |
| Multiple Sclerosis | 10 | 0 |
| Viral Diseases | ||
| Cytomegalovirus (CMV) IgG | 10 | 0 |
| Epstein-Barr Virus (EBV) IgG | 10 | 0 |
| Epstein-Barr Virus (EBV) EBNA IgG | 10 | 1 |
| Epstein-Barr Virus (VCA) IgG | 10 | 0 |
| Herpes Simplex Virus (HSV) IgG | 10 | 0 |
| Human Immunodeficiency Virus (HIV) | 10 | 0 |
| Influenza Virus | 10 | 0 |
| Parvovirus IgG | 10 | 0 |
| Varicella Zoster Virus (VZV) IgG | 10 | 0 |
| Bacterial Diseases | ||
| H. pylori | 10 | 1 |
| Syphilis | 10 | 0 |
| Leptospirosis | 2 | 1 |
| Rheumatic Diseases | ||
| Fibromyalgia | 10 | 0 |
| Rheumatoid Arthritis | 10 | 0 |
| Rheumatoid Factor | 10 | 0 |
| Systemic Lupus Erythematosus (SLE) | 10 | 0 |
| Sjogrens Syndrome | 10 | 1 |
| Additional Markers | ||
| Chronic Fatigue Syndrome | 10 | 1 |
| Human Anti-mouse Antibodies (HAMA) | 10 | 0 |
| E. coli | 10 | 0 |
| Total | 222 | 10 |
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INTERFERING SUBSTANCES
"Controlled studies of potentially interfering substances from endogenous interferents spiked into serum specimens containing B. burgdorferi IgG antibodies at levels near the cut-off showed that assay performance was not affected at the concentration for each substance listed below. The testing was based on CLSI-EP7-A3.
| Substances | TestedConcentrations |
|---|---|
| Hemoglobin | 1000 mg/dL |
| Triglycerides | 1500 mg/dL |
| Bilirubin | 40 mg/dL |
| Total protein | 15 g/dL |
| Cholesterol | 400 mg/dL |
| Biotin | 3600 ng/mL |
MATRIX EQUIVALENCE STUDY:
Thirty-two (32) matched patient sets of serum, SST serum, K2-EDTA plasma and lithium heparin plasma samples were tested to determine if these sample types provide equivalent results. Sample regression analysis was done by Passing & Bablok regression. All sample types met acceptance criteria for use in the LIAISON® Lyme IgG assay. A summary of the results are shown in the following table.
| Comparison to Serum | Bias | 95% Cl | |
|---|---|---|---|
| Serum SST | Constant | -0.01 | -0.04 to 0.00 |
| Proportional | 1.04 | 1.01 to 1.10 | |
| EDTA Plasma | Constant | 0.00 | -0.01 to 0.03 |
| Proportional | 0.96 | 0.93 to 1.01 | |
| Lithium Heparin Plasma | Constant | 0.01 | -0.04 to 0.04 |
| Proportional | 0.97 | 0.91 to 1.03 |
CONCLUSION:
The material submitted in this premarket notification supports a substantial equivalence decision. The labelling satisfies the requirements of 21CFR 809.10.
§ 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).