(90 days)
Not Found
No
The summary describes a flow immunoassay kit and its performance characteristics, with no mention of AI or ML in the device description, intended use, or performance studies.
No
This device is an in vitro diagnostic (IVD) device used for the qualitative detection of antibodies to Borrelia burgdorferi for Lyme disease diagnosis, which is a diagnostic purpose, not a therapeutic one.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the qualitative detection of total (lgM/IgG) antibodies to Borrelia burgdorferi in human serum and plasma" and "should be used to test patients with a history and/ or symptoms of infection with B. burgdorferi." Furthermore, it details how the results contribute to the "diagnosis of Lyme borreliosis," clearly indicating its role in the diagnostic process.
No
The device description clearly outlines physical components including vials of Bead Set, Conjugate, and Sample Diluent, which are chemical reagents used in a laboratory assay. It also mentions required materials like Sheath Fluid and Wash Solution. This indicates a physical kit used in conjunction with the Bio-Rad BioPlex 2200 System, not a standalone software device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the kit is "intended for the qualitative detection of total (lgM/IgG) antibodies to Borrelia burgdorferi in human serum and plasma". This clearly indicates that the device is used to examine specimens derived from the human body (serum and plasma) to provide information for diagnostic purposes (detecting antibodies related to Lyme disease).
- Device Description: The description details the components of a kit designed to perform a laboratory test on biological samples.
- Performance Studies: The document describes various performance studies (Precision, Reproducibility, Analytical Specificity, Interfering Substances, Cross-Reactivity, Matrix comparison, Method Comparison, Sensitivity, CDC Panel) which are typical evaluations conducted for IVD devices to demonstrate their analytical and clinical performance.
- Predicate Device: The mention of a "Predicate Device" (K003754; Immunetics C6 B. burgdorferi (Lyme) ELISA Kit) is a strong indicator that this device is being compared to an already cleared IVD device, which is a common practice in the regulatory submission process for new IVDs.
All these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The BioPlex 2200 Lyme Total kit is a multiplex flow immunoassay intended for the qualitative detection of total (IgM/IgG) antibodies to Borrelia burgdorferi in human serum and plasma (EDTA, heparin). This assay should be used to test patients with a history and/ or symptoms of infection with B. burgdorferi. The BioPlex 2200 Lyme Total assay is intended for use with the Bio-Rad BioPlex 2200 System. All reactive and equivocal specimens should be tested with a second tier test such as Lyme IgM and IgG Western blot assays. Positive second tier results are supportive evidence of infection with B. burgdorferi. Diagnosis of Lyme borreliosis should be made based on the presence of B. burgdorferi antibodies, history, symptoms, and other laboratory data. Non-reactive first tier or negative second tier results should not be used to exclude borreliosis.
Product codes
LSR
Device Description
BioPlex 2200 Lyme Total kit includes the following components:
- One (1) 10 mL vial of Bead Set , containing dyed beads coated with recombinant p58, OspC ● type B (OspCB) and synthetic peptide FVlsE (consisting of FlaB and VlsE sequences), an Internal Standard bead (ISB) and a Serum Verification bead (SVB) in MOPS (3-[N-Morpholino] propane sulfonic acid) buffer containing bovine proteins with protein stabilizers. BND (5-bromo-5-nitro-1,3-dioxan) (≤ 0.1%), ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide ( 12 months, N=7): 85.7% (6/7) (95% CI 42.1 — 99.6%)
- Total (N=105): 68.6% (72/105) (95% CI 58.8 — 77.3%)
CDC Panel:
Sample Size: 280 positive and negative specimens.
Key Results:
Agreement with Clinical Diagnosis:
- Acute (N=39): 84.6%
- Convalescent (N=31): 93.5%
- Late (N=20): 100%
- Look-alike Diseases (N=90): 96.7%
- Healthy Controls (N=100): 97.0%
Comparative Testing of CDC Reference Sera:
- Early EM Acute (N=30): BioPlex 2200 Lyme Total 80.0% agreement, Commercial Lyme IgM/IgG Immunoassay 63.3% agreement.
- Early EM Convalescent (N=30): BioPlex 2200 Lyme Total 93.3% agreement, Commercial Lyme IgM/IgG Immunoassay 90.0% agreement.
- Cardiac Lyme Acute (N=3): BioPlex 2200 Lyme Total 100% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Neurological Lyme Acute (N=6): BioPlex 2200 Lyme Total 100% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Neurological Lyme Convalescent (N=1): BioPlex 2200 Lyme Total 100% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Lyme Arthritis/Neuro Late (N=20): BioPlex 2200 Lyme Total 100% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Fibromyalgia (N=15): BioPlex 2200 Lyme Total 93.3% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Rheumatoid arthritis (N=15): BioPlex 2200 Lyme Total 100% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Multiple sclerosis (N=15): BioPlex 2200 Lyme Total 100% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Mononucleosis (N=15): BioPlex 2200 Lyme Total 86.7% agreement, Commercial Lyme IgM/IgG Immunoassay 86.7% agreement.
- Syphilis (N=15): BioPlex 2200 Lyme Total 100% agreement, Commercial Lyme IgM/IgG Immunoassay 93.3% agreement.
- Periodontitis (N=15): BioPlex 2200 Lyme Total 100% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Endemic Negative Controls (N=50): BioPlex 2200 Lyme Total 96.0% agreement, Commercial Lyme IgM/IgG Immunoassay 100% agreement.
- Non-Endemic Negative Controls (N=50): BioPlex 2200 Lyme Total 98.0% agreement, Commercial Lyme IgM/IgG Immunoassay 98.0% agreement.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement (PPA): 70.1% (68/97) (95% CI 60.0 - 79.0%) from Method Comparison Study.
Negative Percent Agreement (NPA): 95.1% (661/695) (95% CI 93.2 - 96.6%) from Method Comparison Study.
Sensitivity (overall): 68.6% (72/105) (95% CI 58.8 — 77.3%) from Sensitivity Study.
Analytical Specificity: 96.4% (Asymptomatic Non-Endemic) and 96.4% (Asymptomatic Endemic).
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and the word "ADMINISTRATION" in a smaller font below.
March 12, 2019
Bio-Rad Laboratories Arlene Carillo RA Manager 5500 East Second Street Benicia, California 94510
Re: K183446
Trade/Device Name: BioPlex 2200 Lyme Total Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema pallidum treponemal test reagents Regulatory Class: Class II Product Code: LSR Dated: December 11, 2018 Received: December 12, 2018
Dear Arlene Carillo:
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 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
1
- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
for
Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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BioPlex 2200 Lyme Total 510(k) Summary
Bio-Rad Laboratories hereby submits this 510(k) in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. This summary of 510(k) safety and effectiveness information provides detail as a basis for a determination of substantial equivalence for the BioPlex 2200 Lyme Total kit.
510(k) Number: K183446
Summary Preparation Date: December 11, 2018
Applicant: Bio-Rad Laboratories
Contact: Arlene Carillo Regulatory Affairs Manager 5500 East Second Street Benicia, CA 94510
Measurand: Anti-Borrelia burgdorferi (IgM and IgG) antibodies
Type of Test: Quantitative multiplexed flow immunoassay
Proprietary and Established Names:
BioPlex 2200 Lyme Total
Regulatory Information:
-
Regulation section: 21 CFR 866.3830; Treponema pallidum treponemal test reagents
-
Classification: Class II
-
- Product code: LSR; Reagent, Borrelia Serological Reagent
-
- Panel: Microbiology (83)
Intended Use:
Intended use(s):
The BioPlex 2200 Lyme Total kit is a multiplex flow immunoassay intended for the qualitative detection of total (lgM/IgG) antibodies to Borrelia burgdorferi in human serum and plasma (EDTA, heparin). This assay should be used to test patients with a history and/ or symptoms of infection with B. burgdorferi. The BioPlex 2200 Lyme Total assay is intended for use with the Bio-Rad BioPlex 2200 System. All reactive and equivocal specimens should be tested with a second tier test such as Lyme IgM and IgG Western blot assays. Positive second tier results are
3
supportive evidence of infection with B. burgdorferi. Diagnosis of Lyme borreliosis should be made based on the presence of B. burgdorferi antibodies, history, symptoms, and other laboratory data. Non-reactive first tier or negative second tier results should not be used to exclude borreliosis.
Device Description:
BioPlex 2200 Lyme Total kit includes the following components:
- One (1) 10 mL vial of Bead Set , containing dyed beads coated with recombinant p58, OspC ● type B (OspCB) and synthetic peptide FVlsE (consisting of FlaB and VlsE sequences), an Internal Standard bead (ISB) and a Serum Verification bead (SVB) in MOPS (3-[N-Morpholino] propane sulfonic acid) buffer containing bovine proteins with protein stabilizers. BND (5-bromo-5-nitro-1,3-dioxan) (≤ 0.1%), ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (Borrelia burgdorferi in human serum and plasma (EDTA, heparin). This assay should be used to test patients with history and/or symptoms of infection with B. burgdorferi . The BioPlex 2200 Lyme Total assay is intended for use with the Bio-Rad BioPlex 2200 System. All reactive and equivocal specimens should be tested with a second tier test such as Lyme IgM and IgG Western blot assays. Positive second tier results are supportive evidence of infection with B. burgdorferi . Diagnosis of Lyme borreliosis should be made based on the presence of B. burgdorferi antibodies, history, symptoms, and other laboratory data. Non-reactive first tier or negative second tier results should not be used to exclude borreliosis. | The Immunetics C6 B. burgdorferi (Lyme) ELISA Kit is intended for use in the presumptive detection of IgG and IgM antibodies to B. burgdorferi in human serum. The assay should be used only on samples from patients with clinical history, signs or symptoms consistent with B. burgdorferi infection, including individuals who have received the licensed recombinant OspA Lyme disease vaccine (Lymerix). Positive or equivocal results should be supplemented by testing with a standardized Western Blot (second step) method. Positive Western Blot results provide evidence for exposure to or infection with B. burgdorferi . The diagnosis of Lyme disease must be made based on history, signs (such as erythema migrans), symptoms, and other laboratory data, in addition to the presence of antibodies to B. burgdorferi . Negative results (either first or second step) should not be used to exclude Lyme disease. |
| Measured
Analyte | Anti- Borrelia burgdorferi (IgM and IgG) antibodies | Same |
| Assay Type | Qualitative | Qualitative |
5
| Characteristics | Device Differences | |
|---|---|---|
| New Device | ||
| BioPlex 2200 Lyme Total | Predicate Device | |
| Immunetics C6 B. burgdorferi | ||
| (Lyme) ELISA Kit, K003754 | ||
| Assay Technology | Automated multiplex flow competitive | |
| immunoassay | ELISA (enzyme-linked | |
| immunosorbent assay) | ||
| Antigen | Recombinant p58, OspC type B (OspCB) | |
| and synthetic peptide FVIsE | Synthetic peptide (C6 peptide) | |
| Signal Detection | Fluorescence | Optical density readings from |
| Spectrophotometer | ||
| Solid Phase | Antigen-coated paramagnetic microbeads | Antigen-coated microwell |
| Conjugate | Murine monoclonal anti-human IgG, murine | |
| monoclonal anti-human IgM and | ||
| phycoerythrin conjugated murine monoclonal | ||
| anti-human FXIII antibody | Horseradish peroxidase- | |
| conjugated (HRP) goat anti- | ||
| human IgG/IgM conjugate | ||
| Sample Size | 5 μL | 10 μL |
| Sample | ||
| Handling/Process | Automated | Manual |
| Unit of Measure | Antibody Index (AI) | Lyme Index (LI) |
| Sample Matrix | Serum and plasma | Serum |
| Instrumentation | Bio-Rad BioPlex 2200 System | None (Manual) |
Test Principle: The BioPlex 2200 Lyme Total kit employs fluoromagnetic, dyed beads which are coated with recombinant p58, OspCB or synthetic peptide FVIsE. Unique fluorescent signatures identify the presence of total (IgM/IgG) antibodies to B. burgdorferi in a two-step assay format.
The BioPlex 2200 System combines an aliquot of patient sample diluent, and bead reagent in a reaction vessel. The mixture is incubated at 37°C. After a wash cycle, a mixture of murine monoclonal anti-human IgG and murine monoclonal anti-human IgM antibody conjugated to phycoerythrin (PE) is added to the dyed beads, and this mixture is incubated at 37°C. The excess conjugate is removed in another wash cycle and the beads are re-suspended in sheath fluid. The bead mixture then passes through the detector. The identity of the dyed beads is determined by the fluorescence of the dyes, and the amount of antibody captured by the antigen is determined by the fluorescence of the attached PE. Raw data is calculated in relative fluorescence intensity (RFI).
Two additional dyed beads, an Internal Standard Bead (ISB) and a Serum Verification Bead (SVB), are present in each reaction mixture to verify detector response and the addition of serum or plasma to the reaction vessel respectively. Refer to the BioPlex 2200 System Operation Manual for more information.
The system is calibrated using a set of three (3) distinct calibrator vials supplied separately by Bio-Rad Laboratories. One vial contains negative sample, and the other two vials contain human B. burgdorferi sensu stricto antibodies, which are used for qualitative calibration of the assays. The qualitative results
6
are expressed in an antibody index (AI). The assay results are reported as nonreactive, equivocal or reactive.
Performance Characteristics
Non-Clinical Studies
Assay Cut-Off: A total of 1.372 normal sera were used to determine the percentile cut-off in increments of 1/1000th for each analyte. Based on a retrospective selection of around the 98th percentile, the relative fluorescence intensity (RFI) corresponding to the chosen cutoff was assigned a value of 1.0 AI, and subsequently evaluated for performance against clinically diagnosed samples. The statistics show that the 98th percentile cutoff meets the minimum agreement specifications while maximizing the clinical specificity. The assay employs an equivocal zone that brackets the cut-off (0.9-1.0 AI), with samples ≥1.1 AI reported as reactive and ≤0.8 AI reported as non-reactive.
Precision Study: Precision testing of the BioPlex 2200 Lyme Total kit was performed in accordance with the Clinical and Laboratory Standards Institute (CLSI) EP5-A3 guideline. The serum samples were tested in duplicate, two runs per day, over 20 days (2 replicates x 2 runs x 20 days = 80 replicates per panel member) using one lot of the BioPlex 2200 Lyme Total Reagent Pack, Calibrator Set and Control Set. The results are summarized in the table below.
| | | | | Within Run
(Repeatability) | | Between
Run | | Between
Day | | Total | |
|----------------|-----------------------|----|--------------|-------------------------------|------|----------------|------|----------------|------|-------|------|
| Sample
Type | Sample
Description | N | Mean
(AI) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Serum | High
Negative 1 | 80 | 0.7 | 0.032 | 4.5% | 0.000 | 0.0% | 0.015 | 2.1% | 0.035 | 4.9% |
| | High
Negative 2 | 80 | 0.9 | 0.050 | 5.4% | 0.000 | 0.0% | 0.010 | 1.1% | 0.051 | 5.5% |
| | Cut-Off | 80 | 1.0 | 0.040 | 3.9% | 0.000 | 0.0% | 0.030 | 2.8% | 0.050 | 4.8% |
| | Low
Positive | 80 | 1.5 | 0.040 | 2.7% | 0.032 | 2.1% | 0.031 | 2.1% | 0.060 | 4.0% |
| | Mid Positive | 80 | 2.8 | 0.081 | 2.9% | 0.071 | 2.5% | 0.039 | 1.4% | 0.114 | 4.1% |
| | High
Positive | 80 | 4.7 | 0.288 | 6.1% | 0.000 | 0.0% | 0.139 | 3.0% | 0.320 | 6.8% |
BioPlex 2200 Lyme Total Precision
Reproducibility Study: To assess reproducibility of the BioPlex 2200 Lyme Total kit, a reproducibility panel was prepared at Bio-Rad Laboratories. The panel contained members with varying levels of antibodies to the analytes in the BioPlex 2200 Lyme Total kit, and a positive control (antibody reactive for all analytes). Reproducibility testing was performed at 3 clinical trial sites. One lot of BioPlex 2200 Lyme Total Reagent Packs, BioPlex 2200 Lyme Total Calibrator Sets and BioPlex 2200 Lyme Total Control Sets was used to evaluate reproducibility. Each of the panel members and a positive and negative control were tested in quadruplicate on 2 runs per day over 5 days at each of 3 sites (4 replicates x 2 runs x 5 days = 40 replicates per panel member per site = 120 total replicates for 3 sites). The data was analyzed for intra-assay and inter-assay reproducibility according to the CLSI guidance EP15-A3. Results are shown in the table below.
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| Lyme Total
Panel Member | N | Mean
(AI) | Repeatability | | Between Run | | Between Day | | Between Site | | Total | |
|----------------------------|-----|--------------|---------------|------|-------------|------|-------------|------|--------------|------|-------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Low Negative | 120 | 0.4 | 0.020 | 5.1% | 0.000 | 0.0% | 0.004 | 1.0% | 0.006 | 1.5% | 0.022 | 5.4% |
| High Negative | 120 | 0.7 | 0.035 | 5.1% | 0.013 | 1.8% | 0.023 | 3.3% | 0.032 | 4.5% | 0.055 | 7.8% |
| Low Positive | 120 | 1.1 | 0.040 | 3.6% | 0.016 | 1.5% | 0.027 | 2.4% | 0.075 | 6.7% | 0.091 | 8.1% |
| Mid Positive | 120 | 1.8 | 0.049 | 2.7% | 0.000 | 0.0% | 0.024 | 1.3% | 0.111 | 6.2% | 0.124 | 7.0% |
| High Positive | 120 | 4.7 | 0.108 | 2.3% | 0.116 | 2.5% | 0.121 | 2.6% | 0.131 | 2.8% | 0.239 | 5.1% |
BioPlex 2200 Lyme Total Reproducibility
Analytical Specificity: Analytical specificity of the BioPlex 2200 Lyme Total kit was evaluated against 836 samples from asymptomatic individuals from endemic regions. These samples were obtained from an asymptomatic population and excluded pre-screened blood donors. The results, expressed as % negatives, are presented in the following table.
BioPlex 2200 Lyme Total Analytical Specificity
| | N | BioPlex 2200 Lyme Total | Commercial Lyme IgM/IgG
Immunoassay |
|-----------------------------|-----|--------------------------|----------------------------------------|
| Asymptomatic
Non-Endemic | 416 | 96.4% | 95.4% |
| Asymptomatic
Endemic | 420 | 96.4% | 94.8% |
Interfering Substances: An interfering substances study was conducted to evaluate the potential interference of specific endogenous and exogenous substances with the BioPlex 2200 Lyme Total kit according to CLSI EP07-A2 guideline. No interference was observed with any of the substances tested. The substances and the maximum levels tested are shown in the table below:
Interfering Substances
| Substance | Concentration |
|---|---|
| Hemoglobin | 1000 mg/dL |
| Bilirubin (unconjugated) | 20 mg/dL |
| Bilirubin (conjugated) | 30 mg/dL |
| Triglycerides | 3300 mg/dL |
| Total Protein | 12 g/dL |
| Cholesterol | 500 mg/dL |
| Ascorbic Acid | 6 mg/dL |
| EDTA | 800 mg/dL |
| Sodium Heparin | 8000 units/dL |
| Lithium Heparin | 8000 units/dL |
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Cross-Reactivity: A cross-reactivity study was performed to determine if samples from various disease states and other potentially cross-reacting agents interfere with test results when tested with the BioPlex 2200 Lyme Total kit. Samples known to be positive for each cross-reactant listed in the table below were evaluated with the BioPlex 2200 Lyme Total kit. All samples were pre-tested by a commercially available Lyme assay and only those that tested negative by the commercially available assay were further tested by the BioPlex 2200 Lyme Total kit. Percent negative agreement for each potential cross reactant is shown below.
| | Negative BioPlex 2200 Results/
Negative Commercial Lyme IgM/IgG
Immunoassay Results | | |
|---------------------------------------|-------------------------------------------------------------------------------------------|------------------------|--|
| Potential
Cross Reactant | N | %Negative
Agreement | |
| Anti-nuclear antibody (ANA) | 13/13 | 100% | |
| Babesiosis | 10/10 | 100% | |
| Chronic Fatigue Syndrome | 14/14 | 100% | |
| Cytomegalovirus | 13/13 | 100% | |
| Epstein-Barr Virus | 45/49 | 92% | |
| Ehrlichiosis | 10/11 | 91% | |
| HAMA | 13/13 | 100% | |
| Helicobacter pylori | 12/12 | 100% | |
| HIV | 13/13 | 100% | |
| Influenza virus | 14/15 | 93% | |
| Leptospirosis | 33/34 | 97% | |
| Multiple sclerosis | 14/14 | 100% | |
| Parvovirus B19 | 14/14 | 100% | |
| Periodontal | 34/35 | 97% | |
| Rheumatoid arthritis | 14/14 | 100% | |
| Rheumatoid Factor positive | 13/13 | 100% | |
| Rickettsial diseases | 16/16 | 100% | |
| Rubella | 14/14 | 100% | |
| Syphilis | 47/48 | 98% | |
| Systemic Lupus Erythematosus
(SLE) | 15/15 | 100% | |
| Toxoplasmosis | 29/29 | 100% | |
| Varicella Zoster Virus | 14/14 | 100% | |
Results of Cross-Reactivity Study
Matrix comparison: Matched serum and plasma (EDTA and heparin) samples drawn from the same donor were acquired through a vendor. A minimum of 40 sets of paired serum and plasma samples were prepared and values within the measurement range of the assay were analyzed. Samples were spiked with high titer Lyme samples to obtain concentrations that span the assay range. Samples were assayed in replicates of two with the second replicate run in reverse order. Mean plasma AI values were compared to matched mean serum AI values. Linear regression analysis was used to determine the presence of a matrix effect when compared to serum. The regression correlation parameters for
9
slope, intercept and correlation coefficient (r) are shown below.
| Matrix Comparison | N | Slope
(95% CI) | Intercept
(95% CI) | Correlation
(r) |
|---------------------------------|----|------------------------|-------------------------|--------------------|
| K2-EDTA
VS.
Serum | 77 | 1.02
(0.95 to 1.08) | 0.17
(-0.09 to 0.44) | 0.960 |
| K3-EDTA
VS.
Serum | 74 | 1.01
(0.93 to 1.08) | 0.14
(-0.14 to 0.42) | 0.951 |
| Sodium Heparin
VS.
Serum | 77 | 0.97
(0.91 to 1.02) | 0.09
(-0.13 to 0.30) | 0.970 |
| Lithium Heparin
VS.
Serum | 78 | 0.97
(0.92 to 1.01) | 0.05
(-0.12 to 0.22) | 0.981 |
BioPlex 2200 Lyme Total Matrix Comparison
Clinical Studies
Method Comparison Study: Performance of the BioPlex 2200 Lyme Total kit was evaluated using prospectively collected serum samples from patients submitted for Lyme disease testing originating from various geographically distinct locations in the U.S. A total of 792 serum samples were evaluated at three (3) U.S. clinical testing sites. Equivocal (Eqv.) samples are added to positives for calculating agreement results since they will be tested by the second tier Western blot. Results are shown in the table below.
BioPlex 2200 Lyme Total Percent Agreement with Predicate Device - 1* Tier
| | Commercial Lyme IgM/IgG
Immunoassay | | | | | |
|----------------------------|----------------------------------------|------|-----|-------------|-----------------------|--------------|
| | Pos | Eqv. | Neg | % Agreement | 95% CI | |
| BioPlex 2200
Lyme Total | Reactive | 65 | 0 | 30 | PPA = 70.1% (68/97) | 60.0 - 79.0% |
| | Eqv. | 2 | 1 | 4 | | |
| | Non-Reactive | 21 | 8 | 661 | NPA = 95.1% (661/695) | 93.2 - 96.6% |
| | Total | 88 | 9 | 695 | | |
PPA=positive percent agreement, NPA= negative percent agreement
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Second-Tier Testing: All reactive/positive and equivocal samples by the BioPlex 2200 Lyme Total kit and the commercially available predicate device were tested by FDAcleared IgG and IgM Western blot assays. Shown below are the second tier Western blot results (combined IgG and IgM) for samples that were reactive/ positive and equivocal in the prospective sample study.
| | Tier 1
- or ± | WB + | WB - |
|---------------------------------------------------------------------------|------------------|------|------|
| Commercial Lyme
IgM/IgG
Immunoassay | 97 | 47 | 50 |
| BioPlex 2200
Lyme Total | 102 | 49 | 53 |
| Commercial Lyme
IgM/IgG
Immunoassay +
BioPlex 2200
Lyme Total | 68 | 46 | 22 |
| Second Tier Testing and PPA Analysis | |||||
|---|---|---|---|---|---|
| -- | -- | -- | -- | -- | -------------------------------------- |
| 1st Tier PPA
(95% CI) | 70.1%
(60.0-79.0%) | 68/97 |
|--------------------------|-----------------------|-------|
| 2nd Tier PPA
(95% CI) | 97.9%
(88.7-99.9%) | 46/47 |
Sensitivity Study: Sensitivity of the BioPlex 2200 Lyme Total kit was evaluated using 105 clinically characterized samples from an archived collection containing early, convalescent and late phases of Lyme disease. The table below shows the sensitivity of the BioPlex 2200 Lyme Total kit for each of the disease phases along with a commercial Lyme IgM/IgG immunoassay.
| BioPlex 2200 Lyme Sensitivity with respect to Disease Stage | ||
|---|---|---|
| Clinical Stage | N | BioPlex 2200 Lyme Total | | | Sensitivity
95% CI | Commercial Lyme IgM/IgG Immunoassay | | | Sensitivity
95% CI |
|-------------------------------|-----|-------------------------|-----------|------------------|-----------------------------------|-------------------------------------|-----------|----------|-----------------------------------|
| | | Reactive | Equivocal | Non-
Reactive | | Positive | Equivocal | Negative | |
| Acute
( 12 months) | 7 | 6 | 0 | 1 | 85.7%
(6/7)
42.1 — 99.6% | 5 | 0 | 2 | 71.4%
(5/7)
29.0 — 96.3% |
| Total | 105 | 72 | 0 | 33 | 68.6%
(72/105)
58.8 — 77.3% | 64 | 1 | 40 | 61.9%
(65/105)
51.9 — 71.2% |
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CDC Panel: A panel of 280 positive and negative specimens from the Centers for Disease Control and Prevention (CDC) was tested for the presence of Lyme antibodies using the BioPlex 2200 Lyme Total kit. The results are presented as a means to convey further information on the performance of the BioPlex 2200 Lyme Total kit with a masked, characterized serum panel. This does not imply an endorsement of the BioPlex 2200 Lyme Total kit by the CDC. Results are summarized in the table below.
| BioPlex 2200 Lyme Total | |||||
|---|---|---|---|---|---|
| (N=280) | N | Reactive | Equivocal | Non-Reactive | % Agreement with |
| Clinical Diagnosis | |||||
| Acute | 39 | 33 | 0 | 6 | 84.6% |
| Convalescent | 31 | 29 | 0 | 2 | 93.5% |
| Late | 20 | 20 | 0 | 0 | 100% |
| Look-alike Diseases | 90 | 1 | 2 | 87 | 96.7% |
| Healthy Controls | 100 | 1 | 2 | 97 | 97.0% |
BioPlex 2200 Lyme Total Testing of CDC Reference Sera
The CDC panel was further evaluated against the BioPlex 2200 Lyme Total kit and a commercially available predicate device. The results are summarized in the table below.
| BioPlex 2200 Lyme Total Comparative Testing of CDC Reference Sera | |||
|---|---|---|---|
| Sample Category
(N=280) | | N | BioPlex 2200 Lyme Total | | | | Commercial Lyme IgM/IgG
Immunoassay | | | |
|----------------------------|------------------------|----|-------------------------|-----|-----------|----------------|----------------------------------------|-----|------------|----------------|
| | | | R
(+) | Eqv | NR
(-) | %
Agreement | Pos
(+) | Eqv | Neg
(-) | %
Agreement |
| Early EM | Acute | 30 | 24 | 0 | 6 | 80.0% | 19 | 0 | 11 | 63.3% |
| | Convalescent | 30 | 28 | 0 | 2 | 93.3% | 27 | 0 | 3 | 90.0% |
| Cardiac Lyme | Acute | 3 | 3 | 0 | 0 | 100% | 3 | 0 | 0 | 100% |
| Neurological
Lyme | Acute | 6 | 6 | 0 | 0 | 100% | 6 | 0 | 0 | 100% |
| | Convalescent | 1 | 1 | 0 | 0 | 100% | 1 | 0 | 0 | 100% |
| Lyme
Arthritis/Neuro. | Late | 20 | 20 | 0 | 0 | 100% | 20 | 0 | 0 | 100% |
| Fibromyalgia | Look-alike
Diseases | 15 | 0 | 1 | 14 | 93.3% | 0 | 0 | 15 | 100% |
| Rheumatoid
arthritis | | 15 | 0 | 0 | 15 | 100% | 0 | 0 | 15 | 100% |
12
| Sample Category
(N=280) | N | BioPlex 2200 Lyme Total | | | | Commercial Lyme IgM/IgG
Immunoassay | | | | |
|-------------------------------------|--------------------|-------------------------|-----|-----------|----------------|----------------------------------------|-----|------------|----------------|-------|
| | | R
(+) | Eqv | NR
(-) | %
Agreement | Pos
(+) | Eqv | Neg
(-) | %
Agreement | |
| Multiple
sclerosis | 15 | 0 | 0 | 15 | 100% | 0 | 0 | 15 | 100% | |
| Mononucleosis | 15 | 0 | 2 | 13 | 86.7% | 2 | 0 | 13 | 86.7% | |
| Syphilis | 15 | 0 | 0 | 15 | 100% | 1 | 0 | 14 | 93.3% | |
| Periodontitis | 15 | 0 | 0 | 15 | 100% | 0 | 0 | 15 | 100% | |
| Endemic
Negative
Controls | Healthy
Normals | 50 | 0 | 2 | 48 | 96.0% | 0 | 0 | 50 | 100% |
| Non-Endemic
Negative
Controls | | 50 | 1 | 0 | 49 | 98.0% | 1 | 0 | 49 | 98.0% |
R= Reactive, NR= Nonreactive
Conclusion: The submitted information in this 510(k) Premarket Notification will support a determination of substantial equivalence for BioPlex 2200 Lyme Total. The clinical and non-clinical tests demonstrate that this device is safe and effective and performs as well as the legally marketed predicate device.
13
Indications for Use
510(k) Number (if known)
Device Name
Indications for Use (Describe)
Type of Use (Select one or both, as applicable)Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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