(113 days)
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No
The summary describes a standard immunoassay and data management system, with no mention of AI or ML in the device description, intended use, or performance studies.
No
Explanation: The device is an immunoassay for detecting antibodies to diagnose Lyme Borreliosis, not to treat it.
Yes
Explanation: The device is intended for the "qualitative detection of IgG class antibody to recombinant VISE-1 and the IgM class of antibody to synthetic pepC10 in human serum," which are markers for Lyme Borreliosis. It is specifically designed to aid in the "Diagnosis of Borreliosis" and is used in conjunction with other clinical information to make a diagnosis.
No
The device description explicitly states that the test system is comprised of the AtheNA Multi-Lyte test kit and the Luminex Corp instrument model number Luminex™ 200 IS and software version 3. This indicates the device includes both hardware (the test kit and the Luminex instrument) and software, not just software.
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 device is for the "qualitative detection of IgG class antibody to recombinant VISE-1 and the IgM class of antibody to synthetic pepC10 in human serum." This indicates that the device is used to test human samples in vitro (outside the body) to provide information about a person's health status (presence of antibodies related to Lyme Borreliosis).
- Device Description: The "Device Description" further clarifies that it is a "micro particle immunoassay intended for the qualitative detection of distinct IgG class antibody to VlsE-1 and distinct IgM antibody to pepC10." This describes a laboratory test performed on biological samples.
- Intended User / Care Setting: The "Intended User / Care Setting" states "in vitro diagnostic use only, prescription use only. Tested at hospital laboratories and a state Department of Health laboratory." This directly confirms its intended use as an in vitro diagnostic device in a clinical laboratory setting.
The entire description aligns with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or a congenital abnormality, or to determine the compatibility of tissues or organs, or to monitor therapeutic measures.
N/A
Intended Use / Indications for Use
The Zeus Scientific, Inc AtheNA Multi-Lyte Borrelia VISE-1/ pepC10 Plus Test System is a multiplexed sandwich immunoassay for the qualitative detection of IgG class antibody to recombinant VISE-1 and the IgM class of antibody to synthetic pepC10 in human serum. The AtheNA Multi-lyte Borrelia VISE-1/pepC10 Plus Test System is intended for use with the Luminex® 200 IS and the AtheNA Multi-Lyte data management package in testing serum samples from symptomatic patients or those with a history of Lyme Borreliosis. All positive specimens should be tested with a second-tier test such as Western Blot which if positive, is supportive evidence of infection with B.burgdorferi. Diagnosis of Borreliosis should be made based on the presence of B.burgdorferi antibodies, history, symptoms and other laboratory data. Negative first or second tier results should not be used to exclude Borreliosis. This kit is for in vitro diagnostic use only.
Product codes (comma separated list FDA assigned to the subject device)
LSR
Device Description
The AtheNA Multi-Lyte Borrelia VlsE-1/pepC10 Plus Test System is a micro particle immunoassay intended for the qualitative detection of distinct IgG class antibody to VlsE-1 and distinct IgM antibody to pepC10. The assay is a multiplexed immunoassay designed to simultaneously detect, distinguish and identify IgG reactivity to recombinant VISE-1 antigen and IgM reactivity to synthetic pepC10 antigen. The test system is comprised of the AtheNA Multi-Lyte test kit and the Luminex Corp instrument model number Luminex™ 200 IS and software version 3.
The AtheNA Multi-Lyte Borrelia VIsE-1/pepC10 Plus test system provides the following Components:
Reactive Reagents:
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- All reactive reagents contain sodium azide as a preservative at a concentration of 0.1% (w/v).
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- Multiplexed bead suspension 1. Ready to use, 5.5 mL bottle. The suspension contains separate distinguishable 5.6 micron polystyrene beads that are conjugated with recombinant VlsE1 antigen. The bead mix also contains one bead set designed to detect non-specific antibodies in the patient sample (if present) and four separate bead sets used for assay calibration.
-
- Multiplexed bead suspension 2. Ready to use, 5.5 mL bottle. The suspension contains separate distinguishable 5.6 micron polystyrene beads that are conjugated with the following antigens: recombinant VlsE-1 and synthetic pepC10.
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- Conjugate 1: Phycoerythrin conjugated goat anti-human IgG (y chain specific). Ready to use, 15 mL amber bottle.
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- Conjugate 2: Phycoervthrin conjugated goat anti-human IgM (μ chain specific). Ready to use, 15 mL amber bottle.
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- Human positive serum controls. Two, 0.2 mL vials.
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- Human negative serum control. One, 0.2 mL vial.
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- SAVe Diluent®. One 50 mL bottle containing phosphate-buffered-saline. Ready to use. NOTE: the sample diluent will change color in the presence of serum.
-
- Wash Buffer Concentrate: dilute 1 part concentrate + 9 parts deionized or distilled water. One bottle containing 10 X concentrate of phosphate buffered saline.
Non-Reactive Reagents:
-
- One, dilution plate
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- One, 96-well filtration plate for rinsing the microspheres
-
- Data Labels: One label is adhered to the inside lid of the kit box and a second label is inside the kit box.
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- Package Insert providing instructions for use
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- Calibration CD: a compact disc that includes all lot-specific kit calibration values required for specimen analysis and assay quality control
Instrument and Software
This assay is platform dependant and used in conjunction with the Luminex 100 IS and the AtheNA Multi-Lyte® Test System Data Analysis Package Version 3.0.
Materials required but not provided:
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- AtheNA Multi-Lyte® System (Luminex® instrument)
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- Pipettes capable of accurately delivering 10 to 200 µL
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- Multichannel pipette capable of accurately delivering (10 to 200 µL)
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- Reagent reservoirs for multichannel pipettes
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- Disposable pipette tips
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- Laboratory timer to monitor incubation steps
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- Small bath sonicator
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- Plate shaker capable of shaking at 800 RPM (optional for mixing)
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- Vacuum aspirator and vacuum manifold for washing the microspheres
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
1 to 94
Intended User / Care Setting
Prescription Use, in vitro diagnostic use. Clinical sites/hospital laboratories.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
A total of 410 prospective samples were tested at four sites for the presence of VISE-1 and pepC10 using the AtheNA Multi-Lyte Borrelia VlsE-1/pepC10 Plus test system and predicate ELISA test system commercially marketed for the detection of Borrelia burgdorferi IgG and IgM antibodies namely the Zeus Scientific Borrelia burgdorferi ELISA Test System. These samples were submitted for B. burgdorferi antibody testing, sequentially numbered and archived. All positive samples were furthered tested using western blot methodology to confirm reactivity. 342 retrospective samples, acquired from various sources, were tested at three sites. Additional testing consisted of 100 low prevalence population samples, 300 endemic and 300 non-endemic control samples, 246 random samples submitted for Borrelia burgdorferi antibodies, 229 characterized serum samples and a panel of 40 characterized samples acquired from the CDC.
Summary of Specimens Included in Study:
Site of Testing 1: 124 retrospective samples (previously screened positive by laboratory), 107 prospective samples (submitted for B.burgdorferi antibody testing)
Site of Testing 2: 118 retrospective samples (previously screened positive by laboratory), 103 prospective samples (submitted for B.burgdorferi antibody testing)
Site of Testing 3: 446 prospective samples (submitted for B.burgdorferi antibody testing in 2006), 150 endemic controls (samples from blood donors collected in endemic area (New England)), 150 non-endemic controls (samples from blood donors collected in non-endemic area (New Mexico)), 21 characterized samples (acute patients with clinical history of Borreliosis), 50 characterized samples (convalescent patients with clinical history of Borreliosis), 158 characterized samples (78 paired samples from acute & convalescent patients with clinical history of Borreliosis)
Site of Testing 4: 100 prospective samples (submitted for B.burgdorferi antibody testing), 100 non-endemic controls (samples collected in non-endemic area for testing non-infectious in nature), 150 endemic controls (samples from blood donors collected in endemic area (New England)), 150 non-endemic controls (samples from blood donors collected in non-endemic area (New Mexico))
Expected results:
Internal and external investigators assessed the device's performance with 756 masked samples prospectively collected from patients between the ages of 1 and 94 which were submitted for Lyme antibody testing. Site 1, a hospital laboratory located in the northeast tested 107 samples. Site 2, a hospital laboratory in the northeast tested 103 samples. The third clinical site was a state Department of Health located in the northeast. This facility tested 446 samples collected in the northeast. Demographics for 346 of the 756 samples were unavailable. Site 4, the manufacturer's research facility tested 100 samples collected in Connecticut.
AtheNA Multi-Lyte Vlse-1/pepC10 Results from Other Populations:
Characterized: 229 samples tested, 171/229 positive
Retrospective: 242 samples tested, 191/242 positive, age range 4-85
Endemic Controls: 300 samples tested, 38/300 positive
Non-Endemic Controls: 400 samples tested, 39/400 positive
Clinical studies consisted of 1,967 serum samples evaluated at a total of four US sites. The following populations were tested:
- Characterized Samples
- Prospective Population
- Retrospective Samples
- CDC Lyme Panel
- Endemic and Non-Endemic Control Samples
- Precision and Reproducibility
Study 1. Characterized Samples: 229 characterized serum samples were acquired and tested at a northeastern state Department of Health Laboratory. 21 samples were acute patients with a history of Borreliosis. 50 samples were from convalescent patients with a history of Borreliosis. 14 of these patients present with neurological, 2 with cardiac and 34 with arthritic symptoms, 79 samples were paired acute (culture proven, early acute Lyme disease) and early convalescent sera from these same patients.
Study 2. Prospective Population: A total of 756 unselected samples from patients with an order for a Lyme antibody test were included in the study. The samples submitted for Lyme antibody testing were sequentially numbered, de-identified and archived. After the collection, 103 samples were tested at a hospital laboratory located in the Mid-Atlantic, 100 samples were tested at a hospital laboratory in upper Connecticut, 107 samples were tested at a hospital laboratory in lower Connecticut and 446 samples were tested at a state Department of Health Lab also located in the northeast.
Study 3. Retrospective Samples believed to have screened positive for Borrelia burgdorferi antibodies were tested at two external sites. 124 samples were tested in a hospital facility in Connecticut and 118 samples were tested in a Pennsylvania hospital laboratory.
Study 4. CDC Characterized Lyme Panel: 40 samples of various reactivity were acquired from the CDC and evaluated internally at the manufacturer's site. 5 samples were from normal blood donors. 35 samples were from patients diagnosed with Borreliosis.
Study 5. Analytical Specificity: Testing of normal population was done on 300 samples acquired from blood donors in the New England endemic area and 400 samples acquired from blood donors and individuals undergoing routine testing not infectious in nature in the New Mexico non-endemic area.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Performance
Linearity:
A strong positive sample was determined using a FDA cleared test system to determine the sample reactivity. A fresh, clean, dead negative sample was used as the diluent to prepare serial dilutions of the positive sample. Each dilution was tested in duplicate, the mean calculated and the result plotted. The linearity is acceptable if the R-squared value obtained through regression analysis is >=0.90. The results of this study demonstrated that the dilutions recovered were within the acceptance criteria.
Analytical Specificity-Interfering Substances:
The effect of potential interfering substances on sample results generated using the AtheNA Multi-Lyte Borrelia VIsE-1/pepC10 Plus test system was evaluated with the following possible interfering substances at two different concentrations: bilirubin, albumin, cholesterol, triglycerides, hemoglobin and intralipid. The quantity of analyte in each interfering substance is as follows: Bilirubin: 1mg/dL (low), 15 mg/dL (high); Albumin: 3.5 g/dL (low), 5 g/dL (high); Cholesterol: 150 mg/dL (low), 250 mg/dL (high); Triglycerides: 150 mg/dL (low), 500 mg/dL (high); Hemoglobin: 20 g/dL (low), 20 g/dL (high); Intralipid: 300 mg/dL (low), 750 mg/dL (high).
Three samples each for VISE-1 and pepC10 were chosen based on their performance on the AtheNA Multi-Lyte Borrelia VISE-1/pepC10 Plus test system: (strongly reactive and negative and negative). The samples were exposed to the possible interfering substance, tested in duplicate and the mean iAU/mL was determined.
Key Results: All samples showed less than a 20% change in signal in the Vise-1 study with the exception of the borderline VISE-1 sample which exhibited an increase in signal of 32% with the high spike of bilirubin and an increase in signal of 27% with the high spike of cholesterol. The negative VISE-1 sample showed a reduction in signal of 36% with the high spike of hemoglobin, a change in signal of 23% with the low spike of bilirusin and 27% with the high spike of bilirubin, a change in signal of 25% with the low spike of cholesterol and 45% with the high spike of cholesterol and a change in signal of 45% with both the low and high spikes of triglycerides. The change of signal in these negative samples did not change the qualitative outcome, the results remained negative.
All samples showed less than a 20% change in signal in the exception of the exception of the borderline pepC10 sample which exhibited a reduction in signal of 24% with the high spike of hemoglobin and an increase in signal of 28% with the low spike of triglyceride.
Cross Reactivity:
A study was conducted at Zeus Scientific to assess cross reactivity with the AtheNA Multi-Lyte Borrelia VISE-1/pepC10 Plus test system using sera that were sero-positive to EBV VCA IgG, RF, ANA, Syphilis, CMV IgG, CMV IgM, Rubella, VZV IgM and Toxoplasma. ELISA, IFA and micro-particle immunoassay test systems manufactured by various companies for commercial distribution were used to determine the sero-positivity of the samples for each possible cross-reactant were tested.
Key Results: None of the ninety samples showed cross-reactivity with any of the nine analytes tested.
Comparative Data (Clinical Studies)
Study 1. Characterized Samples:
Study Type: Performance with clinical diagnosis (comparison to Predicate ELISA and Western Blot)
N: 229 characterized serum samples
Key Results:
AtheNA Multi-Lyte:
Acute: 21 Pos, 0 Neg/Eqv, Total 21. % agreement with clinical diagnosis: 100% (21/21), 95%CI: 86.7%-100%
Convalescent: 47 Pos, 3 Neg/Eqv, Total 50. % agreement with clinical diagnosis: 94% (47/50), 95%CI: 83.5%-98.8%
Culture (+) early acute: 41 Pos, 38 Neg/Eqv, Total 79. % agreement with clinical diagnosis: 51.9% (41/79), 95%CI: 40.4%-63.3%
Early Convalescent: 62 Pos, 17 Neg/Eqv, Total 79. % agreement with clinical diagnosis: 78.5% (62/79), 95%CI: 67.8%-86.9%
Total: 171 Pos, 58 Neg/Eqv, Total 229. % agreement with clinical diagnosis: 74.7% (171/229), 95%CI: 68.5%-80.2%
Predicate ELISA:
Acute: 21 Pos, 0 Neg/Eqv, Total 21. % agreement with clinical diagnosis: 100% (21/21), 95%CI: 86.7%-100%
Convalescent: 50 Pos, 0 Neg/Eqv, Total 50. % agreement with clinical diagnosis: 100% (50/50), 95%CI: 94.2%-100%
Culture (+) early acute: 37 Pos, 42 Neg/Eqv, Total 78*. % agreement with clinical diagnosis: 47.4% (37/78*), 95%CI: 36.0%-59.1%
Early Convalescent: 73 Pos, 5 Neg/Eqv, Total 78*. % agreement with clinical diagnosis: 93.6% (73/78*), 95%CI: 85.7%-97.9%
Total: 181 Pos, 47 Neg/Eqv, Total 227. % agreement with clinical diagnosis: 79.7% (181/227), 95%CI: 73.9%-84.8%
Western Blot:
Acute: 20 Pos, 1 Neg, Total 21. % agreement with clinical diagnosis: 95.2% (20/21), 95%CI: 76.2%-99.9%
Convalescent: 43 Pos, 7 Neg, Total 50. % agreement with clinical diagnosis: 86% (43/50), 95%CI: 73.3%-95.2%
Culture (+) early acute: 31 Pos, 22 Neg, Total 53*. % agreement with clinical diagnosis: 58.5% (31/53*), 95%CI: 44.1%-71.9%
Early Convalescent: 62 Pos, 13 Neg, Total 75*. % agreement with clinical diagnosis: 82.7% (62/75*), 95%CI: 72.2%-90.4%
Total: 156 Pos, 43 Neg, Total 199. % agreement with clinical diagnosis: 78.4% (156/199), 95%CI: 72.0%-83.9%
Study 2. Prospective Population:
Study Type: Comparison with Predicate ELISA
N: 756 unselected samples
Key Results:
AtheNA Multi-Lyte Vise-1/pepC10 Plus:
Positive: 162 (Predicate ELISA Positive) + 3 (Predicate ELISA Equivocal) + 45 (Predicate ELISA Negative) = 210 Total
Negative: 31 (Predicate ELISA Positive) + 6 (Predicate ELISA Equivocal) + 509 (Predicate ELISA Negative) = 546 Total
Site Total: 193 (Predicate ELISA Positive) + 9 (Predicate ELISA Equivocal) + 554 (Predicate ELISA Negative) = 756 Total
PPA (Positive Percent Agreement): 81.4% (162/199), 95% CI: 75.3-86.6
NPA (Negative Percent Agreement): 91.4% (509/557), 95% CI: 88.7-93.6
Western blot testing was performed on discrepant results. 12/31 samples were negative by blot and 9/31 samples were positive by blot for sera which tested negative on the AtheNA Multi-Lyte test system and positive by ELISA (10/31 samples had no blot data provided). The 3 equivocal samples by the predicate went for second step Western blot testing along with positives. 7/45 samples tested positive and 5/45 samples tested negative by blot for the discrepant samples that were positive on the AtheNA Multi-Lyte.
Study 3. Retrospective Samples:
Study Type: Comparison with Predicate ELISA
N: 242 retrospective samples
Key Results:
AtheNA Multi-Lyte Vise-1/pepC10 Plus:
Positive: 180 (Predicate ELISA Positive) + 7 (Predicate ELISA Equivocal) + 4 (Predicate ELISA Negative) = 191 Total
Negative: 39 (Predicate ELISA Positive) + 6 (Predicate ELISA Equivocal) + 6 (Predicate ELISA Negative) = 51 Total
Site Total: 219 (Predicate ELISA Positive) + 13 (Predicate ELISA Equivocal) + 10 (Predicate ELISA Negative) = 242 Total
PPA AtheNA Multi-Lyte Vise-1/pepC10 Plus: 80% (180/225), 95% CI: 74.2-85.0
NPA AtheNA Multi-Lyte Vise-1/pepC10 Plus for negative results compared to negative/equivocal predicate results: 35.3% (6/17*), 95% CI: 17.3-59.0 (*Statistical significance evaluation cannot be made on limited number of samples.)
Western blot testing was done on discrepant results. 2/37 samples were negative by blot and 37/39 samples were positive by blot for sera which tested negative on the AtheNA Multi-Lyte test system and positive by ELISA. 4/4 samples tested positive by blot for the discrepant samples that were positive on the AtheNA Multi-Lyte test system and negative by ELISA.
Study 4. CDC Characterized Lyme Panel:
Study Type: Comparison with Predicate ELISA and Western Blot
N: 40 samples from CDC
Key Results:
AtheNA Multi-Lyte Borrelia Vise-1/pepC10:
Normals: 0 Pos, 5 Neg, Total 5. % agreement with clinical diagnosis: 100% (5/5)
0-1 month: 3 Pos, 0 Neg, Total 3. % agreement with clinical diagnosis: 100% (3/3)
1-2 months: 5 Pos, 4 Neg, Total 9. % agreement with clinical diagnosis: 55.6% (5/9)
3-12 months: 11 Pos, 5 Neg, Total 16. % agreement with clinical diagnosis: 68.8% (11/16)
12 months: 6 Pos, 1 Neg, Total 7. % agreement with clinical diagnosis: 85.7% (6/7)
Total: 25 Pos, 15 Neg, Total 40. % agreement with clinical diagnosis: 62.5% (25/40)
Predicate ELISA:
Normals: 0 Pos or Eqv, Total 5. % agreement with clinical diagnosis: 100% (5/5)
0-1 month: 3 Pos or Eqv, Total 3. % agreement with clinical diagnosis: 100% (3/3)
1-2 months: 8 Pos or Eqv, Total 9. % agreement with clinical diagnosis: 88.9% (8/9)
3-12 months: 13 Pos or Eqv, Total 16. % agreement with clinical diagnosis: 81.3% (13/16)
12 months: 7 Pos or Eqv, Total 7. % agreement with clinical diagnosis: 100% (7/7)
Total: 31 Pos or Eqv, Total 40. % agreement with clinical diagnosis: 77.5% (31/40)
Western Blot:
Normals: 0 Pos, 5 Neg, Total 5. % agreement with clinical diagnosis: 100% (5/5)
0-1 month: 3 Pos, 0 Neg, Total 3. % agreement with clinical diagnosis: 100% (3/3)
1-2 months: 6 Pos, 3 Neg, Total 9. % agreement with clinical diagnosis: 66.7% (6/9)
3-12 months: 11 Pos, 5 Neg, Total 16. % agreement with clinical diagnosis: 68.8% (11/16)
12 months: 6 Pos, 1 Neg, Total 7. % agreement with clinical diagnosis: 85.7 (6/7)
Total: 26 Pos, 14 Neg, Total 40. % agreement with clinical diagnosis: 65.0% (26/40)
Study 5. Analytical Specificity (Normal Population):
Study Type: Testing of normal population (internal study)
N: 300 samples from New England (endemic), 400 from New Mexico (non-endemic)
Key Results:
Endemic: 262 Negative, 38 Positive. % Positivity: 12.7%
Non-endemic: 361 Negative, 39 Positive. % Positivity: 9.8%
(* % positivity with the predicate was found to be: endemic =14.3%; non-endemic-= 6.5%.)
Precision Studies
Reproducibility:
Assay reproducibility was evaluated at three external clinical sites. Five samples were identified and/or prepared (by Zeus Scientific, Inc.) for use in the study based upon their activity on the AtheNA Multi-Lyte assay. Selected samples were negative, near cut-off, low positive, and moderate and high positive. To assess reproducibility, on each day of testing, each sample was diluted twice and then each dilution was run in triplicate. This was done twice per day by two different technicians, and was repeated for five days.
N: 180 runs for each panel member category (total samples)
Key Results (Total SD and %CV):
VlsE-1 Negative: SD 6.3, %CV 19.7
VlsE-1 Near Cut-off: SD 16.6, %CV 13.5
VlsE-1 Low Positive: SD 16.8, %CV 12.4
VlsE-1 Moderate Positive: SD 49.8, %CV 10.2
VlsE-1 High Positive: SD 112.8, %CV 5.3
pepC10 Negative: SD 3.7, %CV 11.1
pepC10 Near Cut-off: SD 13, %CV 10.4
pepC10 Low Positive: SD 20.3, %CV 10
pepC10 Moderate Positive: SD 124.3, %CV 8.1
pepC10 High Positive: SD 129.3, %CV 6.2
Precision (Repeatability):
Assay repeatability was evaluated at the manufacturer site. Six samples were identified and/or prepared (by Zeus Scientific, Inc.) for use in the study based upon their activity on the AtheNA Multi-Lyte assay. Selected samples were negative, high negative, near cut-off, low positive, and moderate and high positive. On each day of testing, the samples were diluted twice and tested. This was repeated in a second run on the same day by a different technologist for a total of twelve days.
N: 48 runs for each panel member category
Key Results (Total SD and %CV):
VlsE-1 Negative: SD 5.7, %CV 29.7
VIsE-1 high negative: SD 10.5, %CV 11.4
VlsE-1 near cut-off: SD 13.1, %CV 11.0
VlsE-1 low pos: SD 14.4, %CV 11.1
VlsE-1 mod pos: SD 15.1, %CV 9.6
VlsE-1 high pos: SD 139.7, %CV 6.9
pepC10 Negative: SD 5.1, %CV 13.1
pepC10 high neg: SD 11.3, %CV 11.8
pepC10 near cut-off: SD 11.4, %CV 9.5
pepC10 low pos: SD 12.2, %CV 9.4
pepC10 mod pos: SD 41.1, %CV 13.9
pepC10 high pos: SD 65, %CV 5.4
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity (PPA): 81.4% (162/199) for Prospective Population
Specificity (NPA): 91.4% (509/557) for Prospective Population
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.
Zeus Scientific Borrelia burgdorferi ELISA Test System
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).
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Image /page/0/Picture/0 description: The image shows the text "K100728" at the top, followed by "JUL -6 2010" on the left side. There is a number "1" at the bottom. The text appears to be handwritten or printed with a slightly rough or uneven quality.
Zeus Scientific Inc. 510(k) AtheNA Multi-Lyte Borrelia VlsE-1/ pepC10 Plus Test System Summary of Safety and Effectiveness
Section I: Administrative Information
- Submission Purpose: Intent to market referenced device for the qualitative detection of VlsE-1 1. and pepC10 antibodies.
- Measurand: VIsE-1 IgG and pepC10 IgM antibodies. 2.
- Type of Test: Sandwich Immunoassay. 3.
- Applicant: Zeus Scientific, Inc. , PO Box 38, Raritan, NJ 08869 (908)526-3744 4.
- Establishment Registration Number: 2242426 5.
- Contact: Ewa Nadolczak, Manager of Clinical Affairs (347)731-0402 6. enadolczak@zeusscientific.com
- Proprietary Name: AtheNA Multi-Lyte® Borrelia VlsE-1/ pepC10 Plus Test System. 7.
- Established name: Borrelia serological reagents. 8.
Section 2: Regulatory Information
- Device Classification: Borrelia Serological Reagent 1.
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- Class: Class 2
- Product Code: LSR 3.
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- Panel Microbiology
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- Form 3454: Appendix A
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- Device Hazard Analysis: Appendix B
Section 3: Intended Use
The Zeus Scientific, Inc AtheNA Multi-Lyte Borrelia VISE-1/ pepC10 Plus Test System is a multiplexed sandwich immunoassay for the qualitative detection of IgG class antibody to recombinant VISE-1 and the IgM class of antibody to synthetic pepC10 in human serum. The AtheNA Multi-lyte Borrelia VISE-1/pepC10 Plus Test System is intended for use with the Luminex® 200 IS and the AtheNA Multi-Lyte data management package in testing serum samples from symptomatic patients or those with a history of Lyme Borreliosis. All positive specimens should be tested with a second-tier test such as Western Blot which if positive, is supportive evidence of infection with B.burgdorferi. Diagnosis of Borreliosis should be made based on the presence of 8.burgdorferi antibodies, history, symptoms and other laboratory data. Negative first or second tier results should not be used to exclude Borreliosis.
1
Section 3A: Special Conditions for Use
The AtheNA Multi-Lyte Borrelia VlsE-1/ pepC10 Plus Test System is for in vitro diagnostic use only.
The AtheNA Multi-Lyte Borrelia VlsE-1/ pepC10 Plus Test System is for prescription use only.
Section 4: Device Description
The AtheNA Multi-Lyte Borrelia VlsE-1/pepC10 Plus Test System is a micro particle immunoassay intended for the qualitative detection of distinct IgG class antibody to VlsE-1 and distinct IgM antibody to pepC10. The assay is a multiplexed immunoassay designed to simultaneously detect, distinguish and identify IgG reactivity to recombinant VISE-1 antigen and IgM reactivity to synthetic pepC10 antigen. The test system is comprised of the AtheNA Multi-Lyte test kit and the Luminex Corp instrument model number Luminex™ 200 IS and software version 3.
The AtheNA Multi-Lyte Borrelia VIsE-1/pepC10 Plus test system provides the following Components:
Reactive Reagents:
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- All reactive reagents contain sodium azide as a preservative at a concentration of 0.1% (w/v).
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- Multiplexed bead suspension 1. Ready to use, 5.5 mL bottle. The suspension contains separate distinguishable 5.6 micron polystyrene beads that are conjugated with recombinant VlsE1 antigen. The bead mix also contains one bead set designed to detect non-specific antibodies in the patient sample (if present) and four separate bead sets used for assay calibration.
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- Multiplexed bead suspension 2. Ready to use, 5.5 mL bottle. The suspension contains separate distinguishable 5.6 micron polystyrene beads that are conjugated with the following antigens: recombinant VlsE-1 and synthetic pepC10.
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- Conjugate 1: Phycoerythrin conjugated goat anti-human IgG (y chain specific). Ready to use, 15 mL amber bottle.
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- Conjugate 2: Phycoervthrin conjugated goat anti-human IgM (μ chain specific). Ready to use, 15 mL amber bottle.
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- Human positive serum controls. Two, 0.2 mL vials.
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- Human negative serum control. One, 0.2 mL vial.
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- SAVe Diluent®. One 50 mL bottle containing phosphate-buffered-saline. Ready to use. NOTE: the sample diluent will change color in the presence of serum.
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- Wash Buffer Concentrate: dilute 1 part concentrate + 9 parts deionized or distilled water. One bottle containing 10 X concentrate of phosphate buffered saline.
Non-Reactive Reagents:
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- One, dilution plate
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- One, 96-well filtration plate for rinsing the microspheres
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- Data Labels: One label is adhered to the inside lid of the kit box and a second label is inside the kit box.
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- Package Insert providing instructions for use
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- Calibration CD: a compact disc that includes all lot-specific kit calibration values required for specimen analysis and assay quality control
2
Instrument and Software
This assay is platform dependant and used in conjunction with the Luminex 100 IS and the AtheNA Multi-Lyte® Test System Data Analysis Package Version 3.0.
Materials required but not provided:
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- AtheNA Multi-Lyte® System (Luminex® instrument)
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- Pipettes capable of accurately delivering 10 to 200 µL
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- Multichannel pipette capable of accurately delivering (10 to 200 µL)
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- Reagent reservoirs for multichannel pipettes
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- Disposable pipette tips
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- Laboratory timer to monitor incubation steps
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- Small bath sonicator
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- Plate shaker capable of shaking at 800 RPM (optional for mixing)
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- Vacuum aspirator and vacuum manifold for washing the microspheres
Section 5: Substantial Equivalence
Examination of enclosed data indicates that the Zeus Scientific, Inc AtheNA Multi-Lyte Borrelia VISE-1/pepC1- Plus Test System for the detection of IgG class antibody to VisE-1 and IgM antibody to pepC10 is substantially equivalent to a commercially marketed test system which has been previously cleared by the FDA for in vitro diagnostic use.
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- Name of Predicate Device: Zeus Scientific Borrelia burgdorferi ELISA Test System
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- Manufacturer of Predicate Device: Zeus Scientific, Inc.
- Methodology of Predicate: enzyme-linked immunosorbent assay 3.
Section 5A: Interpretation of Results
Investigational Device: AtheNA Score: raw fluorescence is converted into intermediate AtheNA Unit values (iAU/mL). These values correspond to the amount of human IgM antibody bound to the VISE-1 and/or pepC10 antigen coated beads respectively. iAU/mL values are converted to a single outcome (AtheNA Score).
Investigational Device: AtheNA Scores Negative: Borrelia burgdorferi in human serum. This test system should only be used with patients with signs and symptoms that are consistent with Lyme disease. Equivocal or positive results must be supplemented by testing with a standardized Western Blot procedure. Positive supplemental results are supportive evidence of exposure to B. burgdorferi and can be used to support a clinical diagnosis of Lyme disease. |
| Intended Use | | |
| Assay | Immunoassay | Immunoassay |
| Detection Method | Fluorescent | Colorimetric |
| Solid Phase | Polystyrene micro particle | Polystyrene micro wells |
| Antigen Used | Recombinant VIsE-1 antigen and synthetic pepC10 antigen | Inactive Borrelia burgdorferi (B31 Strain) |
| Specimen Tested | Human Serum | Human Serum |
| Controls | Two PC and one NC | One PC and one NC |
| Calibration | Includes Intra-Well Calibration® that provides a separate calibration curve for every sample
Human IgG and IgM | One calibrator |
| Analyte Measured | | Human IgG and IgM |
| Sample Dilution | 1:21 in SAVe Diluent | 1:21 in SAVe Diluent |
| Sample Incubation | 30 +/- 10 minutes at room temperature | 25 +/- 5 minutes at room temperature |
| Post Sample Wash | 3x wash (vacuum filtration) | 5X wash (manual or automated) |
| Conjugate | Goat anti-human IgG; y chain specific Goat anti-human IgM; u chain specific | Goat anti-human IgM/IgG |
| Conjugate Label | Phycoerythrin | horseradish peroxidase |
| Conjugate Incubation | 30 +/- 10 minutes at room temperature | 25 +/- 5 minutes at room temperature |
| Post Conjugate Wash | N/A | 5X wash (manual or automated) |
| Substrate | N/A | TMB |
| Reading | Read the fluorescence on the beads | Read the optical density against the blank |
| Data Points | Read a minimum of 50 beads (events) for each bead in the bead mix. | Read one OD value for each control and sample |
| Math | Multi-point curve, regression analysis | Single point regression |
| Scale | Intra-Well Calibration determines a unit value for each sample from the regression curve. Unit values for each analyte are converted to a single AtheNA Score.
Negative is 12 months | 6 | 1 | 7 | 85.7% (6/7) | 7 | 0 | 7 | 100% (7/7) | 6 | 1 | 7 | 85.7 (6/7) |
| Total | 25 | 15 | 40 | 62.5% (25/40) | 31 | 9 | 40 | 77.5% (31/40) | 26 | 14 | 40 | 65.0% (26/40) |
Analytical Specificity
Study 5. Analytical Specificity: Testing of normal population was done on 300 samples acquired from blood donors in the New England endemic area and 400 samples acquired from blood donors and individuals undergoing routine testing not infectious in nature in the New Mexico non-endemic area.
Table 5. Analytical Specificity.
| Sample Type | Volume | Negative | Positive | % Positivity |
|---|---|---|---|---|
| Endemic | 300 | 262 | 38 | 12.7% |
| Non-endemic | 400 | 361 | 39 | 9.8% |
- % positivity with the predicate was found to be: endemic =14.3%; non-endemic-= 6.5%.
Section 9A: Precision Studies
Reproducibility
Assay reproducibility was evaluated at three external clinical sites. The study was conducted as follows: Five samples were identified and/or prepared (by Zeus Scientific, Inc.) for use in the study based upon their activity on the AtheNA Multi-Lyte assay. Selected samples were negative, near cut-off, low positive, and moderate and high positive. To assess reproducibility, on each day of testing, each sample was diluted twice and then each dilution was run in triplicate. This was done twice per day by two different technicians, and was repeated for five days.
| Panel
Member | Sample
N | Mean
AU/mL | Within-Run | | Within-Day | | Between-Run | | Between-Site | | Total | |
|--------------------------|-------------|---------------|------------|------|------------|------|-------------|------|--------------|------|-------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| VlsE-1 Negative | 180 | 31 | 4.5 | 14.7 | 5.5 | 17.9 | 3.7 | 12.1 | 5.9 | 18.8 | 6.3 | 19.7 |
| VlsE-1 Near Cut-off | 180 | 110.4 | 12.8 | 11.6 | 14 | 12.6 | 7.5 | 6.7 | 15.2 | 13.3 | 16.6 | 13.5 |
| VlsE-1 Low Positive | 180 | 136.7 | 13.8 | 20.2 | 15.6 | 11.4 | 9.1 | 6.7 | 16.8 | 11.5 | 16.8 | 12.4 |
| VlsE-1 Moderate Positive | 180 | 312.7 | 24.5 | 7.7 | 32.7 | 10.2 | 26.5 | 8.2 | 43.4 | 9.7 | 49.8 | 10.2 |
| VlsE-1 High Positive | 180 | 1869 | 103.1 | 5.5 | 105.6 | 5.6 | 37.5 | 2 | 107.6 | 5.4 | 112.8 | 5.3 |
| pepC10 Negative | 180 | 23.6 | 1.9 | 7.8 | 2.3 | 9.8 | 7.5 | 6.4 | 3.4 | 10.2 | 3.7 | 11.1 |
| pepC10 Near Cut-off | 180 | 108.9 | 10 | 9 | 11 | 10 | 5.4 | 4.9 | 13 | 10.3 | 13 | 10.4 |
| pepC10 Low Positive | 180 | 150.8 | 10.5 | 6.9 | 15.2 | 9.9 | 12.7 | 8.1 | 17.9 | 9.5 | 20.3 | 10 |
Table 6. Summary Of Reproducibility
12
| pepC10 Moderate Positive | 180 | 192.3 | 12.8 | 6.8 | 15.6 | 8.1 | 10.7 | 5.5 | 23 | 8 | 124.3 | 8.1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| pepC10 High Positive | 180 | 1222.0 | 58.1 | 4.7 | 70.8 | 5.7 | 49 | 3.8 | 93.4 | 5.9 | 129.3 | 6.2 |
Precision
Assay repeatability was evaluated at the manufacturer site. The study was conducted as follows: six samples were identified and/or prepared (by Zeus Scientific, Inc.) for use in the study based upon their activity on the AtheNA Multi-Lyte assay. Selected samples were negative, high negative, near cut-off, low positive, and moderate and high positive. On each day of testing, the samples were diluted twice and tested. This was repeated in a second run on the same day by a different technologist for a total of twelve days. This study is summarized in iAU to assess detailed individual bead performance.
Table 7. Summary of Repeatability
| Panel
Member | Sample
N | Mean
AU/mL | Within Run | | Within Day | | Total | |
|----------------------|-------------|---------------|------------|------|------------|------|-------|------|
| | | | SD | %CV | SD | %CV | SD | %CV |
| VIsE-1Negative 1 | 48 | 37.9 | 4.5 | 11.4 | 9.2 | 25.1 | 5.7 | 29.7 |
| VISE-1 high negative | 48 | 91.7 | 6.4 | 7.1 | 7.1 | 7.7 | 10.5 | 11.4 |
| near cut-off | 48 | 119.6 | 8.1 | 6.6 | 9.9 | 8.3 | 13.1 | 11.0 |
| low pos | 48 | 129.8 | 8.2 | 6.4 | 11.6 | 9.0 | 14.4 | 11.1 |
| mod pos | 48 | 157.3 | 11.3 | 7 | 11.1 | 6.9 | 15.1 | 9.6 |
| high pos | 48 | 2031 | 111.1 | 5.4 | 119.8 | 5.9 | 139.7 | 6.9 |
| pepC10 Negative 1 | 48 | 36.8 | 3.9 | 10.5 | 4.1 | 11.0 | 5.1 | 13.1 |
| pepC10high neg | 48 | 95.2 | 6.3 | 6.3 | 8.9 | 9.4 | 11.3 | 11.8 |
| pepC10 near cut-off | 48 | 119.4 | 7.4 | 6.1 | 7.9 | 6.6 | 11.4 | 9.5 |
| pepC10 low pos | 48 | 130.4 | 9.7 | 7.4 | 10.5 | 8.0 | 12.2 | 9.4 |
| pepC10 mod pos | 48 | 295.4 | 28.4 | 9.5 | 34.0 | 11.5 | 41.1 | 13.9 |
| pepC10 high pos | 48 | 1207.2 | 38.4 | 3.2 | 52.8 | 4.4 | 65 | 5.4 |
13
Image /page/13/Picture/1 description: The image shows the address for the Food and Drug Administration. The address is 10903 New Hampshire Avenue, Document Mail Center - WO66-0609, Silver Spring, MD 20993-0002. The text is left-aligned and uses a serif font.
Zeus Scientific, Inc. C/O Ewa K. Nadolczak Manager, Clinical Affairs P.O. Box 38 Raritan, NJ 08869
JUL 0 6 2019
Re: K100728
Trade/Device Name: AtheNA Multi-Lyte Borrelia VIsE-1/pepC10 Plus Test System Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema pallidum treponemal test reagents Regulatory Class: Class II Product Code: LSR Dated: March 10, 2010 Received: April 9, 2010
Dear Ms. Nadolczak:
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 class II (Special Controls), 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); medical device reporting (reporting of
14
Page 2-Ewa K. Nadolczak
medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 the CDRH's Office
of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Sally Hojvat, M.Sc., h.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
15
Indications for Use
2 100 728 510(k) Number (if known): Device Name: AtheNA Multi-Lyte® Borrelia VLSe-1/pepC10 Plus Test System
Indications for Use:
The Zeus Scientific, Inc AtheNA Multi-Lyte Borrelia VisE-1/ pepC10 Plus Test System is a multiplexed sandwich immunoassay for the qualitative detection of IgG class antibody to recombinant VlsE-1 and the IgM class of antibody to synthetic pepC10 in human serum. The AtheNA Multi-lyte Borrelia VlsE-1/pepC10 Plus Test System is intended for use with the Luminex® 200 IS and the AtheNA Multi-Lyte data management package in testing serum samples from symptomatic patients or those with a history of Lyme Borreliosis. All positive specimens should be tested with a second-tier test such as Western Blot which if positive, is supportive evidence of infection with B.burgdorferi. Diagnosis of Borreliosis should be made based on the presence of B.burgdorferi antibodies, history, symptoms and other laboratory data. Negative first or second tier results should not be used to exclude Borreliosis. This kit is for in vitro diagnostic use only.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off
ice of In Vitro Diagnostic Device aluation and Safety
Page 1 of -
510(k) k 100728