(92 days)
The Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test Kit is intended as a qualitative presumptive (first-step) test for the detection of IgG and IgM antibodies to B. burgdorferi sensu stricto in human serum from symptomatic patients or people suspected of infection. Positive and equivocal results must be supplemented by testing with a second-step Western blot assay.
The kit includes 12 x 8 well Antigen Coated strips, Conjugate, Substrate, Stop Solution, Wash Buffer. Diluent. Negative Control. Positive Control. The control. The controls are provided to determine if the assay is functioning properly and to determine the antibody level. The reagents are sufficient for 96 determinations.
During the test procedure, antibodies to B. burgdorferi (sensu stricto) if present in the human serum sample will bind to the antigens coated onto the wells forming antigen-antibody complexes. Excess antibodies are removed by washing. A conjugate of goat anti-human IgG/IgM antibodies conjugated with horseradish peroxidase are then added, which binds to the antigen-antibody complexes. Excess conjugate is removed by washing. This is followed by the addition of a chromogenic substrate, tetramethylbenzidine (TMB). If specific antibodies to the antigen are present in the patients' serum, a blue color will develop. The enzymatic reaction is then stopped with a stopping solution causing the contents of the well to turn yellow. The wells are read photometrically with a microplate reader at 450nm.
The antigens used in the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test kit is a combination of B. burgdorferi sensu strain B31 lysate, B. burgdorferi sensu stricto strain 2591 lysate, and a recombinant VIsE from B. burgdorferi sensu stricto strain B31. The lysates use spirochetes growing in BSK-H complete medium until mid-exponential phase. The recombinant VlsE protein is produced in E. coli SURE2 cells and purified by affinity chromatography. The purity of each antigen is assayed by SDS-PAGE followed by Coomassie staining and/or Western blotting.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct numerical targets in the provided document. Instead, the document demonstrates substantial equivalence to a predicate device and provides performance metrics from various studies. Based on the studies performed, the "reported device performance" is presented in the context of sensitivity, specificity, agreement with the predicate device, precision, and reproducibility.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Analytical Specificity (Non-endemic region) | 98.0% (2 cases positive/equivocal out of 100 samples) |
| Analytical Specificity (Endemic region) | 97.3% (3 cases positive/equivocal out of 110 samples) |
| Precision (Within-Run CV) | Moderate Positive: 4.2%; Low Positive: 2.2%; High Negative: 3.4%; Negative: 6.6% |
| Precision (Total CV) | Moderate Positive: 8.9%; Low Positive: 11.9%; High Negative: 11.4%; Negative: 11.6% |
| Reproducibility (Within-Run CV) | Moderate Positive: 5.3%; Low Positive: 4.3%; High Negative: 5.0%; Negative: 9.1% |
| Reproducibility (Total CV) | Moderate Positive: 9.0%; Low Positive: 9.4%; High Negative: 12.8%; Negative: 23.0% |
| Cross-Reactivity (Demonstrated absence of significant interference from listed conditions) | Low false positive rates observed for conditions like Tick-borne Relapsing Fever (7.7%), Treponemal Infections (8.7%), Fibromyalgia (10%); 0% for Rickettsia, Ehrlichiosis, Babesiosis, Leptospirosis, Parvovirus B19, Influenza A&B, Epstein-Barr Virus, Cytomegalovirus, H. pylori, Rheumatoid Arthritis, Herpes Simplex Virus, Varicella Zoster Virus, Autoimmune Disease. (Note: 2 Treponemal Infection samples were also positive on the predicate device). |
| Interfering Substances (Demonstrated no effect) | None detected for Albumin, Bilirubin, Cholesterol, Hemoglobin, Triglycerides at specified concentrations. |
| Positive Percent Agreement with Predicate Device | 96.0% (72/75), 95% CI (88.8% - 99.2%) |
| Negative Percent Agreement with Predicate Device | 97.5% (434/445), 95% CI (95.6% - 98.8%) |
| Clinical Sensitivity (Overall from Sensitivity Study) | Early: 76.3%; Disseminated: 100.0%; Late: 97.2% |
| Clinical Sensitivity (CDC Panel) | Healthy: 100%; Early (0-2m): 86.7%; Convalescent (3-12m): 53.8%; Late (>1yr): 100% |
| Equivalence to Predicate Device | Demonstrated substantial equivalence through comparative performance in clinical and analytical studies. |
2. Sample Sizes and Data Provenance
- Test Set (Clinical Studies):
- Comparison with Predicate Device: 520 serum samples (prospective samples).
- Sensitivity Study (Clinically Characterized): 89 clinically characterized samples.
- CDC Panel: 40 samples (5 healthy, 35 Lyme disease stratified by stage).
- Analytical Specificity: 210 asymptomatic individuals (110 from endemic region/Pennsylvania, 100 from non-endemic region/Arizona).
- Cross-Reactivity: 221 samples (obtained from serum vendors, confirmed positive for respective markers).
- Interfering Substances: 3 samples (negative, low positive, moderate positive, spiked).
- Data Provenance: The data appears to be from a mix of regions within the US (Pennsylvania, Arizona for specificity, CDC for panel), and some samples from "serum vendors" for cross-reactivity. The clinical comparison study used "prospective samples submitted for Lyme serology testing" from three sites (one internal, two external reference laboratories). The sensitivity study used "clinically characterized samples."
3. Number of Experts and Qualifications for Ground Truth (Test Set)
- The document does not specify the number or qualifications of experts used to establish ground truth for the test set in the comparative clinical studies or sensitivity studies.
- For the "clinically characterized samples" and "patients diagnosed with Lyme disease" (CDC panel), it is implied that a clinical diagnosis (made by medical professionals) served as the ground truth, but no details on the specific experts (e.g., infectious disease specialists, their experience) are provided.
- For cross-reactivity, samples were from "serum vendors who confirmed their positivity for each respective marker," which likely relied on established diagnostic methods but doesn't detail expert involvement.
4. Adjudication Method (Test Set)
- The document does not describe a specific adjudication method (e.g., 2+1, 3+1, none) for resolving discrepancies in the test set.
- For the "Comparison with Predicate Device" table, "Equivocal samples counted as positive" is an interpretation rule, not an adjudication method for ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) ELISA test kit, which is a laboratory assay and does not involve human readers interpreting results in the same way an imaging AI would. Therefore, the concept of human readers improving with AI assistance is not applicable here.
6. Standalone Performance (Algorithm Only)
- Yes, the performance presented for the "Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test Kit" throughout the document (e.g., Precision, Reproducibility, Analytical Specificity, Cross-Reactivity, and its results in the Clinical Sensitivity and CDC Panel studies) is its standalone performance. This test kit is a self-contained diagnostic assay.
7. Type of Ground Truth Used
- Clinical Diagnosis/Characterization: For the sensitivity study and the CDC panel, the ground truth was based on "clinically characterized samples" and "patients diagnosed with Lyme disease," implying a clinical diagnosis by medical professionals.
- Absence of Disease/Asymptomatic Status: For the analytical specificity study, ground truth was derived from "asymptomatic individuals" from endemic and non-endemic regions, presumed to be negative for Lyme disease.
- Confirmed Positivity: For the cross-reactivity study, samples were from "serum vendors who confirmed their positivity for each respective marker."
- ELISA Results (Predicate Device): For the "Comparison with Predicate Device" study, the predicate device's results served as a comparative reference point, but not necessarily the ultimate gold standard for true disease status.
8. Sample Size for the Training Set
- The document implicitly references a "training set" for the establishment of the assay cutoff: "The cutoff was determined by testing a total of 200 normal sera which consisted of 100 sera from an endemic region of Lyme disease and 100 sera from a non-endemic region of Lyme disease."
- Additionally, after initial cutoff determination, "125 characterized Lyme disease samples were tested" and an ROC analysis was generated with the 325 samples (200 normal and 125 characterized samples) "to verify the chosen cutoff." This combined set of 325 samples served as a "training" or calibration set for optimizing the assay's cutoff.
9. How the Ground Truth for the Training Set was Established
- For the "training set" used to determine the assay cutoff:
- Normal Sera: The 200 normal sera were obtained from "an endemic region of Lyme disease and a non-endemic region of Lyme disease." Their "normal" status implies they were considered negative for Lyme disease based on clinical assessment or lack of symptoms/exposure.
- Characterized Lyme Disease Samples: The 125 "characterized Lyme disease samples" likely had a confirmed clinical diagnosis of Lyme disease, although specific details of this characterization are not provided. The phrase "characterized Lyme disease samples" implies a definitive diagnosis beyond just a positive test.
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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 is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
May 2, 2018
Gold Standard Diagnostics Napoleon Monce Director, Product Development 2851 Spafford St. Davis, California 95618
Re: K180264
Trade/Device Name: Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test Kit Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema pallidum treponemal test reagents Regulatory Class: Class II Product Code: LSR Dated: January 26, 2018 Received: January 30, 2018
Dear Napoleon Monce:
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. 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 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
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Part 820); 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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,
Steven R. Gitterman -S
for
Uwe Scherf, M.Sc., 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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Indications for Use
510(k) Number (if known) K180264
Device Name
Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test Kit
Indications for Use (Describe)
The Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test Kit is intended as a qualitative presumptive (first-step) test for the detection of IgG and IgM antibodies to B. burgdorferi sensu stricto in human serum from symptomatic patients or people suspected of infection. Positive and equivocal results must be supplemented by testing with a second-step Western blot assay.
| 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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Image /page/3/Picture/0 description: The image is a logo for Gold Standard Diagnostics. The logo features the words "GOLD STANDARD" in large, bold, black letters. The word "GSD" is inside of a golden globe to the left of the word "GOLD". Below the words "GOLD STANDARD" is the word "DIAGNOSTICS" in smaller, black letters.
510(k) Summary
This 510(k) summary is being submitted in accordance with the requirement of SMDA 1990 and 21 CFR 807.92.
-
- Submitter's Name: Gold Standard Diagnostics Address: 2851 Spafford St. Davis, CA. 95618 Phone Number: 530-759-8000 Contact Person: Napoleon Monce January 26, 2018 Date:
-
- Product and Trade Name: Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test Kit
Common Name: Lyme ELISA Test
Regulation Section: (21 CFR 866.3830) Treponema pallidum treponemal test reagents.
Classification: Class II
Product Code: LSR; Reagent, Borrelia Serological Reagent
-
- Legally Marketed Device to Which the Submitter Claims Equivalence:
Trinity Biotech Captia™ Borrelia burgdorferi IgG/IgM ELISA Test Kit (K033070).
- Legally Marketed Device to Which the Submitter Claims Equivalence:
4) Description of the Device:
The kit includes 12 x 8 well Antigen Coated strips, Conjugate, Substrate, Stop Solution, Wash Buffer. Diluent. Negative Control. Positive Control. The control. The controls are provided to determine if the assay is functioning properly and to determine the antibody level. The reagents are sufficient for 96 determinations.
During the test procedure, antibodies to B. burgdorferi (sensu stricto) if present in the human serum sample will bind to the antigens coated onto the wells forming antigen-antibody complexes. Excess antibodies are removed by washing. A conjugate of goat anti-human IgG/IgM antibodies conjugated with horseradish peroxidase are then added, which binds to the antigen-antibody complexes. Excess conjugate is removed by washing. This is followed by the addition of a chromogenic substrate, tetramethylbenzidine (TMB). If specific antibodies to the antigen are present in the patients' serum, a blue color will develop. The enzymatic reaction is then stopped with a stopping solution causing the contents of the well to turn yellow. The wells are read photometrically with a microplate reader at 450nm.
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The antigens used in the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test kit is a combination of B. burgdorferi sensu strain B31 lysate, B. burgdorferi sensu stricto strain 2591 lysate, and a recombinant VIsE from B. burgdorferi sensu stricto strain B31. The lysates use spirochetes growing in BSK-H complete medium until mid-exponential phase. The recombinant VlsE protein is produced in E. coli SURE2 cells and purified by affinity chromatography. The purity of each antigen is assayed by SDS-PAGE followed by Coomassie staining and/or Western blotting.
5) Intended Use of the Device:
The Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test kit is intended as a qualitative presumptive (first step) test for the detection of IgG and IgM antibodies to B. burgdorferi sensu stricto in human serum from symptomatic patient or people suspected of infection. Positive and equivocal results must be supplemented by testing with a second-step Western blot assay.
6) Comparison with the Predicate Device:
The tables below provide a comparison of the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test kit with the Trinity Biotech Captia™ Borrelia burgdorferi IgG/IgM ELISA Test kit (predicate device: K033070).
| Similarities | ||
|---|---|---|
| Item | Subject Device: Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test Kit | Predicate Device: Trinity Biotech Captia™ Borrelia burgdorferi IgG/IgM ELISA Test Kit |
| Intended Use | The Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test kit is intended as a qualitative presumptive (first step) test for the detection of IgG and IgM antibodies to B. burgdorferi sensu stricto in human serum from symptomatic patients or people suspected of infection. Positive and equivocal results must be supplemented by testing with a second-step Western blot assay. | Trinity Biotech Captia™ Borrelia burgdorferi IgG/IgM ELISA Test kit is intended for the qualitative presumptive (first-step) detection of total (IgG/IgM) antibodies to B. burgdorferi in human serum. This ELISA should only be used for 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 (second step) procedure. Positive supplemental (second-step) results are supportive evidence of exposure to B. burgdorferi and can be used to support a clinical diagnosis of Lyme disease. 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. |
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| burgdorferi. Negative results(either first or second step) shouldnot be used to exclude Lymedisease. | ||
|---|---|---|
| Assay Format | Antigen coated microtiter plate – 96wells. | Same |
| Technology | ELISA | Same |
| Sample Matrix | Human serum | Same |
| Controls Provided | Positive, Cutoff, Negative | Same |
| Reagents Provided | Diluent, Wash, Conjugate, Substrate,Stop Solution | Same |
| Reported Results | Positive, Equivocal, Negative | Same |
| Interpretation | Optical density readings fromSpectrophotometer | Same |
| Differences | ||
|---|---|---|
| Item | Subject Device: Gold StandardDiagnostics Borrelia burgdorferiIgG/IgM ELISA Test Kit | Predicate Device: Trinity BiotechCaptia™ Borrelia burgdorferiIgG/IgM ELISA Test Kit |
| Sample Processing | Dilute Samples 1:100 in Diluent | Dilute Samples 1:20 in Diluent |
| Volumes | 100ul sample, 50ul substrate, 50ulstop solution | 100ul sample, 100ul substrate,100ul stop solution |
| Incubation | 15/15/15 minutes at roomtemperature | 25/25/10-15 minutes at roomtemperature |
| Antigens | B. burgdorferi B31 strain,B. burgdorferi 2591 strain,B. burgdorferi recombinant VlsEB31 strain | B. burgdorferi B31 strain |
| Results Interpretation | Convert to units.Negative <9Equivocal 9.0-11.0Positive >11.0 | Convert to units.Negative ≤0.90Equivocal 0.91-1.09Positive ≥1.10 |
6(b1): Nonclinical Studies:
Determination of the Assay Cutoff
The cutoff was determined by testing a total of 200 normal sera which consisted of 100 sera from an endemic region of Lyme disease and 100 sera from a non-endemic region of Lyme disease. The mean plus two standard deviations was used to determine the assay cutoff. A known positive sample was then diluted to produce a ready to use cutoff control. After the cutoff was determined 125 characterized Lyme disease samples were tested. An ROC analysis was then generated with the 325 samples (200 normal and 125 characterized samples) to verify the chosen cutoff. The analysis confirmed that the assay cutoff provided an optimal level of sensitivity and specificity.
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Precision
To determine the precision of the Borrelia burgdorferi IgG/IgM ELISA Test, a within-lab precision study was conducted. A precision panel consisting of a negative sample, a high negative sample, a low positive sample, and a moderate positive sample, along with the kit controls, was tested in-house. The sample panel was masked and randomized. Each of the panel members was tested in duplicate, twice per day, for 12 days. The sample panel was masked and randomized. The results are summarized in the following table:
| Sample | N | MeanUnits | Within-Run | Between-Run | Between-Day | Total | |
|---|---|---|---|---|---|---|---|
| ModeratePositive | 48 | 19.6 | SD | 0.815 | 1.534 | 1.472 | 1.737 |
| CV | 4.2% | 7.8% | 7.5% | 8.9% | |||
| LowPositive | 48 | 12.1 | SD | 0.267 | 1.417 | 1.248 | 1.442 |
| CV | 2.2% | 11.7% | 10.3% | 11.9% | |||
| HighNegative | 48 | 6.1 | SD | 0.211 | 0.662 | 0.642 | 0.695 |
| CV | 3.4% | 10.8% | 10.5% | 11.4% | |||
| Negative | 48 | 1.7 | SD | 0.113 | 0.164 | 0.151 | 0.199 |
| CV | 6.6% | 9.6% | 8.8% | 11.6% |
Reproducibility
A reproducibility panel consisting of a negative sample, a high negative sample, a low positive sample, and a moderate positive sample, along with the kit controls, was tested at three different sites. The sample panel was masked and randomized. Each of the panel members was tested in triplicate, twice per day, for five days. The Within-Run, Between-Days, and Between-Sites Standard Deviation and Coefficients of Variation (CV) were calculated. The sample panel was masked and randomized. The results are summarized in the following table:
| Sample | N | MeanUnits | Within-Run | Between-Run | Between-Day | Between-Sites | Total | |
|---|---|---|---|---|---|---|---|---|
| ModeratePositive | 90 | 21.1 | SD | 1.117 | 1.543 | 1.434 | 0.386 | 1.905 |
| CV | 5.3% | 7.3% | 6.8% | 1.8% | 9.0% | |||
| LowPositive | 90 | 13.8 | SD | 0.591 | 1.155 | 1.026 | 0.404 | 1.297 |
| CV | 4.3% | 8.4% | 7.5% | 2.9% | 9.4% | |||
| HighNegative | 90 | 6.4 | SD | 0.323 | 0.756 | 0.715 | 0.237 | 0.822 |
| CV | 5.0% | 11.7% | 11.1% | 3.7% | 12.8% | |||
| Negative | 90 | 1.6 | SD | 0.145 | 0.335 | 0.312 | 0.347 | 0.365 |
| CV | 9.1% | 21.1% | 19.6% | 21.8% | 23.0% |
Analytical Specificity
The analytical specificity was determined by testing 210 asymptomatic individuals' samples from endemic (Pennsylvania) and non-endemic (Arizona) regions. The Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test results are summarized in the following table:
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| Number of Samples | NumberPositive/Equivocal | Analytical Specificity | |
|---|---|---|---|
| Endemic Region | 110 | 3 | 97.3% |
| Non-endemic Region | 100 | 2 | 98.0% |
Cross Reactivity
A study using 221 samples was conducted to evaluate potential cross reactivity from different disease conditions. The samples were obtained from serum vendors who confirmed their positivity for each respective marker. The samples were tested on the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test. The results are summarized in the following table:
| Infection / Diagnosis | Number of SeraTested | # Positive / (%) |
|---|---|---|
| Tick-borne Relapsing Fever | 26 | 2 / (7.7%) |
| Treponemal Infections | 23 | 2* (8.7%) |
| Rickettsia | 10 | 0 / (0%) |
| Ehrlichiosis | 10 | 0 / (0%) |
| Babesiosis | 11 | 0 / (0%) |
| Leptospirosis | 11 | 0 / (0%) |
| Parvovirus B19 | 12 | 0 / (0%) |
| Influenza A&B | 10 | 0 / (0%) |
| Epstein-Barr Virus | 10 | 0 / (0%) |
| Cytomegalovirus | 19 | 0 / (0%) |
| H. pylori | 11 | 0 / (0%) |
| Fibromyalgia | 10 | 1/ (10%) |
| Rheumatoid Arthritis | 11 | 0 / (0%) |
| Herpes Simplex Virus | 13 | 0 / (0%) |
| Varicella Zoster Virus | 12 | 0 / (0%) |
| Autoimmune Disease | 22 | 0 / (0%) |
*Also positive on the predicate device
Interfering Substances
The effect of potential interfering substances on samples using the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test was evaluated. Three samples, a negative, a low positive and a moderate positive were spiked with high levels of interferants and were tested along with serum without spiked interferants. The recommended concentrations from the guideline "Interference Testing in Clinical Chemistry EP7-A2" from the Clinical and Laboratory Standards Institute were used (see table below). The tested substances did not affect the performance of the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELIS A Test.
| Substance | Concentration | Interference |
|---|---|---|
| Albumin | 120 g/L | None detected |
| Bilirubin | 342 umol/L | None detected |
| Cholesterol | 13 mmol/L | None detected |
| Hemoglobin | 2 g/L | None detected |
| Triglycerides | 37 mmol/L | None detected |
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6(b2): Clinical Studies:
Comparison with Predicate Device
Comparison studies were conducted at three sites (one internal and two external reference laboratories) using prospective samples submitted for Lyme serology testing. Five hundred and twenty (520) serum samples were tested on both the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test and on the predicate B. burgdorferi IgG/IgM ELISA Test. The results are summarized in the following table:
| Predicate IgG/IgM ELISA | |||||
|---|---|---|---|---|---|
| Positive | Equivocal* | Negative | Total | ||
| Gold StandardDiagnostics Borreliaburgdorferi IgG/IgMELISA Test Kit | Positive | 55 | 7 | 2 | 64 |
| Equivocal* | 8 | 2 | 9 | 19 | |
| Negative | 2 | 1 | 434 | 437 | |
| Total | 65 | 10 | 445 | 520 |
*Equivocal samples counted as positive
| Positive percent agreement = 96.0% (72/75) | 95% CI (88.8% - 99.2%) |
|---|---|
| Negative percent agreement = 97.5% (434/445) | 95% CI (95.6% - 98.8%) |
Clinical Sensitivity
Sensitivity Study
A sensitivity study was performed on 89 clinically characterized samples encompass early, disseminated, and late stages of Lyme disease. The samples were tested on both the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test and on the predicate B. burgdorferi IgG/IgM ELISA Test. The results are summarized in the following table:
| DiseaseStage | n | Gold StandardDiagnostics Borreliaburgdorferi IgG/IgMELISA Test Kit | PredicateIgG/IgM ELISA |
|---|---|---|---|
| Early | 38 | 76.3% (29/38) | 78.9% (30/38) |
| Disseminated | 15 | 100.0% (15/15) | 100.0% (15/15) |
| Late | 36 | 97.2% (35/36) | 94.4% (34/36) |
CDC Panel
Forty samples of various reactivity were acquired from the Centers for Disease Control (CDC). Of the 40 samples, five were from healthy individuals and 35 were from patients diagnose with Lyme disease and stratified by disease stage. All samples were tested on the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test and on the predicate Borrelia burgdorferi IgG/IgM ELISA Test. The results are summarized in the following table:
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| DiseaseStage | n | Gold Standard DiagnosticsBorrelia burgdorferiIgG/IgM ELISA Test Kit | PredicateIgG/IgM ELISA | ||
|---|---|---|---|---|---|
| PositiveorEquivocal | % Agreementwith ClinicalDiagnosis | PositiveorEquivocal | % Agreementwith ClinicalDiagnosis | ||
| Healthy | 5 | 0 | 100% | 0 | 100% |
| Early(0-2 months) | 15 | 13 | 86.7% | 12 | 80.0% |
| Convalescent(3-12 months) | 13 | 7 | 53.8% | 7 | 53.8% |
| Late(>1 year) | 7 | 7 | 100% | 7 | 100% |
Expected Values
The range of values and positivity rate among different studies and population for the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test are as follows:
| Unit Results | Qualitative Results | |||||
|---|---|---|---|---|---|---|
| Population | # Samples | Mean | Range | Std.Dev. | #Positive/Equivocal | %Positive/Equivocal |
| NormalEndemic | 110 | 5.8 | 0.6 – 11.3 | 2.075 | 3 | 2.7% |
| NormalNon-Endemic | 100 | 4.2 | 0.9 – 12.3 | 2.077 | 2 | 2.0% |
| ProspectiveStudy | 520 | 6.3 | 0.70 - 32.3 | 5.407 | 83 | 16.0% |
| SensitivityStudy | 89 | 25.0 | 3.6 - 34.9 | 8.449 | 79 | 88.8% |
Note: It is recommended that each laboratory determine its own normal range based on the population.
7) Conclusion:
From the comparison data, we conclude that the Gold Standard Diagnostics Borrelia burgdorferi IgG/IgM ELISA Test is substantially equivalent to the Trinity Biotech Captia™ Borrelia burgdorferi IgG/IgM ELISA Test kit (predicate device: K033070).
§ 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).