The Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test kit is intended as a qualitative presumptive (first step) test for the detection of 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.

Device Description

The kit includes 12 x 8 well Antigen Coated strips, Conjugate, Substrate, Stop Solution, Wash Buffer, Diluent, Negative Control, Positive Control, and Cutoff 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 IgM antibodies conjugated with horseradish peroxidase is then added, which binds to the antigenantibody 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 450mm.

The antigens used in the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test kit is a combination of B. burgdorferi sensu stricto strain B31 lysate, B. burgdorferi sensu stricto strain 2591 lysate, and a recombinant VlsE protein 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.

AI/ML Overview

The Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test Kit is intended as a qualitative presumptive (first step) test for the detection of 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.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state acceptance criteria in terms of specific thresholds for sensitivity, specificity, or agreement percentages for substantial equivalence. However, the performance metrics are compared against a legally marketed predicate device (Trinity Biotech MarDx Borrelia burgdorferi EIA IgM Test Kit). The demonstration of substantial equivalence relies on favorable comparisons to this predicate.

Approximate "Implied" Acceptance Criteria (Based on Predicate Performance and General Expectations) and Reported Performance:

Performance Metric	Implied Acceptance Criteria (relative to predicate)	Reported Device Performance (Gold Standard Diagnostics IgM ELISA)
PPA (vs. Predicate)	High positive agreement (e.g., >80-90%) compared to the predicate.	90.3% (93/103) with 95% CI (82.9% - 95.5%)
NPA (vs. Predicate)	High negative agreement (e.g., >95%) compared to the predicate.	99.6% (460/462) with 95% CI (98.5% - 99.9%)
2nd Tier PPA	High positive agreement with a Second Tier IgM Blot (e.g., >90%)	98.3% (58/59) with 95% CI (90.9% - 99.9%)
Analytical Specificity (Endemic)	High, likely >90-95%	96.1%
Analytical Specificity (Non-Endemic)	High, likely >90%	90.5%
Precision (CV%)	Within acceptable ranges for ELISA assays (typically <15-20% for low values, lower for moderate/high)	Max CV reported for samples: Within-Run 18.1%, Total 17.9% (Negative control)
Reproducibility (CV%)	Within acceptable ranges for ELISA assays (similar to precision)	Max CV reported for samples: Within-Run 17.0%, Total 18.6% (Negative sample)
Cross-Reactivity	Minimal or explainable cross-reactivity with other conditions.	See table below for specific values.
Interfering Substances	No significant interference from common substances.	None detected
Clinical Sensitivity	Comparable to predicate across disease stages.	Early: 75.9%, Disseminated: 100.0%, Late: 89.7%
CDC Panel Agreement (Healthy)	High agreement for healthy individuals.	93.0%
CDC Panel Agreement (Early Lyme)	Reasonable agreement for early Lyme.	76.7%
CDC Panel Agreement (Other Lyme Stages)	Reasonable agreement for other Lyme stages.	Cardiac: 66.7%, Neurological: 100%, Late: 85.0%
CDC Panel Agreement (Look-alike Disease)	High agreement for look-alike diseases (i.e., low positivity expected).	81.1%

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

Comparison with Predicate Device (Clinical Study):
- Sample Size: 531 serum samples.
- Data Provenance: Prospective samples submitted for Lyme serology testing. Origin not explicitly stated by country, but implies clinical samples from typical patient populations where Lyme serology is performed.
Analytical Specificity:
- Sample Size: 208 asymptomatic individual samples (103 from an endemic region, 105 from a non-endemic region).
- Data Provenance: Not explicitly stated, presumed retrospective acquisition from asymptomatic individuals. No country of origin is mentioned.
Cross-Reactivity:
- Sample Size: 277 samples from serum vendors "who confirmed their positivity for each respective marker."
- Data Provenance: Retrospective acquisition from serum vendors with various infection/disease conditions. No country of origin is mentioned.
Sensitivity Study (Clinically Characterized Samples):
- Sample Size: 114 clinically characterized samples (58 Early, 17 Disseminated, 39 Late stages of Lyme disease).
- Data Provenance: Not explicitly stated, but "clinically characterized" suggests retrospective collection with confirmed diagnoses. No country of origin is mentioned.
CDC Panel:
- Sample Size: 280 positive and negative specimens.
- Data Provenance: Specimens from the Center for Disease Control (CDC). This is a well-characterized, presumably retrospective, panel. The U.S. CDC implies U.S. origin.
Determination of Assay Cutoff:
- Sample Size: 208 normal sera (103 from an endemic region, 105 from a non-endemic region) plus an additional 194 samples (114 from different phases of Lyme disease, 8 negative healthy samples, 72 negative Lyme disease samples with other diseases causing cross-reactivity).
- Data Provenance: Normal sera from endemic/non-endemic regions, and samples representing various Lyme disease phases and other conditions. The provenance is mixed (healthy, disease stages, cross-reactivity).

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

The document does not specify the number or qualifications of experts used to establish the ground truth for any of the test sets.

For the Comparison with Predicate Device and Analytical Specificity studies, the ground truth is indirectly established by the performance of the predicate device and the classification of samples as "asymptomatic" or "submitted for Lyme serology testing," rather than via an expert panel.
For the Cross-Reactivity study, the samples were obtained from "serum vendors who confirmed their positivity for each respective marker." This implies that the ground truth for these samples was based on previous laboratory testing/diagnosis, not explicitly on expert adjudication for this specific study.
For the Sensitivity Study, the samples were "clinically characterized," suggesting that the gold standard was clinical diagnosis, but the process and experts involved are not detailed.
For the CDC Panel, the specimens are described as "masked characterized serum panel," implying the CDC has established the ground truth for these samples (e.g., through clinical diagnosis, Western blot, culture, or other validated methods), but the specific method or experts are not detailed.
The Second Tier Testing uses an "FDA cleared IgM Western blot assay" as a reference standard, which is itself a laboratory test, not expert consensus.

4. Adjudication Method for the Test Set

No explicit adjudication method (e.g., 2+1, 3+1) is mentioned for establishing ground truth for any of the test sets. Ground truth appears to be based on:

The performance of a predicate device for comparison studies.
Clinical characterization or diagnosis for sensitivity studies.
Confirmed positivity by serum vendors or CDC characterization for specificity and panel studies.
FDA-cleared IgM Western blot for second-tier testing.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

This device is an ELISA (Enzyme-Linked Immunosorbent Assay) Test Kit, which is a laboratory diagnostic assay, not an imaging device or AI-driven diagnostic system involving human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This device is a standalone laboratory diagnostic kit. Its performance, as reported in the studies (e.g., PPA, NPA, sensitivity, specificity, precision, reproducibility), represents its standalone performance without a human-in-the-loop component beyond the standard laboratory technician performing the assay. The results are based on objective optical density measurements.

7. The Type of Ground Truth Used

The ground truth used for different studies varies:

Comparison with Predicate Device: The predicate device's results are used as a reference for agreement, not necessarily a true "ground truth" per se but a comparative standard.
Analytical Specificity: Clinical status (asymptomatic, endemic/non-endemic region) is used.
Cross-Reactivity: Confirmed positivity for other markers by serum vendors.
Second Tier Testing: Results from an "FDA cleared IgM Western blot assay."
Sensitivity Study: "Clinically characterized samples," indicating clinical diagnosis based on symptoms, history, and potentially other lab data.
CDC Panel: "Masked characterized serum panel" from the CDC, implying predefined positive/negative status likely based on a combination of clinical information and validated laboratory tests.
Cutoff Determination: Normal sera from endemic/non-endemic regions and samples from different phases of Lyme disease (clinically defined).

8. The Sample Size for the Training Set

Determination of Assay Cutoff:
- 208 normal sera: 103 from an endemic region and 105 from a non-endemic region were used to determine the initial cutoff value (mean plus two standard deviations).
- An additional 194 samples: 114 from different phases of Lyme disease, 8 negative healthy samples, and 72 negative Lyme disease samples with other conditions for cross-reactivity were used for ROC analysis to confirm the cutoff.
- While not explicitly called a "training set" in the context of machine learning, these samples were used to establish and validate the assay's interpretive criteria (cutoff value), which is analogous to how a training set informs a model's parameters.
No other explicit training sets for the device's main performance characteristics are described, as ELISA kits do not typically involve iterative machine learning training in the same way an AI device would.

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

For the samples used in cutoff determination (analogous to a training set):

Normal sera: Presumed to be healthy controls based on their collection from "normal" individuals in endemic and non-endemic regions.
Disease-phase samples: "Clinically characterized samples" and "samples from different phases of Lyme disease" suggest a ground truth established by clinical diagnosis.
Cross-reactivity samples: Negative Lyme disease status with confirmed other conditions.

The establishment of ground truth for these samples aligns with the methods described in point 7.

Summary

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Image /page/0/Picture/0 description: The image contains two logos. On the left is the Department of Health & Human Services logo, which features a stylized caduceus. To the right is the FDA logo, with the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

April 6, 2020

Gold Standard Diagnostics Napoleon Monce Director, Product Development 2851 Spafford St. Davis, California 95618

Re: K200023

Trade/Device Name: Gold Standard Diagnostics Borrelia burgdorferi 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: December 27, 2019 Received: January 6, 2020

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. 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

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-

542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Steven Gitterman, M.D., Ph.D. Deputy Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Image /page/2/Picture/0 description: The image is a logo for Gold Standard Diagnostics. The logo features the words "GOLD STANDARD" in large, bold, black letters. To the left of the words is a gold circle with the letters "GSD" inside. Below the words "GOLD STANDARD" are the words "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.

1. Submitter's Name: Gold Standard Diagnostics Address: 2851 Spafford St. Davis. CA. 95618 Phone Number: 530-759-8000 Contact Person: Napoleon Monce Date: December 27, 2019
1. Product and Trade Name: Gold Standard Diagnostics Borrelia burgdorferi 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

1. Legally Marketed Device to Which the Submitter Claims Equivalence: Trinity Biotech MarDx Borrelia burgdorferi EIA IgM Test Kit (K894293).

4) Description of the Device:

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5) Intended Use of the Device:

6) Comparison with the Predicate Device:

The tables below provide a comparison of the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test kit with the Trinity Biotech MarDx Borrelia burgdorferi EIA IgM Test kit (predicate device: K894293).

Similarities
Item	Subject Device: Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test Kit	Predicate Device: Trinity Biotech MarDx Borrelia burgdorferi EIA IgM Test Kit
Intended Use	The Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test kit is intended as a qualitative presumptive (first step) test for the detection of 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 MarDx Borrelia burgdorferi EIA IgM Test System is a qualitative test intended for use in the presumptive detection of human IgM antibodies to Borrelia burgdorferi in human serum. This EIA system should be used to test serum from patients with a history and symptoms of infection with B. burgdorferi. All positive and equivocal specimens should be retested with a highly specific, second-tier test such as Western blot. Positive second-tier results are supportive evidence of infection with B. burgdorferi. The diagnosis of Lyme disease should be made based on history and symptoms (such as erythema migrans), and other laboratory data, in addition to the presence of antibodies to B. burgdorferi. Negative results (either first or second-tier) should not be used to exclude Lyme disease.
Assay Format	Antigen coated microtiter plate – 96 wells.	Same
Technology	ELISA	Same

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Sample Matrix	Human serum	Same
Sample Processing	Dilute Samples 1:100 in Diluent	Same
Controls Provided	Positive, Cutoff, Negative	Same
Reagents Provided	Diluent, Wash, Conjugate,Substrate, Stop Solution,Absorption Solution	Same
Reported Results	Positive, Equivocal, Negative	Same
Assay Output	Optical density readings fromSpectrophotometer	Same

Differences
Item	Subject Device: Gold StandardDiagnostics Borrelia burgdorferiIgM ELISA Test Kit	Predicate Device: Trinity BiotechMarDx Borrelia burgdorferi EIAIgM Test Kit
Volumes	100ul sample, 50ul substrate, 50ulstop solution	100ul sample, 100ul substrate,100ul stop solution
Incubation	15/15/15 minutes at roomtemperature	30/30/10 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 <0.80Equivocal 0.80-1.19Positive ≥1.2

6(b1): Nonclinical Studies:

Determination of the Assay Cutoff

The cutoff was determined by testing a total of 208 normal sera which consisted of 103 sera from an endemic region of Lyme disease and 105 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. An additional 194 samples consisting of 114 samples from different phases of Lyme disease, 8 negative healthy samples, 72 negative Lyme disease samples but do have other diseases that may cause serologic cross-reactivity, were tested. A receiver operating characteristics (ROC) analysis was performed to evaluate the performance of the assay and confirm that the chosen cutoff provided the best compromise between sensitivity and specificity.

Precision

To determine the precision of the Borrelia burgdorferi 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. Each of the panel members was tested in duplicate, twice per day, for 12

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Sample	N	MeanUnits		Within-Run	Between-Run	Between-Day	Total
ModeratePositive	48	20.6	SD	1.234	0.476	0.423	1.222
			CV	6.0%	2.3%	2.1%	5.9%
LowPositive	48	12.4	SD	0.849	0.728	0.405	0.834
			CV	6.9%	5.9%	3.3%	6.7%
HighNegative	48	5.7	SD	0.740	0.495	0.349	0.727
			CV	13.1%	8.7%	6.2%	12.8%
Negative	48	2.5	SD	0.328	0.103	0.061	0.324
			CV	13.3%	4.2%	2.5%	13.1%
PositiveControl	48	25.2	SD	1.197	0.337	0.492	1.183
			CV	1.3%	1.3%	2.0%	4.7%
CutoffControl	48	9.9	SD	0.317	0.238	0.305	0.287
			CV	3.2%	2.4%	3.1%	2.9%
NegativeControl	48	0.7	SD	0.124	0.052	0.017	0.123
			CV	18.1%	736%	2.5%	17.9%

days. The sample panel was masked and randomized. The results are summarized in the following table:

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-Run, Between-Days, and Between-Sites Standard Deviation and Coefficients of Variation (CV) were calculated. The results are summarized in the following table:

Sample	N	MeanUnits		Within-Run	Between-Run	Between-Day	Between-Sites	Total
ModeratePositive	90	54.4	SD	3.26	1.37	2.49	1.38	3.73
			CV	6.0%	2.5%	4.6%	2.5%	6.9%
LowPositive	90	17.1	SD	1.13	0.46	0.98	0.78	1.29
			CV	6.6%	2.8%	5.7%	4.6%	7.6%
HighNegative	90	6.5	SD	0.60	0.34	0.48	0.56	0.75
			CV	9.2%	5.2%	7.4%	8.6%	11.4%
Negative	90	1.8	SD	0.31	0.25	0.29	0.32	0.34
			CV	17.0%	14.3%	15.9%	17.5%	18.6%
PositiveControl	30	24.2	SD	1.69	1.10	1.28	0.34	1.64
			CV	7.0%	7.0%	5.3%	3.5%	6.8%
CutoffControl	60	9.9	SD	0.36	0.17	0.22	1.33	0.34
			CV	3.6%	1.7%	2.2%	5.5%	3.4%
	30	0.7	SD	0.09	0.03	0.04	0.04	0.72

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Negative Control	CV	13.3%	5.1%	5.1%	5.0%	13.1%
------------------	----	-------	------	------	------	-------

Analytical Specificity

The analytical specificity was determined by testing 208 asymptomatic individuals' samples from endemic and non-endemic regions. The Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test results are summarized in the following table:

	Number of Samples	Number Positive/Equivocal	Analytical Specificity
Endemic Region	103	4	96.1%
Non-endemic Region	105	10	90.5%

Cross Reactivity

A study using 277 samples was conducted to evaluate potential cross reactivity from different infections and 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 IgM ELISA Test. The results are summarized in the following table:

Infection / Diagnosis	Number ofSera Tested	# Positive / (%)
Tick-borne Relapsing Fever IgM	21	0 / (0%)
Treponemal Infections (TPPA)	29	0 / (0%)
Rickettsia IgM	23	0 / (0%)
Ehrlichiosis IgM	10	6 / (60%)*
Babesiosis IgM	16	10 / (63%)*
Leptospirosis IgM	10	8/ (80%)*
H. pylori IgM	10	0 / (0%)
Epstein-Barr Virus IgM	14	0 / (0%)
Varicella Zoster Virus	16	6 / (38%)
Fibromyalgia	25	0 / (0%)
Rheumatoid Arthritis	12	0 / (0%)
Autoimmune Disease	46	0 / (0%)
Multiple Sclerosis	22	0 / (0%)
Severe Periodontitis	23	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 IgM ELISA Test was evaluated. Three samples, a high negative, an equivocal and a low 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" EP07-A3 from the Clinical and Laboratory

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Standards Institute were used (see table below). The tested substances did not affect the performance of the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test.

Substance	Concentration	Interference
Albumin	60 mg/ml	None detected
Bilirubin	0.4 mg/ml	None detected
Cholesterol	4.0 mg/ml	None detected
Hemoglobin	10 mg/ml	None detected
Triglycerides	15 mg/ml	None detected

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 thirty one (531) serum samples were tested on both the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test and on the predicate B. burgdorferi IgM ELISA Test. The results are summarized in the following table:

	Predicate IgM ELISA
	Positive	Equivocal*	Negative	Total
Gold Standard DiagnosticsBorrelia burgdorferi IgMELISA Test Kit	Positive	72	9	5	86
	Equivocal*	4	8	5	17
	Negative	1	9	418	428
	Total	77	26	428	531

*Equivocal samples counted as positive

Positive percent agreement = 90.3% (93/103)
Negative percent agreement = 99.6% (460/462)

95% CI (82.9% - 95.5%) 95% CI (98.5% - 99.9%)

Second Tier Testing

All positive and equivocal samples by the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test and by the Predicate IgM ELISA were tested by an FDA cleared IgM Western blot assay. The results are summarized in the following table:

	Tier 1 Positiveor Equivocal	IgM BlotPositive	IgM BlotNegative
Predicate IgM ELISA	103	59	44
Gold StandardDiagnostics Borreliaburgdorferi IgMELISA Test Kit	103	61	42
Predicate IgM ELISA+	93	58	35

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Gold StandardDiagnostics Borrelia
burgdorferi IgM
ELISA Test Kit

2nd Tier Percent Agreement
2nd Tier PPA(95% CI)	98.3%(90.9% - 99.9%)	58/59

Clinical Sensitivity

Sensitivity Study

A sensitivity study was performed on 114 clinically characterized samples. The samples encompass early, disseminated, and late stages of Lyme disease. The samples were tested on both the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test and on the predicate B. burgdorferi IgM ELISA Test. The results are summarized in the following table:

DiseaseStage	n	Gold StandardDiagnostics Borreliaburgdorferi IgMELISA Test Kit	PredicateIgM ELISA
Early	58	75.9% (44/58)	77.6% (45/58)
Disseminated	17	100.0% (17/17)	100.0% (17/17)
Late	39	89.7% (35/39)	84.6% (33/39)

CDC Panel

A panel of 280 positive and negative specimens from the Center of Disease Control (CDC) for Lyme disease detection was tested on both the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test and on the predicate device. The results are presented as a means to convey further information on the performance of the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test with a masked characterized serum panel. This does not imply an endorsement of the assay by the CDC. The results are summarized in the following table:

Disease Stage	n	Gold Standard DiagnosticsBorrelia burgdorferi IgMELISA Test Kit		PredicateIgM ELISA
		PositiveorEquivocal	% Agreementwith ClinicalDiagnosis	PositiveorEquivocal	% Agreementwith ClinicalDiagnosis
Healthy	100	7	93.0%	14	86.0%
Early Lyme	60	46	76.7%	48	80.0%
Cardiac Lyme	3	2	66.7%	2	66.7%

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Neurological Lyme	7	7	100%	7	100%
Late	20	17	85.0%	17	85.0%
Look-alikeDisease	90	17	81.1%	25	72.2%

Expected Values

The range of values and positivity rate among different studies and population for the Gold Standard Diagnostics Borrelia burgdorferi IgM ELISA Test are as follows:

		Unit Results			Qualitative Results
Population	# Samples	Mean	Range	Std.Dev.	#Positive/Equivocal	%Positive/Equivocal
NormalEndemic	103	3.5	0.4 - 10.7	2.341	4	3.9%
NormalNon-Endemic	105	4.2	0.0 - 15.5	3.136	10	9.5%
ProspectiveStudy	531	7.7	0.0 - 76.6	11.742	103	19.4%
SensitivityStudy	114	32.6	0.0 - 81.0	21.138	96	84.2%

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 IgM ELISA Test is substantially equivalent to the Trinity Biotech MarDx Borrelia burgdorferi EIA IgM Test kit (predicate device: K894293).

Regulation Number and Section

§ 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).