(265 days)
The Gold Standard Diagnostics Antibody (ANA) Screen ELISA Test Kit is a qualitative assay for the detection of ANAs in human serum. The assay collectively detects in one well ANAs against double stranded DNA (dsDNA), SSA (Ro60 and Ro52), SSB (La), Sm, Sm/RNP, Scl-70, Jo-1, Ribosomal P, and Centromeric antibodies along with sera positive for immunofluorescent HEp-2 ANAs.
The assay is used as an aid in the diagnosis of Systemic Lupus Erythematosus, Mixed Connective Tissue Disease, Sjögren's Syndrome, Progressive Systemic Sclerosis, and Polymyositis/Dermatomyositis, and should be used in conjunction with other laboratory tests and clinical findings.
The assay requires a total of 90 minutes incubation time. The test uses antigen coated on microtiter wells. Serum is added to each well and incubated for 30 minutes at room temperature. If antibodies are present they will bind to the antigen in the well. Unbound serum is removed by washing the wells three times. An HRP-conjugated anti-human IgG is then added to each well and incubated for 30 minutes at room temperature. If antibody is present, it will bind to the antibody attached to the antigen on the well. The wells are again washed three times to remove any unbound conjugate. A TMB substrate is added to each well and incubated for 30 minutes at room temperature. If enzyme is present, it will react with the substrate to generate a colored product. After the incubation period, the reaction is stopped with a Stop Solution and the color intensity is measured spectrophotometrically.
The provided text describes the performance evaluation of the "Gold Standard Diagnostics Anti-Nuclear Antibody (ANA) Screen ELISA Test Kit" and its comparison to a predicate device.
Here's a breakdown of the requested information based on the document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve >X% sensitivity and >Y% specificity"). Instead, it presents the device's performance in comparison to a predicate device and provides clinical sensitivity and specificity for various conditions.
However, we can infer performance targets by looking at the results that demonstrate equivalence or acceptable clinical utility. For the purpose of this analysis, I will present the reported performance of the device, especially concerning agreement with the predicate and clinical sensitivity/specificity.
| Performance Metric | Reported Device Performance (When Equivocal Treated as Positive) | Reported Device Performance (When Equivocal Treated as Negative) |
|---|---|---|
| Agreement with Predicate Device (Overall Results) | ||
| Percent Positive Agreement | 94.9% (C.I. 91.5% - 97.2%) | 92.3% (C.I. 88.4% - 95.2%) |
| Percent Negative Agreement | 92.2% (C.I. 89.7% - 94.2%) | 96.2% (C.I. 94.3% - 97.6%) |
| Overall Agreement | 93.0% (C.I. 91.1% - 95.7%) | 94.9% (C.I. 93.2% - 96.3%) |
| Clinical Performance (against clinical diagnosis - CTD vs. Non-CTD & Others) | ||
| Sensitivity (for Connective Tissue Disease (CTD)) | 83.5% (95% C.I. = 79.1% - 86.0%) | 79.2% (95% C.I. = 75.4% - 82.7%) |
| Specificity (for Non-Connective Tissue Disease & Others) | 96.7% (95% C.I. = 93.6% - 98.6%) | 96.7% (95% C.I. = 93.6% - 98.6%) |
| Overall Agreement (Clinical) | 87.8% (95% C.I. = 85.2% - 90.0%) | 84.9% (95% C.I. = 82.1% - 87.4%) |
| Reproducibility (Qualitative Result Matching Expected) | ||
| Sample 1 (Negative) | 100% (Site 1, 2, 3) | |
| Sample 2 (Equivocal) | 95% (Site 1, 2), 100% (Site 3) | |
| Sample 3 (Positive) | 100% (Site 1, 2, 3) | |
| Precision (Qualitative Result Matching Expected) | ||
| Positive Samples (3) | 100% | |
| Equivocal Sample (1) | 90% | |
| Negative Samples (2) | 90% (one sample), 100% (one sample) | |
| Lot-to-Lot Comparison (Qualitative Result Matching Expected) | ||
| Positive Sample | 100% (all 3 lots) | |
| Equivocal Sample | 100% (all 3 lots) | |
| Negative Sample | 100% (all 3 lots) | |
| Interfering Substances (Mean Percent Inhibition) | ||
| Hemoglobin | -2.1% | |
| Bilirubin | -3.0% | |
| Rheumatoid Factor | 8.8% | |
| Triglycerides | -1.4% | |
| Heterophile (multiple concentrations) | 5.4%, 2.2%, -0.6% | |
| Prozone (Hook) Effect (Max ratio calculated without observing prozone effect) | 12 |
2. Sample size used for the test set and the data provenance
- Test Set for Equivalence to Predicate Device: 848 samples
- Test Set for Clinical Sensitivity/Specificity: 753 samples (510 CTD samples, 243 Non-CTD & others)
- Test Set for Analyte Specificity (initial comparison): 55 samples (5 samples for each of 11 analytes)
- Test Set for Analytical Specificity (CDC & AMLI samples): 20 samples (10 CDC, 10 AMLI)
- Test Set for Precision: 7 samples
- Test Set for Reproducibility: 3 samples tested across 3 sites
- Test Set for Lot-to-Lot Comparison: 3 samples tested across 3 lots
- Test Set for Expected Values (Normal Donors): 99 normal blood donors (51 males, 48 females)
The data provenance is not explicitly stated in terms of country of origin, but it is indicated that the clinical comparison was conducted at three different sites. The samples for clinical sensitivity and specificity were "clinically diagnosed connective tissue and non-connective tissue disease sera." The study is retrospective in the sense that existing samples were tested, not samples collected specifically for a prospective clinical trial.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The document does not specify the number or qualifications of experts for establishing ground truth for the clinical samples. For the comparison to the predicate device, the "ground truth" was essentially the result from the "commercially available Anti-Nuclear Antibody ELISA test," which is the predicate device itself. For the clinical sensitivity/specificity, the ground truth was based on "Clinical Diagnosis" (e.g., Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc)), but the process of how these clinical diagnoses were definitively established is not detailed, nor is the number or qualifications of the clinicians involved.
4. Adjudication method for the test set
The document does not describe an explicit adjudication method (like 2+1 or 3+1) for the test sets. For the comparison to the predicate, it presents the agreement directly. For clinical sensitivity and specificity, it relies on existing clinical diagnoses. For the analytical specificity with CDC and AMLI samples, it states, "All CDC and AMLI samples gave their expected results," implying predefined expected results without mentioning an adjudication process for these specific samples.
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 section is not applicable. The device is an ELISA-based diagnostic test kit, not an AI-assisted diagnostic tool that involves human readers interpreting images or data with and without AI assistance. Therefore, an MRMC study comparing human readers with and without AI assistance was not conducted.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
This concept is not directly applicable in the context of this ELISA test kit. The "device" itself (the ELISA kit) is a standalone test that produces a result (OD Ratio, then converted to units and interpreted as Positive, Equivocal, or Negative). The performance reported for agreement with the predicate and clinical sensitivity/specificity is the standalone performance of the test kit against established comparative methods or clinical diagnoses. There isn't an "algorithm" in the typical sense of AI, but the assay procedure and interpretation rules define its standalone performance.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth used depends on the specific study:
- For comparison with the predicate device: The results from the legally marketed predicate device (Aesku, Inc. Aeskulisa ANA HEp-2) served as the comparative "ground truth."
- For clinical sensitivity and specificity: Clinical diagnoses (e.g., Systemic Lupus Erythematosus (SLE), Mixed Connective Tissue Disease (MCTD), Rheumatoid Arthritis (RA)) were used. It's implied these diagnoses were established through standard clinical practice, though the specifics of that establishment (e.g., expert consensus, pathology, specific diagnostic criteria) are not detailed in this document.
- For analytical specificity (CDC and AMLI samples): These were reference sera with known specificities, so their predefined "expected results" acted as the ground truth.
8. The sample size for the training set
The document does not explicitly mention a "training set" in the context of an algorithm. For an ELISA kit, development typically involves optimizing reagents and protocols. The studies described are performance evaluation studies (test sets) rather than algorithm training.
9. How the ground truth for the training set was established
As there is no "training set" in the sense of machine learning algorithms, this question is not applicable. The development of an ELISA kit involves laboratory optimization and validation, rather than learning from a labeled training dataset.
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JAN 28 2014
510(k) Summary
This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirement of SMDA 1990 and 21 CFR 807.92.
- Gold Standard Diagnostics 1) Submitter's Name: 2851 Spafford St. Davis, CA. 95618 . Address: 530-759-8000 Phone Number: Contact Person: Napoleon Monce January 28, 2014 Date:
-
- Product and Trade Name: Anti-Nuclear Antibody (ANA) Screen ELISA Test
Common Name or Classification Name: Anti-Nuclear Antibody ELISA
Product Code: LJM
-
- Legally marketed device to which the submitter claims equivalence: Aesku, Inc. Aeskulisa ANA HEp-2 K040953.
4) Description of the device:
The assay requires a total of 90 minutes incubation time. The test uses antigen coated on microtiter wells. Serum is added to each well and incubated for 30 minutes at room temperature. If antibodies are present they will bind to the antigen in the well. Unbound serum is removed by washing the wells three times. An HRP-conjugated anti-human IgG is then added to each well and incubated for 30 minutes at room temperature. If antibody is present, it will bind to the antibody attached to the antigen on the well. The wells are again washed three times to remove any unbound conjugate. A TMB substrate is added to each well and incubated for 30 minutes at room temperature. If enzyme is present, it will react with the substrate to generate a colored product. After the incubation period, the reaction is stopped with a Stop Solution and the color intensity is measured spectrophotometrically.
5) Intended use of the device:
The Gold Standard Diagnostics Antibody (ANA) Screen ELISA Test Kit is a qualitative assay for the detection of ANAs in human serum. The assay collectively detects in one well ANAs against double stranded DNA (dsDNA), SSA (Ro60 and Ro52), SSB (La), Sm, Sm/RNP, Scl-70, Jo-1, Ribosomal P, and Centromeric antibodies along with sera positive for immunofluorescent HEp-2 ANAs.
The assay is used as an aid in the diagnosis of Systemic Lupus Erythematosus, Mixed Connective Systemic Sclerosis. and Syndrome, Progressive Sjögren s Tissue Disease,
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Polymyositis/Dermatomyositis and should be used in conjunction with other laboratory tests and clinical findings.
6) Comparison with the predicate device:
The Gold Standard Diagnostics Antinuclear Antibody (ANA) Screen ELISA Test Kit was compared The Gold Daniable Diagnootes Pinnstered by Aesku Inc, the Aeskulisa ANA HEp-2 (K040953). Below are tables comparing the two devices.
| Item | Device | Predicate |
|---|---|---|
| Intended Use | Qualitative assay for the detection of ANAs in human serum. | Same |
| Assay Format | Qualitative | Same |
| Technology | ELISA | Same |
| Calibration | Relative evaluation | Same |
| Assay Platform | 96-well microtiter plates | Same |
| Controls | Cutoff, Positive and Negative | Same |
| Conjugate | IgG Conjugate - Anti Human HRP | Same |
| Substrate | Tetramethylbenzidine (TMB) | Same |
| Procedure | Sample incubations with micro-well antigen coated plate, followed by a wash step, incubation with an anti-human IgG enzyme conjugate, wash step, incubation with substrate, then addition of a stop solution and reading at 450nm. | Same |
| Reported Results | OD Ratio | Same |
| Sample Types | Serum | Same |
| Sample Dilution | 1:101 | Same |
| Differences | ||
|---|---|---|
| Item | Device | Predicate |
| Antigen Mixture | dsDNA, SSA (Ro60 and Ro52), SSB (La),Sm, Sm/RNP, Scl-70, Jo-1, Ribosomal P, andCentromeric antibodies along with serapositive for immunofluorescent HEp-2 ANAS | dsDNA, histones, SSA (Ro),SSB (La), Sm, snRNP/Sm,Scl-70, Jo-1, and Centromericantibodies along with serapositive forimmunofluorescent HEp-2ANAs |
| Diluent | Ready to Use | 5x concentrate |
| Wash Solution | 10x concentrate | 50x concentrate |
| Stop Solution | 1N Sulfuric Acid | 1N Hydrochloric Acid |
| Interpretation | Convert to units. Negative <0.83 units:Equivocal units 0.83-1.2 units; Positive>1.2 units | Convert to Index Value.Negative <1.0 Index Value;Positive >1.0 Index Value |
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6(b1) Nonclinical tests:
Interfering Substances
The effect of potential interfering substances on samples using the Gold Standard Diagnostics Antinuclear Antibody (ANA) Screen ELISA Test was evaluated. Five samples across the reportable range of the assay were spiked with high levels of hemoglobin, bilirubin, rheumatoid factor, and triglycerides. The recommended concentrations from the guideline "Interference Testing In Clinical Chemistry" from the Clinical and Laboratory Standards Institute were used (CLSI EP7-A2). In addition, to assess the interference in the assay from heterophile antibody, two samples at differing unit values were assessed at three concentrations of a Heterophile (HAMA type 1). The tested substances did not affect the performance of the Gold Standard Diagnostics Anti-Nuclear Antibody (ANA) Screen ELISA Test. The results are summarized below:
| Substance | Concentration | Mean PercentInhibition |
|---|---|---|
| Hemoglobin | 2 g/L | -2.1% |
| Bilirubin | 20 mg/dL | -3.0% |
| Rheumatoid Factor | 100 IU/mL | 8.8% |
| Triglycerides | 3000 mg/dL | -1.4% |
| Heterophile | 65 µg/mL | 5.4% |
| Heterophile | 32.5 µg/mL | 2.2% |
| Heterophile | 16.25 µg/mL | -0.6% |
Prozone (Hook) Effect
To evaluate the hook effect on the Gold Standard Diagnostics Anti-Nuclear Antibody (ANA) Screen ELISA Test, sera with high antibody concentration were tested. Five samples with high antibody titers were diluted 1:100 to 1:12,000 and the ratio of the sample OD to cutoff OD was calculated. The maximum ratio calculated without observing a prozone effect was 12.
6(b2): Clinical Comparison:
The performance of the Gold Standard Diagnostics Anti-Nuclear Antibody (ANA) Screen ELISA assay was determined by conducting a correlation study tested at three different sites using a total of 848 samples. The samples were tested on both the Gold Standard Anti-Nuclear Antibody (ANA) Screen ELISA assay and a commercially available Anti-Nuclear Antibody ELISA test. The results are summarized in the following table:
| Predicate Device | ||||
|---|---|---|---|---|
| Overall Results | Positive | Negative | Total | |
| Gold StandardDiagnostics ANAScreen ELISA | Positive | 251 | 22 | 273 |
| Equivocal | 7 | 23 | 30 | |
| Negative | 14 | 531 | 545 | |
| Total | 272 | 576 | 848 |
When the equivocal results are treated as positives, the percent positive agreement, percent negative agreement, and the overall agreement along with their 95% confidence intervals are found to be
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94.9% (C.I. 91.5%% - 97.2%), 92.2 % (C.I. 89.7% - 94.2%), and 93.0 % (C.I. 91.1% - 95.7%), respectively.
When the equivocal results are treated as negatives, the percent positive agreement, percent negative agreement, and the overall agreement along with their 95% confidence intervals are found to be 92.3% % (C.I. 88.4%% - 95.2%), 96.2 % (C.I. 94.3% - 97.6%), and 94.9 % (C.I. 93.2% - 96.3%), respectively.
To demonstrate the test has a performance comparable to that of the individual analyte assays, five samples known to be positive for each analyte (dsDNA, SS-A/Ro 60, SS-A/Ro 52, SS-B, Sm, Sm/RNP, Scl-70, Jo-1, Ribosomal P, Centromere, and HEp-2 IFA, total of 55 samples) were tested on the proposed ANA Screening test, on an FDA-cleared test that measures each analyte individually, and by ANA HEp-2 IFA test. The percentage of the five samples from each analyte that were positive is shown in the following table:
| Samplereactivity | GSD test | DNA | SSA(Ro60) | SSA(Ro52) | SSB | Sm | Sm/RNP | Scl-70 | Jo-1 | RibosomalP | Centromere | Hep-2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| dsDNA | 100% | 100% | 60% | 20% | 20% | 40% | 40% | 0% | 0% | 20% | 0% | 100% |
| SSA (Ro60) | 100% | 60% | 100% | 40% | 20% | 0% | 0% | 0% | 0% | 20% | 0% | 100% |
| SSA (Ro52) | 80% (1equivocal) | 20% | 80% | 100% | 20% | 0% | 0% | 0% | 0% | 0% | 0% | 80% |
| SSB | 100% | 20% (1equivocal) | 100% | 60% | 100% | 0% | 0% | 0% | 0% | 0% | 0% | 100% |
| Sm | 100% | 60% | 0% | 0% | 0% | 100% | 100% | 0% | 0% | 0% | 0% | 100% |
| Sm/RNP | 100% | 80% | 20% | 0% | 0% | 60% | 100% | 0% | 0% | 40% | 0% | 100% |
| SCL-70 | 100% | 20% | 0% | 0% | 0% | 0% | 0% | 100% | 0% | 0% | 0% | 100% |
| Jo-1 | 100% | 0% | 20% | 40% | 0% (1equivocal) | 0% | 0% | 0% | 100% | 0% | 0% | 20% |
| Ribosomal P | 100% | 80% | 40% | 0% | 0% | 0% | 40% | 0% | 0% | 100% | 0% | 80% |
| Centromere | 100% | 0% | 0% | 0% | 0% | 0% | 0% | 0% | 0% | 0% | 100% | 100% |
| Hep-2 | 100% | 40% | 40% | 0% | 20% | 20% | 40% | 20% | 0% | 40% | 0% | 100% |
Analytical Specificity
Ten reference ANA sera from the Centers for Disease Control (CDC) and 10 sera from the Association of Medical Laboratory Immunologist (AMLI) were tested on the Gold Standard Diagnostics Anti-Nuclear Antibody (ANA) Screen ELISA in duplicate. Below are the observed results for each replicate test. All CDC and AMLI samples gave their expected results.
| Sample | Specificity | Result 1 | Result 2 |
|---|---|---|---|
| CDC #1 | DNA | Positive | Positive |
| CDC #2 | SS-A/SS-B | Positive | Positive |
| CDC #3 | RNP, SS-A, SS-B | Positive | Positive |
| CDC #4 | RNP | Positive | Positive |
| CDC #5 | Sm | Positive | Positive |
| CDC #7 | SS-A/Ro | Positive | Positive |
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| CDC #8 | CENP-B | Positive | Positive |
|---|---|---|---|
| CDC #9 | Scl-70 | Positive | Positive |
| CDC #10 | Jo-1 | Positive | Positive |
| CDC #12 | Ribosomal-P | Positive | Positive |
| AMLI #1 | Negative | Negative | Negative |
| AMLI #2 | SS-A/SS-B | Positive | Positive |
| AMLI #3 | SmRNP | Positive | Positive |
| AMLI #4 | SS-A/Ro | Positive | Positive |
| AMLI #5 | SS-A/SS-B | Positive | Positive |
| AMLI #6 | Scl-70 | Positive | Positive |
| AMLI #7 | Jo-1 | Positive | Positive |
| AMLI #8 | CENP-B | Positive | Positive |
| AMLI #9 | dsDNA | Positive | Positive |
| AMLI #10 | Negative | Negative | Negative |
Clinical Sensitivity and Specificity
Clinically diagnosed connective tissue and non-connective tissue disease sera were evaluated on both the proposed device and on the predicate device. The results are summarized in the following tables:
| Clinical Diagnosis | NumberTested | Positive(%) | Equivocal(%) | Negative(%) |
|---|---|---|---|---|
| Systemic LupusErythematosus (SLE) | 322 | 269 (82.9) | 11 (3.4) | 42 (13) |
| Systemic Sclerosis (SSc) | 40 | 29 (72.5) | 1 (2.5) | 10 (25) |
| Polymyositis (PM) | 12 | 4 (33.3) | 2 (16.7) | 6 (50) |
| Dermatomyositis (DM) | 15 | 4 (26.7) | 2 (13.3) | 9 (60) |
| PM or DM Overlap | 5 | 1 (20) | 1 (20) | 3 (60) |
| Myositis | 10 | 4 (40) | 1 (10) | 5 (50) |
| Mixed Connective TissueDisease (MCTD) | 28 | 28 (100) | 0 | 0 |
| Undifferentiated CTD(UTCD) | 3 | 3 (100) | 0 | 0 |
| Sjögren's Syndrome (SjS) | 75 | 63 (84) | 4 (5.3) | 8 (10.7) |
| Total (CTD) | 510 | 405 (79.4) | 22 (4.3) | 83 (16.3) |
| Clinical Diagnosis | NumberTested | Positive(%) | Equivocal(%) | Negative(%) |
|---|---|---|---|---|
| Rheumatoid Arthritis (RA) | 100 | 2 (2) | 0 | 98 (98) |
| Osteoarthritis | 20 | 5 (25) | 0 | 15 (75) |
| Primary Biliary Cirrhosis(PBC) | 8 | 1 (12.5) | 0 | 7 (87.5) |
| Autoimmune Hepatitis(AIH) | 2 | 0 | 0 | 2 (100) |
| Hashimoto's Thyroiditis | 17 | 0 | 0 | 17 (100) |
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| Grave's Disease | 17 | 0 | 0 | 17 (100) |
|---|---|---|---|---|
| Ulcerative Colitis | 5 | 0 | 0 | 5 (100) |
| Celiac Disease | 5 | 0 | 0 | 5 (100) |
| Primary Anti-phospholipidSyndrome (PAPS) | 22 | 0 | 0 | 22 (100) |
| Granulomatosis withpolyangitis (Wegener's) | 5 | 0 | 0 | 5 (100) |
| Total (non-CTD) | 201 | 8 (4) | 0 | 193 (96) |
| Clinical Diagnosis | NumberTested | Positive(%) | Equivocal(%) | Negative(%) |
|---|---|---|---|---|
| Herpes Simplex Virus (HSV) | 7 | 0 | 0 | 7 (100) |
| Epstein Barr Virus (EBV) | 7 | 0 | 0 | 7 (100) |
| Syphilis | 7 | 0 | 0 | 7 (100) |
| Varicella Zoster Virus (VZV) | 7 | 0 | 0 | 7 (100) |
| Mumps | 7 | 0 | 0 | 7 (100) |
| Rheumatoid Factor | 7 | 0 | 0 | 7 (100) |
| Total (other) | 42 | 0 | 0 | 42 (100) |
The clinical sensitivity and specificity compared to the predicate device is summarized in the following tables:
| Overall Results | CTD | Non-CTD & others | ||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| Gold StandardDiagnostics ANAScreen ELISA | Positive | 404 | 8 | 412 |
| Equivocal | 22 | 0 | 22 | |
| Negative | 84 | 235 | 319 | |
| Total | 510 | 243 | 753 | |
| Equivocals considered as Positive: | Sensitivity = 83.5% (95% C.I. = 79.1% - 86.0%)Specificity = 96.7% (95% C.I. = 93.6% - 98.6%)Overall = 87.8% (95% C.I. = 85.2% - 90.0%) | |||
| Equivocals considered as Negative: | Sensitivity = 79.2% (95% C.I. = 75.4% - 82.7%)Specificity = 96.7% (95% C.I. = 93.6% - 98.6%)Overall = 84.9% (95% C.I. = 82.1% - 87.4%) |
Precision
Assessment of the repeatability of the assay was performed on seven samples; three positive samples, one equivocal sample, and three negative samples. One positive sample was diluted with normal human serum to produce a concentration 20% above the positive ratio cutoff (approximately 1.4 U). One negative sample was diluted to 20% below the negative cutoff ratio (approximately 0.70 units). Each sample was tested twice a day for ten days. All the observed results matched the expected results. The results are summarized in the following table:
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| Sample | Mean (U) | Range (U) | Expectedqualitativeresult | % Observedmatchingexpectedresult |
|---|---|---|---|---|
| 1 | 5.60 | 5.18-5.82 | Positive | 100% |
| 2 | 2.56 | 2.13-2.96 | Positive | 100% |
| 3 | 1.36 | 1.24-1.67 | Positive | 100% |
| 4 | 1.06 | 0.93-1.30 | Equivocal | 90% |
| 5 | 0.73 | 0.62-0.90 | Negative | 90% |
| 6 | 0.34 | 0.27-0.38 | Negative | 100% |
| 7 | 0.16 | 0.12-0.20 | Negative | 100% |
Reproducibility
The reproducibility of the assay was done by testing three samples in duplicate for five days, twice a I he reproducibility of the acchnicians per site. The mean results are summarized in the table below.
| Sample | Mean (U) | Site | Range (U) | Expectedqualitative result | % Observedresult matchingexpected result |
|---|---|---|---|---|---|
| 1 | 0.20 | 1 | 0.18-0.24 | Negative | 100% |
| 1 | 2 | 0.18-0.26 | Negative | 100% | |
| 1 | 3 | 0.20-0.27 | Negative | 100% | |
| 2 | 1.45 | 1 | 1.05-1.57 | Equivocal | 95% |
| 2 | 2 | 1.06-1.45 | Equivocal | 95% | |
| 2 | 3 | 1.4-1.55 | Equivocal | 100% | |
| 3 | 3.08 | 1 | 2.94-3.14 | Positive | 100% |
| 3 | 2 | 2.51-3.18 | Positive | 100% | |
| 3 | 3 | 3.04-3.37 | Positive | 100% |
In addition, a lot to lot comparison was performed using three samples, one positive, one equivocal, and one negative sample tested five times each on three different lots. The results are summarized in the table below:
| Sample | Mean (U) | Lot Number | Range (U) | Expectedqualitative result | % Observedresult matchingexpected result |
|---|---|---|---|---|---|
| 1 | 1.474 | 1 | 1.42-1.51 | Positive | 100% |
| 1 | 2 | 1.48-1.60 | Positive | 100% | |
| 1 | 3 | 1.39-1.47 | Positive | 100% | |
| 2 | 0.960 | 1 | 0.92-0.96 | Equivocal | 100% |
| 2 | 2 | 0.92-1.01 | Equivocal | 100% | |
| 2 | 3 | 0.96-1.00 | Equivocal | 100% |
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| 3 | 1 | 0.51-0.58 | Negative | 100% | |
|---|---|---|---|---|---|
| 3 | 0.519 | 2 | 0.50-0.52 | Negative | 100% |
| 3 | 3 | 0.50-0.51 | Negative | 100% |
Expected Values
The expected value for a normal patient is a negative result. However, positive ANA results may be found in apparently healthy individuals. In a study, 12.4% of sera from normal healthy donors gave detectable ANA results (1). To evaluate the expected values, serum from 99 normal blood donors were tested. The mean unit value, standard deviation, and the unit value of the 950 percentile are summarized in the following table:
| NumberTested | Mean Units | SD | 95thPercentile | |
|---|---|---|---|---|
| Normal Healthy Males | 51 | 0.62 | 0.24 | 1.09 |
| Normal Healthy Females | 48 | 0.55 | 0.13 | 0.82 |
(1) Jaskowski TD. Schroder C. et. al. Screening for Antinuclear Antibodies by Enzyme Immunoassay. Am J Clin Path. 105(4): 468-473. 1996.
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Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is a stylized symbol that resembles an eagle or a bird in flight, composed of three curved lines.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 28, 2014
GOLD STANDARD DIAGNOSTICS C/O MR. NAPOLEON MONCE DIRECTOR, PRODUCT DEVELOPEMNT 2851 SPAFFORD ST. DAVIS CA 95618
Re: K131330
Trade/Device Name: Gold Standard Diagnostics Anti-nuclear Antibody (ANA) Screen Elisa Test Kit Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: II Product Code: LJM Dated: December 19, 2013
Received: December 23, 2013
Dear Mr. 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 Parts 801 and 809); medical device reporting (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 Part 820); and if applicable, the
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electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809). please contact 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/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/ReportalProblem/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/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Maria M. Chan -S
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K131330
Device Name
Gold Standard Diagnostics Antinuclear Antibody (ANA) Screen ELISA Test Kit
Indications for Use (Describe)
The Gold Standard Diagnostics Antibody (ANA) Screen ELISA Test Kit is a qualitative assay for the detection of ANAs in human serum. The assay collectively detects in one well ANAs against double stranded DNA (dsDNA), SSA (Ro60 and Ro52), SSB (La), Sm, Sm/RNP, Scl-70, Jo-1, Ribosomal P, and Centromeric antibodies along with sera positive for immunofluorescent HEp-2 ANAs.
The assay is used as an aid in the diagnosis of Systemic Lupus Erythematosus, Mixed Connective Tissue Disease, Sjögren's Syndrome, Progressive Systemic Sclerosis, and Polymyositis/Dermatomyositis, and should be used in conjunction with other laboratory tests and clinical findings.
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)
Please do not write below this line – continue on a separate page if needed.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Elizabeth A. Stafford -S
FORM FDA 3881 (1/14)
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.
§ 866.5100 Antinuclear antibody immunological test system.
(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).