(204 days)
Not Found
No
The description focuses on standard immunoassay technology and image processing for signal measurement, without mentioning AI or ML algorithms for analysis or interpretation.
No.
The device is an in vitro diagnostic test system used to detect antibodies for diagnostic purposes, not to treat or therapeutically benefit a patient.
Yes
The "Intended Use / Indications for Use" section explicitly states that the test system is intended "to aid in the diagnosis of systemic lupus erythematosus, Sjögren's syndrome, scleroderma and myositis," and that it is "for in vitro diagnostic use."
No
The device description clearly states it is a "microarray-based immunoassay" and utilizes a "BeadChip™ microarray on a silicon chip," which are hardware components. The software is used to process the fluorescent signal from this hardware.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "This test is for in vitro diagnostic use."
- Intended Use: The device is intended for testing human serum for the presence of antibodies to aid in the diagnosis of specific diseases. This is a classic definition of an in vitro diagnostic test.
- Device Description: The description details a laboratory-based immunoassay using human serum samples.
- Intended User / Care Setting: The description of the study sites (CLIA and ASHI certified laboratories) further supports its use in a clinical laboratory setting for diagnostic purposes.
N/A
Intended Use / Indications for Use
The BioArray Solutions ENA IgG BeadChip™ Test System is intended for use in testing human serum for the presence of human IgG class antibodies to six extractable nuclear antigens, SSA, SSB, Sm, Sm/RNP, Scl-70, and Jo-1. The presence of these autoantibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of systemic lupus erythematosus, Sjögren's syndrome, scleroderma and myositis. This ENA IgG BeadChip is for use with Array Imaging System 400 (AIS400). This test is for in vitro diagnostic use.
Product codes (comma separated list FDA assigned to the subject device)
LLL
Device Description
The ENA IqG BeadChip™ Test System is a randomly encoded microarray-based immunoassay for antibodies to extractable nuclear antigens. The device is designed to detect IgG class antibodies in human serum to six extractable nuclear antigens: SSA, SSB, Sm, RNP/Sm, Jo-1, and SCL-70. Each antigen is covalently immobilized to a spectrally distinguishable bead type. A and of bead types is constructed by mixing all of the bead types of interest including antigen beads, positive control beads, negative control beads, and system control beads. The bead mixture is immobilized as a BeadChip™ microarray on a silicon chip allowing for the simultaneous detection of the auto-antibodies of interest by the AIS 400.
The ENA IgG BeadChip™ Test System kit will contain adequate reagents for 96 assays.
Patient samples are diluted prior to incubation with the BeadChip microarray. If ENA specific antibodies are present in the sample, they will bind to the immobilized antigen on one or more bead types. After washing the unbound serum from the BeadChip, Alexa-Fluor 647 conjugated goat anti-human IgG is added to the BeadChip and briefly incubated. After removing unbound detection conjugate, the BeadChip is imaged with the Array Imaging System 400 (AIS 400) to measure the fluorescent signal associated with the conjugate bound on individual beads. The average signal intensity, coefficient of variance of the intensities, and the number of beads measured for each type is determined and reported. The ENA Analysis program imports the instrument results, assesses the validity of the internal controls, and generates test results.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Performance comparison study to predicate device, Reproducibility study (day-to-day, operator-to-operator, site-to-site), Normal range and cutoff determination and analytical sensitivity, Cross-reacting and interference substances.
Sample Size:
- Method Comparison Study: 229 samples for each antigen (SSA, SSB, Sm, RNP/Sm, Jo-1, SCL-70) for comparison with predicate.
- Day to Day Reproducibility: Pooled positive sample (PDP) and pooled normal serum sample (PNS). ENA IgG BeadChip assay performed in duplicate for ten consecutive days (20 runs per sample) using three lots of BeadChips.
- Operator-to-operator reproducibility: Pooled positive control, pooled negative control, and ten disease positive samples. Two researchers performed assays in duplicate.
- Site to site reproducibility: Identical serum samples (commercially obtained). 176 samples (52 normal, approximately 25 positive for each antigen). Total of 192 samples run at each site.
- Normal range and cutoff determination: 130 normal samples from healthy, asymptomatic human subjects.
- Analytical sensitivity - limit of blank: Seven assays performed with sample diluent.
- Cross Reacting Substances (Anti-ds-DNA antibodies): Six purchased samples characterized as positive for anti-ds-DNA.
- Cross Reacting Substances (Rheumatoid Factor): Not specified, but "one sample" and "other RF samples" mentioned.
- Interference Substances (Hemolytic and lipidemic samples): One hemolytic sample, one lipidemic sample. Added at 1:10 dilution to pooled positive control.
- Interference Substances (Hemoglobin and Bilirubin): PDP-90 samples.
Key Results:
- Method Comparison Study (Table 2):
- SSA: % Positive Agreement 95.9%, % Negative Agreement 94.1%
- SSB: % Positive Agreement 100.0%, % Negative Agreement 96.1%
- Sm: % Positive Agreement 98.0%, % Negative Agreement 94.0%
- RNP/Sm: % Positive Agreement 100.0%, % Negative Agreement 91.7%
- Jo-1: % Positive Agreement 100.0%, % Negative Agreement 99.5%
- SCL-70: % Positive Agreement 91.2%, % Negative Agreement 98.9%
- Total Agreement percentages range from 93.6% to 99.6%.
- Day to Day Reproducibility (Table 3): Intra-lot CV(%) values typically ranged from 7.3% to 15.9%, and Inter-lot CV(%) values typically ranged from 10.7% to 14.9%.
- Operator-to-operator reproducibility (Table 4): CVs were less than 10% for all positive signals. CV for pooled negative control (PNS-10) for weak nonspecific signals were higher (e.g., 127.18% for SSA, 67.82% for SSB).
- Site to site reproducibility (Table 5): Total agreement of positive/negative calls between two sites: SSA (97.2%), SSB (95.6%), Sm (96.7%), RNP/Sm (90.6%), Jo-1 (97.2%), and SCL-70 (96.1%).
- Normal Range and Cutoff (Table 6): Positive Cutoff for all antigens set at 100.
- Cross Reacting Substances (Anti-ds-DNA antibodies): No cross-reaction was detected from the anti-ds-DNA antibodies.
- Cross Reacting Substances (Rheumatoid Factor): No cross-reaction was detected from the rheumatoid factor.
- Interference Substances (Hemolytic and lipidemic samples): Hemolytic sample did not have significant effect. Lipidemic sample showed apparent interference, including inhibition of protein L activity, resulting in chip QC failure.
- Interference Substances (Hemoglobin and Bilirubin): Bilirubin at 10, 20, and 40 mg/dl and hemoglobin at 250, 500, and 1000 mg/dl were not found to interfere within tested limits.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Percent Positive Agreement / Percent Negative Agreement for method comparison.
- Relative Activity (RA), Standard Deviation (SD), Coefficient of Variance (CV) for reproducibility studies.
- Mean, SD, and Cutoff values for normal range and analytical sensitivity.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.5100 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).
0
510(k) SUMMARY
MAY 3 1 2005
"This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92."
THE ASSIGNED 510(K) NUMBER: K043067
| SUBMITTED BY: | BioArray Solutions, Ltd.
35 Technology Drive, Suite 100
Warren, NJ 07059
(908) 226-8200 (voice), (908) 226-0800 (fax) |
|----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------|
| CONTACT PERSON: | Kevin Wyckoff
Quality Assurance & Regulatory Affairs, Manager |
| Extension: | 215 |
| Email: | kwyckoff@bioarrays.com |
| DATE OF PREPARATION: | April 4, 2005 |
| DEVICE NAME: | ENA IgG BeadChip™ Test System on the Array Imaging
System (AIS 400) |
| CLASSIFICATION NAME: | Antinuclear antibody immunological test system
(21 CFR 866.5100) |
| PREDICATE DEVICE: | ENA IgG ImmuStrip™ Test System
Distributed by SLR Research Corporation
Cleared on April 8, 1995 under document number K964787
by Mardx Diagnostics. |
INTENDED USE
The BioArray Solutions ENA IgG BeadChip™ Test System is intended for use in testing human serum for the presence of human IgG class antibodies to six extractable nuclear antigens, SSA, SSB, Sm, Sm/RNP, Scl-70, and Jo-1. The presence of these autoantibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of systemic lupus erythematosus, Sjögren's syndrome, scleroderma and myositis. This ENA IgG BeadChip is for use with Array Imaging System 400 (AIS400). This test is for in vitro diagnostic use.
DEVICE DESCRIPTION
The ENA IqG BeadChip™ Test System is a randomly encoded microarray-based immunoassay for antibodies to extractable nuclear antigens. The device is designed to detect IgG class antibodies in human serum to six extractable nuclear antigens: SSA, SSB, Sm, RNP/Sm, Jo-1, and SCL-70. Each antigen is covalently immobilized to a spectrally distinguishable bead type. A and of bead types is constructed by mixing all of the bead types of interest including antigen beads, positive control beads, negative control beads, and system control beads. The bead mixture is immobilized as a BeadChip™ microarray on a silicon chip allowing for the simultaneous detection of the auto-antibodies of interest by the AIS 400.
BioArray Solutions, Ltd.
1
The ENA IgG BeadChip™ Test System kit will contain adequate reagents for 96 assays.
Patient samples are diluted prior to incubation with the BeadChip microarray. If ENA specific antibodies are present in the sample, they will bind to the immobilized antigen on one or more bead types. After washing the unbound serum from the BeadChip, Alexa-Fluor 647 conjugated goat anti-human IgG is added to the BeadChip and briefly incubated. After removing unbound detection conjugate, the BeadChip is imaged with the Array Imaging System 400 (AIS 400) to measure the fluorescent signal associated with the conjugate bound on individual beads. The average signal intensity, coefficient of variance of the intensities, and the number of beads measured for each type is determined and reported. The ENA Analysis program imports the instrument results, assesses the validity of the internal controls, and generates test results.
CHARACTERISTIC COMPARISON TO PREDICATE DEVICE
This ENA IgG BeadChip™ Test System is substantially equivalent in principle and clinical performance to the currently marketed ENA IgG ImmuStrip™ Test System marketed by SLR Research for the detection of extractable antinuclear antibodies. Similarities and differences between the procedures and ENA IgG test kits are described in Table 1.
| DEVICE | PREDICATE |
|---|---|
| A. Similarities | |
| Intended Use. The BioArray Solutions ENA | |
| BeadChip™ is intended for use in testing | |
| human serum for the presence of human IgG | |
| class antibody to extractable nuclear antigens | |
| (ENA): SSA, SSB, Sm, Sm/RNP, Scl-70, and | |
| Jo-1, as an aid in the diagnosis of autoimmune | |
| diseases, such as systemic lupus | |
| erythematosus, Sjogren's syndrome, | |
| sclerodema, and myositis. This test is for in | |
| vitro diagnostic use. | The SLR ENA IgG Immustrip™ Test System |
| is intended for use in testing human serum | |
| for the presence of human IgG to extractable | |
| nuclear antigens, as an aid in the diagnosis | |
| of autoimmune disease, such as systemic | |
| lupus erthematosus, Sjögren's syndrome, | |
| sclerodema, and myositis. | |
| Assay type - Immunoassay | |
| Antigens - SSA, SSB, Sm, Sm/RNP, Scl-70, | |
| Jo-1 | |
| Reporter conjugate - Alexa Fluor 647 | |
| Assay Format - Qualitative | |
| Sample Type - Serum | Immunoassay |
| SSA, SSB, Sm, Sm/RNP, Scl-70, Jo-1 | |
| Alkaline Phosphatase | |
| Qualitative | |
| Serum | |
| B. Differences | |
| Substrate - Microparticle | |
| Incubation Time - 30/15 minutes | |
| Method of Detection - Fluorometer | Strip |
| 30/30/15 minutes | |
| Visual |
Table 1 - Comparison with Predicate
NON-CLINICAL PERFORMANCE DATA.
Non-clinical performance data has been submitted to address the following aspects: Performance comparison study to predicate device
Reproducibility study: over-time, operator-to-operator, and site-to-site comparison. Normal range and cutoff determination and analytical sensitivity. Cross-reacting and interference substances
Expiry date is two weeks from date of manufacture.
2
SUMMARY OF PERFORMANCE DATA AND CONCLUSION.
A summary of the method comparison study results is listed in Table 2. The data submitted in this 510(K) Premarket Notification supports the finding that this product is substantially this o ro(r) i remainer rotheansed use, assay principle, and safety features to the legally equiraliant with rooped to the the entere, we believe that this device meets the requirement for a "Substantial Equivalence" decision in accordance with the 510(k) guidelines.
| Predicate/
BeadChip | POS/POS | NEG/NEG | POS/NEG | NEG/POS | EQU/ND | Total | % Postive
Agreement | % Negative
Agreement |
|------------------------|---------|---------|---------|---------|--------|-------|------------------------|-------------------------|
| SSA | 47 | 159 | 2 | 10 | 11 | 229 | 95.9 | 94.1 |
| SSB | 21 | 195 | 0 | 8 | 5 | 229 | 100.0 | 96.1 |
| Sm | 48 | 156 | 1 | 10 | 14 | 229 | 98.0 | 94.0 |
| RNP/Sm | 50 | 155 | 0 | 14 | 10 | 229 | 100.0 | 91.7 |
| Jo-1 | 21 | 204 | 0 | 1 | 3 | 229 | 100.0 | 99.5 |
| SCL-70 | 31 | 183 | 3 | 2 | 10 | 229 | 91.2 | 98.9 |
Table 2 - Summary of Method Comparison Study Results
| | BeadChip | | | | | % Positive
Agreement | % Negative
Agreement | % Total
Agreement |
|-----------|-----------|----------|-----|-----------|-----------|-------------------------|-------------------------|----------------------|
| SSA | POS | NEG | EQU | sub-total | | | | |
| | POS | 47 | 2 | 1 | 49 | 95.9% | 94.1% | 94.5% |
| Predicate | NEG | 10 | 159 | 8 | 169 | | | |
| | ND | 1 | 1 | | | (47/49) | (159/169) | (206/218) |
| | sub-total | 57 | 161 | | 218 | | | |
| SSB | | BeadChip | | | | % Positive
Agreement | % Negative
Agreement | % Total
Agreement |
| | | POS | NEG | EQU | sub-total | | | |
| Predicate | POS | 21 | 0 | 0 | 21 | 100.0% | 96.1% | 96.4% |
| | NEG | 8 | 195 | 5 | 203 | | | |
| | ND | 0 | 0 | | | (21/21) | (195/203) | (216/224) |
| sub-total | | 29 | 195 | | 224 | | | |
| Sm | | BeadChip | | | % Positive
Agreement | % Negative
Agreement | % Total
Agreement | |
|-----------|-----------|----------|-----|-----|-------------------------|-------------------------|----------------------|-----------|
| | | POS | NEG | EQU | sub-total | | | |
| Predicate | POS | 48 | 1 | 0 | 49 | 98.0% | 94.0% | 94.9% |
| | NEG | 10 | 156 | 13 | 166 | | | |
| | ND | 1 | 0 | | | (48/49) | (156/166) | (204/215) |
| | sub-total | 58 | 157 | | 215 | | | |
| Sm/RNP | | | | BeadChip | | % Positive
Agreement | % Negative
Agreement | % Total
Agreement |
|-----------------------------------------|-----------|-----|-----|----------|-----------|-------------------------|-------------------------|----------------------|
| | | POS | NEG | EQU | sub-total | | | |
| | POS | 50 | 0 | 0 | 50 | 100.0% | 91.7% | 93.6% |
| | NEG | 14 | 155 | 9 | 169 | | | |
| Predicate
BioArray Solutions, Ltd. 1 | ND | | 0 | | | (50/50) | (155/169) | |
| | sub-total | 64 | 155 | | 219 | | | |
3
| Jo-1 | | BeadChip | | | | % Positive
Agreement | % Negative
Agreement | % Total
Agreement |
|-----------|-----|----------|-----|-----|-----------|-------------------------|-------------------------|----------------------|
| | | POS | NEG | EQU | sub-total | | | |
| Predicate | POS | 21 | 0 | 0 | 21 | 100.0% | 99.5% | 99.6% |
| | NEG | 1 | 204 | 3 | 205 | | | |
| | ND | 0 | 0 | | | (21/21) | (204/205) | (225/226) |
| sub-total | | 22 | 204 | | 226 | | | |
| SCL-70 | | BeadChip | | | | % Positive
Agreement | % Negative
Agreement | % Total
Agreement |
|-----------|-----------|----------|-----|-----|-----------|-------------------------|-------------------------|----------------------|
| | | POS | NEG | EQU | sub-total | | | |
| Predicate | POS | 31 | 3 | 9 | 34 | 91.2% | 98.9% | 97.7% |
| | NEG | 2 | 183 | 1 | 185 | | | |
| | ND | 0 | 0 | | | (31/34) | (183/185) | (214/219) |
| | sub-total | 33 | 186 | | 219 | | | |
Reproducibility Studies -
Day to day reproducibility. The day-to-day reproducibility study was conducted with a pooled positive sample (PDP) containing antibodies to SSA, SSB, Sm, Sm/RNP, Jo-1, and SCL-70 and a pooled normal serum sample (PNS). The ENA IgG BeadChip assay was performed in duplicate for ten consecutive days for a total of twenty runs per sample using three lots of BeadChips. The pooled positive and negative controls were prepared, aliquoted, and stored in a –20°C freezer. A new aliquot was used each day to prepare fresh dilutions. The three lots of BeadChips were manufactured from three independently coupled ENA bead libraries.
The results for the pooled positive sample are reported by antigen, including the mean of the relative activity (RA), standard deviation (SD), and the coefficient of variance (CV) for each lot (intra-lot reproducibility) and the MEAN, SD, and CV of relative activity of all three lots (inter-lot reproducibility). The RA is the ratio between the antigen Normalized Intensity (NMI) and the lot specific cutoff multiplied by 100. Please refer to the Normal Range/Cutoff section in the original submission for further information regarding the cutoff values.
Negative sample were studied and the results were acceptable
Table 3 - Day to Day Reproducibility - Pooled Positive Sample
| INTRA-LOT 10-DAY
| REPRODUCIBILITY | RELATIVE ACTIVITY (RA) | SSA | SSB | Sm | RNP/Sm | Jo-1 | SCL-70 | |
|---|---|---|---|---|---|---|---|---|
| Lot-A (n=20) | MEAN | 826.1 | 423.4 | 661.1 | 1016.0 | 458.6 | 123.3 | |
| SD | 92.5 | 50.7 | 78.6 | 125.3 | 62.2 | 14.0 | ||
| CV(%) | 11.2 | 12.0 | 11.9 | 12.3 | 13.6 | 11.3 | ||
| Lot-B (n=20) | MEAN | 890.3 | 435.4 | 777.6 | 1198.9 | 549.8 | 135.3 | |
| SD | 76.1 | 64.4 | 123.3 | 120.1 | 69.1 | 18.6 | ||
| CV(%) | 8.5 | 14.8 | 15.9 | 10.0 | 12.6 | 13.7 | ||
| Lot-C (n=20) | MEAN | 776.5 | 442.7 | 751.1 | 1115.6 | 522.8 | 136.3 | |
| SD | 56.4 | 37.4 | 87.7 | 88.8 | 54.7 | 15.0 | ||
| CV(%) | 7.3 | 8.4 | 11.7 | 8.0 | 10.5 | 11.0 | ||
| INTER- | ||||||||
| LOT | Lot-A,B,C | |||||||
| (n=60) | MEAN | 831.0 | 433.9 | 730.0 | 1110.2 | 510.4 | 131.6 | |
| SD | 88.6 | 51.7 | 109.0 | 133.9 | 72.4 | 16.8 | ||
| CV(%) | 10.7 | 11.9 | 14.9 | 12.1 | 14.2 | 12.7 |
4
Operator-to-operator reproducibility. The operator reproducibility was conducted with the pooled positive control, the pooled negative control, and ten disease positive samples. Two researchers performed the ENA IgG BeadChip assays in duplicate. The results are summarized in Table 4, including the mean, standard deviation, and CVs of the relative activity. The CVs were less than 10% for all positive signals; PNS-10 is a pooled negative control and the CV for the weak nonspecific signals for each antigen are much higher compared to disease positive markers.
| Sample ID | Marker | MeanRA | SDRA | CV (%) |
|---|---|---|---|---|
| AAB206 | Sm | 312.2 | 29.7 | 9.52 |
| AAB206 | Sm/RNP | 594.1 | 44.4 | 7.47 |
| AAB237 | Sm/RNP | 512.9 | 40.3 | 7.86 |
| AAB241 | SSA | 848.3 | 61.8 | 7.28 |
| AAB266 | SSA | 860.8 | 35.3 | 4.10 |
| AAB266 | SSB | 341.8 | 12.3 | 3.59 |
| AAB273 | SSB | 612.8 | 33.3 | 5.43 |
| AAB293 | SCL-70 | 90.8 | 7.6 | 8.42 |
| AAB297 | SCL-70 | 111.4 | 9.5 | 8.50 |
| AAB313 | Jo-1 | 281.0 | 24.4 | 8.68 |
| AAB315 | Jo-1 | 262.8 | 14.0 | 5.32 |
| AAB376 | Sm | 401.7 | 37.8 | 9.42 |
| PDP-30 | SSA | 352.6 | 22.7 | 6.44 |
| PDP-30 | SSB | 218.1 | 10.3 | 4.70 |
| PDP-30 | Sm | 419.0 | 9.3 | 2.23 |
| PDP-30 | Sm/RNP | 596.5 | 5.7 | 0.95 |
| PDP-30 | Jo-1 | 280.2 | 25.4 | 9.05 |
| PDP-30 | SCL-70 | 76.4 | 2.9 | 3.77 |
| PNS-10 | SSA | 7.4 | 9.4 | 127.18 |
| PNS-10 | SSB | 3.8 | 2.6 | 67.82 |
| PNS-10 | Sm | 13.3 | 3.0 | 22.74 |
| PNS-10 | Sm/RNP | 28.3 | 6.5 | 23.12 |
| PNS-10 | Jo-1 | 14.2 | 4.0 | 28.25 |
| PNS-10 | SCL-70 | 16.4 | 1.9 | 11.83 |
Table 4 - Operator to Operator Reproducibility
Note:
- Two researchers performed the assay in duplicate, separately (4 runs in total). 2) PNS-10: 1:10 diluted pooled normal serum sample 3) PDP-30: 1:30 diluted pooled disease positive sample
Site to site reproducibility. A site-to-site reproducibility study was performed to assess the assay variability between sites, instruments, and operators. Identical serum samples (commercially obtained) were provided to the three testing sites for on-site testing. A histocompatibility and immunocompatibility laboratory holding both CLIA and ASHI certifications was used as one of the testing sites. The second site was a CLIA certified laboratory specializing in providing diagnostic services related to women's health. BioArray Solutions in-house facilities were used for the third site. These samples were randomly encoded to eliminate any references to identity or diagnosis prior to distributing the samples to the investigational sites. A total of 176 samples comprised of 52 normal samples and approximately 25 positive samples for each antigen were used. A total of 192 samples were run at each site. Ten samples were excluded due to specimen control failure at one or more sites and one sample was excluded due to a sample preparation error. Results for two samples for the Scl-70 marker were excluded due to cluster QC failure at one site. These samples were not repeated at that site.
Comparative analysis of the results obtained from two sites showed that the total agreement of positive/negative calls between two sites for SSA, SSB, Sm, Sm/RNP, JO-1, and SCL-70 is 97.2%, 95.6%, 96.7%, 90.6%, 97.2% and 96.1% respectively.
5
| | +/+/+ | -/- | ?/?/? | -/? | +/? | +/- | Total # | Total
Agreement
(%) |
|--------|--------------|--------------|---------------|-----|-----|-----|---------|---------------------------|
| SSA | 38 | 138 | | 3 | 2 | | 181 | 97.2 |
| SSB | 35 | 137 | 1 | 5 | 2 | 1 | 181 | 95.6 |
| SM | 40 | 135 | | 5 | 1 | | 181 | 96.7 |
| RNP/Sm | 38 | 125 | 1 | 15 | 1 | 1 | 181 | 90.6 |
| Jo-1 | 37 | 138 | 1 | 3 | 1 | 1 | 181 | 97.2 |
| SCL-70 | 27 | 144 | 1 | 5 | 2 | | 179 | 96.1 |
| Note: | (+) Positive | (-) Negative | (?) Equivocal | | | | | |
Table 5 - Three Site Comparison of 181 Assays including Positive and Negative Controls
Normal Range, Cutoff, and Analytical sensitivity
Normal range and cutoff. To determine the normal range for each antigen in the ENA IgG Beadchip assay, one hundred thirty normal samples from healthy, asymptomatic human subjects were assayed. The mean and standard deviation of the relative activity (RA) is listed in Table 6. The upper limit of the normal range for each antigen is the mean plus 3~3.5 standard deviations (SD) and the lower limit of the positive range (Cutoff) for each antigen is the mean plus six SD.
| (RA Value) | SSA | SSB | Sm | Sm/RNP | Jo-1 | SCL-70 |
|---|---|---|---|---|---|---|
| Data Points Used | 130 | 130 | 129 | 130 | 130 | 130 |
| MEAN | 5.7 | 6.0 | 11.6 | 16.7 | 9.2 | 21.0 |
| SD | 15.9 | 15.5 | 15.0 | 14.0 | 15.1 | 13.2 |
| Upper limit - normal range | 60 | 60 | 60 | 60 | 60 | 60 |
| Positive Cutoff | 100 | 100 | 100 | 100 | 100 | 100 |
Table 6 - Cutoff Determination
Note: One sample was eliminated for the Sm antigen using the Dixon D/R ratio method (NCCLS C28-A2).
Analytical sensitivity- limit of blank. To determine the sensitivity of the limit of blank was determined using assays performed with sample diluent in place of serum during the sample incubation. A total of seven assays were performed. The mean and SD of the RA for each antigen are given in Table 7.
| Table 7 - Limit of Blank with Sample Diluent | ||||
|---|---|---|---|---|
| -- | -- | -- | -- | ---------------------------------------------- |
| RA | SSA | SSB | Sm | RNP/Sm | Jo-1 | SCL-70 |
|---|---|---|---|---|---|---|
| Mean | 2.4 | 0.3 | 2.0 | 2.9 | 0.4 | 1.2 |
| STD | 3.6 | 1.3 | 0.7 | 2.9 | 0.7 | 0.3 |
| Mean+3xSTD | 13.3 | 4.2 | 4.1 | 11.6 | 2.4 | 2.1 |
6
Cross Reacting Substances
Anti-ds-DNA antibodies. To test whether the anti-ds-DNA antibodies cross-react with the BeadChip ENA antigen panel, six purchased samples characterized by the vendor as positive for anti-ds-DNA were tested side by side with the BeadChip and the predicate device. Both the BeadChip and the were tested anti-SSA reactivity in three of the six samples. In addition, two of the three predicate dolotics and GSA also tested positive for anti-SSB antibodies with the BeadChip but not with the predicate. Competitive inhibition assays confirmed that the observed anti-SSA and anti-SSB with the predicate. Oompokine finnishion addres. No cross-reaction was detected from the anti-ds-DNA antibodies.
Rheumatoid Factor (RE). To test whether rheumatoid factor cross-reacts with the BeadChip ENA rdicumator ruscer (* ); } + + + + + = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = annigen partify the BeadChip. One sample showed weak anti-SSA and anti-RNP activities while were toolou with the betivity to any antigen. The RF samples were spiked into a weak positive the other and reading to and observed activity was additive. Competitive inhibition assays confirmed that the observed anti-Sm/RNP activity was independent of the rheumatoid factor activity. No cross-reaction was detected from the rheumatoid factor.
Interference Substances
Hemolytic and lipidemic samples. To investigate the performance of the ENA IgG BeadChip Test If it the presence of potential interferents, a hemolytic sample was identified from the normal oyoten in the prooms of processes in the disease samples. These two samples were added at a 1:10 dilution to the pooled positive control. The hemolytic sample did not have significant effect on assay performance, while the lipidemic sample showed apparent interference with the assay, including inhibition of the protein L activity resulting in a chip QC failure. It is recommended that lipidemic samples not be used with the BeadChip.
Additionally, PDP-90 samples were titrated with purified hemoglobin and bilirubin purchased from Auditionally, FBF the operating range of the assay in the presence of these substances. Bilirubin at Oncentrations of 10, 20, and 40 mg/dl and hemoglobin at concentrations of 250, 500, and 1000 mg/dl were not found to interfere with the assay within the tested limits.
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Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three lines representing its body and wings. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.
Public Health Service
MAY 3 1 2005
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
BioArray Solutions, Ltd. c/o Mr. Kevin Wyckoff Quality Assurance & Regulatory Affairs Manager 35 Technology Drive Suite 100 Warren, NJ 07059
Re: K043067
Trade/Device Name: ENA IgG BeadChip™ Test System on the Array Imaging System (AIS 400) Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LLL Dated: November 5, 2004 Received: November 8, 2004
Dear Mr. Wyckoff:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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); good manufacturing practice requirements as set forth in the quality
8
Page 2 - Mr. Kevin Wyckoff
systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (240) 276-0131. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address
http://www.fda.gov/cdrh/dsma/dsmamain.html
Sincerely yours.
Robert L. Beckerf
Robert L. Becker, Jr., M.D., Ph Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE STATEMENT
510(k) Number (if known): K043067
Device Name: ENA IgG BeadChip™ Test System
Indications For Use:
The BioArray Solutions ENA IgG BeadChip™ Test System is intended for use in testing human serum for the presence of human IgG class antibodies to six extractable nuclear antigens, SSA, SSB, Sm, Sm/RNP, Scl-70, and Jo-1. The presence of these autoantibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of systemic lupus erythematosus, Sjögren's syndrome, scleroderma and myositis. This ENA IgG BeadChip is for use with Array Imaging System 400 (AIS400). This test is for in vitro diagnostic use.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
OR
×
(Per 21 CFR 801.109)
Over-The-Counter Use (Optional Format 1-2-96)
Mana M. Khan
Division Sign-Off
Office of In Vitro Dlagnostic Device Evaluation and Sately
510(k) K043067