(232 days)
Not Found
No
The summary describes a standard immunoassay using flow cytometry and mentions software for running the test, but there is no indication of AI or ML being used for data analysis, interpretation, or any other function. The performance studies focus on traditional analytical and comparison metrics.
No
Explanation: The device is explicitly stated to be for "in vitro diagnostic use" and its clinical utility is to "aid in the diagnosis of connective diseases," not to treat or provide therapy.
Yes
The device's 'Intended Use / Indications for Use' explicitly states: "The results of the FIDIS™ CONNECTIVE 10* are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of connective diseases" and "This test is for in vitro diagnostic use." This clearly indicates its role in aiding diagnosis.
No
The device description clearly states that the kit includes physical components such as a microplate, vials of beads, buffers, controls, and other reagents. While software (MLX-BOOSTER™ Software) is mentioned as part of the system, the core of the device is a physical immunoassay kit.
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."
- Nature of the Test: The device is a "semi-quantitative homogeneous fluorescentbased microparticles immunoasay using flow cytometry" used to detect autoantibodies in serum. This is a classic example of an in vitro diagnostic test, as it analyzes biological samples (serum) outside of the body to provide information for diagnosis.
- Clinical Utility: The stated clinical utility is to "aid in the diagnosis of connective diseases." This directly aligns with the purpose of IVD devices, which are used to diagnose, monitor, or treat diseases or conditions.
- Intended User/Care Setting: The "Intended User / Care Setting" is listed as "in vitro diagnostic use," further confirming its classification.
N/A
Intended Use / Indications for Use
The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescentbased microparticles immunoasay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SSA (60 kDa and 52 kDa), SSB, Sm, Sm/RNP, Scl70, Jo1, ribosome and centromere.
(*Antibodies to dsDNA, Sm, Sm/RNP, SSA, SSB, Scl-70, Jo-1, ribosome and centromere can be reported using this assay).
Clinical utility:
The results of the FIDIS™ CONNECTIVE 10* are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of connective diseases (systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective tissue disease (MCTD), scleroderma, dermatomyositis and CREST syndrome).
FIDIS™ CONNECTIVE 10* kit uses serum only, and is to be run on the FIDIS™ Instrument and MLX-BOOSTER™ Software.
FIDIS™ CONNECTIVE 10* kit may be used with the CARIS™ system (diluting and dispensing device).
This test is for in vitro diagnostic use.
Product codes (comma separated list FDA assigned to the subject device)
LLL, LKS, LKO, LKP, LSW, LJM, MQA
Device Description
The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SSA (60kDa and 52kDa), SSB, Sm, Sm/RNP, Scl70, Jo-1, ribosome and centromere. The kit includes a 96-well microplate, vials of color-coded microsphere beads coupled with various antigens and internal standard beads, sample dilution buffer, calibrator, positive control, negative control, anti-human IgG coupled to phycoerythrin, washing buffer, and reconstitution buffer for the microsphere set. It is designed to be run on the FIDIS™ Instrument and MLX-BOOSTER™ Software, and optionally with the CARIS™ system (diluting and dispensing device).
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Comparison with predicate:
The study was performed on 264 samples characterized with the predicate test, with 194 samples positive for one or more parameters and 70 negative samples (including some with potential biological interferences). All equivocal samples with predicate and modified CONNECTIVE 10* assays were considered negative for comparison and evaluation.
Comparison (manual versus automated assay preparation):
The study was performed on 264 samples characterized with the predicate test, with 194 samples positive for one or more parameters and 70 negative samples (including some with potential biological interferences). All equivocal samples with FIDIS™ CONNECTIVE 10* assays were considered negative for the comparison and evaluation studies.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
- Analytical performance:
a. Precision: Assessed in 53 samples.
- Within-run (intra-assay): 6 samples (5 for Jo1) tested 10 times in a same run.
- Between-run (inter-assay): 6 samples (5 for Jo1) tested in 6 runs, 3 times per run.
- Key results: CVs were within acceptance criteria (CV
§ 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
Image /page/0/Picture/0 description: The image shows a logo for Biomedical Diagnostics. The logo consists of the letters "bmd" in a stylized font, with a horizontal line underneath. Below the line, the words "biomedical diagnostics" are written in a smaller, sans-serif font. The letters "bmd" are in a bold, sans-serif font, with the "o" being a perfect circle.
Premarket Notification 510(k) Summary
DEC 1 9 2007
Assigned 510(k) Number: K071210
| 1. Submitted by : | |
|---|---|
| Name: | Biomedical Diagnostics S.A (bmd) |
| Contact Person: | Christelle COURIVAUD |
| Regulatory Affairs Manager | |
| Address: | Actipole 25, 4-6 Bld de Beaubourg |
| 77435 Marne-La-Vallée Cedex 2 | |
| FRANCE | |
| Telephone: | 33 (0)1 64 62 10 12 |
| Fax: | 33 (0)1 64 62 09 66 |
| Establishment | |
| Registration Number: | 3003935253 |
| US Agent correspondent: | |
| Hoppe Regulatory Consultants | |
| Ms P. Ann HOPPE | |
| 2335 Massey Lane | |
| Decatur GA 30033 USA | |
| Phone: 404 248 0002 | |
| E-mail: Hoppe Regulatory@cs.com | |
| 2. Device Name | |
| Trade/Proprietary Name : | FIDIS™ CONNECTIVE 10* assay |
| Common/Usual Name : | MX006 - FIDIS™ CONNECTIVE 10*: Detection test of 10 |
| autoantibody specificities: double stranded DNA (dsDNA), | |
| SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1, | |
| Ribosome and Centromere. | |
| Classification Name: | Antinuclear antibody immunological test system |
| Trade/Proprietary Name : | FIDIS™ Analyzer |
| Classification Name: | Instrumentation for Chemical Multiplex Systems |
| Trade/Proprietary Name : | CARIS™ System |
·
Registered Office : Actipole 25 4-6 bd de Beaubourg 77435 Marne La Vallée cedex 2
1
3. Intended use of the device
The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescentbased microparticles immunoasay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SSA (60 kDa and 52 kDa), SSB, Sm, Sm/RNP, Scl70, Jo1, ribosome and centromere.
(*Antibodies to dsDNA, Sm, Sm/RNP, SSA, SSB, Scl-70, Jo-1, ribosome and centromere can be reported using this assay).
Clinical utility:
The results of the FIDIS™ CONNECTIVE 10* are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of connective diseases (systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective tissue disease (MCTD), scleroderma, dermatomyositis and CREST syndrome).
FIDIS™ CONNECTIVE 10* kit uses serum only, and is to be run on the FIDIS™ Instrument and MLX-BOOSTER™ Software.
FIDIS™ CONNECTIVE 10* kit may be used with the CARIS™ system (diluting and dispensing device).
This test is for in vitro diagnostic use.
4. Materials supplied
| 1 x 96 wells microplate with filtering membrane and a lid. | 1 plate |
|---|---|
| 1 Vial (A) of 10 sets of color-coded microsphere beads coupled with dsDNA, SSA 60 kDa, | |
| SSA 52 kDa, SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes, centromere antigen, plus 1 set | |
| of Internal standard beads. | |
| Lyophilized (to be diluted with the buffer named D) | Sufficient quantity to |
| obtain 6mL after | |
| reconstitution | |
| 1 Vial (B) of sample dilution buffer (white vial) | |
| Ready to use | 2 x 115mL |
| 1 Vial of calibrator titered for the specificities to be mesured | |
| Ready to use | |
| Each titer is printed on the vial label | 1 x 1,5mL |
| 1 Vial of positive control concentrate. This control has a standard reactivity, that provides | |
| evidence of the proper functioning of reagents and correct assay performance. | |
| To be diluted | |
| Expected values are printed on the vial label. | 1 × 250 µL |
| 1 Vial of negative control* concentrate | |
| To be diluted | 1 x 250µL |
2
| 1 Vial of anti-human IgG coupled to phycoerythrin
| Ready to use | 1 x 12mL |
|---|---|
| 1 Vial (C) of washing buffer (black vial) | |
| Ready to use | 1 x 100mL |
| 1 Vial (D) of reconstitution buffer for the microsphere set | |
| Ready to use | 1 x 6mL |
| Package insert | 1 |
| Microplate Assay Configuration Worksheet | 1 |
| Microplate sealing films | 6 |
5. Predicate Device
| 510K Number | Device Classification Name | Manufacturer Name |
|---|---|---|
| K053653 | FIDIST TM CONNECTIVE 10* | bmd |
6. Comparison with the predicate
| | | Predicate Device
FIDIST™ CONNECTIVE 10*
K053653 | | Modified Device
FIDIST™ CONNECTIVE 10* |
|-------------------|----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------|-------------------------------------------------------------|
| Intended use | | Individual determination in human serum of
IgG antibodies against:
dsDNA, SSA 60kDa, SSA 52kDa, SSB,
Sm, Sm/RNP, Scl70, Jo-1, Ribosome and
Centromere | | Same
(minor text changes) |
| CUT-OFF | Negative | 40
for the 10 specificities | | Same |
| Material supplied | | Microplate with caps | | Microplate with sealing films |
| | Beads | Vial of color-coded microsphere set
ready to use (6mL) | | Vial of color-coded microsphere set
Lyophilized (sq 6mL) |
| | Sample dilution | PBS-Tween concentrated | | Sample dilution buffer ready to use |
| Washing buffer | | PBS-Tween concentrated | | Washing buffer ready to use |
| | Internal standard
beads | No | | Yes |
3
| | Predicate Device
FIDIS™ CONNECTIVE 10
K053653 | Modified Device
FIDIS™ CONNECTIVE 10 |
|---------------------------------------|---------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------|
| Assay configuration | 1 "reagent-blank" well
1 "calibrator" well
1 "negative control" well
1 "positive control" well | 1 "reagent-blank" well
1 "negative control" well
1 "positive control" well
2 "calibrator" wells |
| | Diluted sample wells | Same |
| | A second calibrator well every 48 well series | No |
| Incubation time | 2 x 30mn RT | Same |
| Wash step | 2 x 200μL | 2 x 300μL |
| Assay protocol | Optional final wash step | Final wash step (not optional) |
| Software | Booster Version 1.35 | Booster Version 2.2 |
| Detection Method | Fluorescence
(using Luminex 100) | Fluorescence
(using Luminex 200) |
| Sample preparation | Manual preparation | Same |
| Automatic sample preparation (option) | CARIS™ | Same |
7. Performance Characteristics
1. Analytical performance
a. Precision
Precision of the assay was assessed in 53 samples. Precision was determined by calculating the within-run (intra-assay) and the between run (inter-assay).
· For within run: 6 samples (except for Jo1 only 5 samples were tested) 10 times in a same run.
· For between run: 6 samples (except for Jo1 only 5 samples were tested) in 6 runs, 3 times per run.
4
| Sample range | Acceptance
criteria for
within-run
and
between-
run | Within-run
minimal CV%
for the 10
parameters | Within-run
maximal
CV% for the
10 parameters | Between-run
minimal CV%
for the 10
parameters | Between-run
maximal
CV% for the
10 parameters |
|--------------------------------|--------------------------------------------------------------------|-------------------------------------------------------|-------------------------------------------------------|--------------------------------------------------------|--------------------------------------------------------|
| Less than 10
AU/mL or IU/mL | Not
determined | 5.9% | 12.8% | 7.4% | 13.6% |
| 10 to 29 AU/mL
or IU/mL | CV≤20% | 2.5% | 11.8% | 8.2% | 17.3% |
| 29 to 800 AU/mL
or IU/mL | CV≤15% | 2.1% | 12.7% | 4.5% | 14.3% |
Table 1: Summary of FIDIS™ CONNECTIVE 10* precision results
b. Linearity/ assay reportable range
FIDISTM CONNECTIVE 10* assay has been optimized to express the average binding capacity at the current dilution (1/200) by a flow cytometric reading resulting of the median fluorescence value obtained from 200 microspheres per parameter.
Further dilutions potentially give rise to inaccurate results because the reaction conditions and the equilibrium of the immunological reaction would be modified.
c. Interfering Substances
The study was conducted by testing 30 negative samples (for dsDNA, SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1, Ribosome and Centromere) characterized as positive for various potential interferences obtained from routine laboratory (listed in following table).
| Number of positive sample | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| dsDNA | SSA | ||||||||
| 60 kD | SSA | ||||||||
| 52kD | SSB | Sm | Sm/RNP | Scl70 | Jo1 | Ribo | |||
| Cryoglobulinemia N*=2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Complement N*=7 | 2 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 0 |
| IgG monoclonal | |||||||||
| immunoglobulins N*=1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IgM monoclonal | |||||||||
| immunoglobulins N*=5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Rheumatoid factor N*=8 | 1 | 2 | 2 | 1 | 0 | 1 | 0 | 0 | 0 |
| Plasma N*=3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hemolyzed sera N*=3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Anti-smooth muscle | |||||||||
| antibodies N*=1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Table 2: Potential interferences results
*N: number of samples tested
5
d. Threshold values
Threshold values were estimated from the 2 selected populations:
- 50 samples from blood donors -
- 48 samples selected for their potential biological interferences -
The negative thresholds (30AU/mL or 30IU/mL) correspond to the 97.9% for dsDNA. SSA. Sm/RNP: 99.0% for centromere and ribosome, and 100% for SSB, Sm, Scl70 and Jo1 for the populations studied.
e. Stability of the assay results after final wash step
This assay included 3 test series with:
- 5 positive samples for SSA 52kDa, SSA 60kDa, SSB, Sm, Sm/RNP, - Sc170, dsDNA and Centromere;
- 4 positive samples for Jol;
- -3 positive samples for Ribosome.
Each series of tests was washed and read after different times:
- T= 0 hour: the first series of tests was read immediately after the final wash step.
- ﺖ T= 4 hours: the second series of test was read after 4 hours of storage at room temperature away from direct sunlight.
- T=18 hours: the last series was read after 18 hours of storage at room temperature away from direct sunlight.
| %CV acceptance criteria | Parameter | Sample | Mean results Obtained after 18H (AU/mL) | %CV Obtained after 18H | Mean results Obtained after 4H (AU/mL) | %CV Obtained after 4H |
|---|---|---|---|---|---|---|
| %CV ≤ 15% | SSA 52 | Sample 1 | 169 | 9 | Not calculated | Not calculated |
| Sample 2 | 85 | 5 | ||||
| Sample 3 | 52 | 5 | ||||
| Sample 4 | 130 | 5 | ||||
| Sample 5 | 180 | 11 | ||||
| SSA 60 | Sample 6 | 49 | 7 | Not calculated | Not calculated | |
| Sample 7 | 94 | 11 | ||||
| Sample 8 | 68 | 4 | ||||
| Sample 9 | 85 | 7 | ||||
| Sample 10 | 95 | 13 | ||||
| Acceptance criteria | Parameter | Sample | Mean results Obtained after 18H (AU/ml) | %CV Obtained after 18H | Mean results Obtained after 4H (AU/ml) | %CV Obtained after 4H |
| %CV ≤ | ||||||
| 15% | SSB | Sample 11 | 167 | 6 | Not calculated | Not calculated |
| Sample 12 | 59 | 5 | ||||
| Sample 13 | 85 | 7 | ||||
| Sample 14 | 121 | 11 | ||||
| Sm | Sample 15 | 23 | 5 | Not calculated | Not calculated | |
| Sample 16 | 33 | 7 | ||||
| Sample 17 | 309 | 10 | ||||
| Sample 18 | 50 | 7 | ||||
| Sample 19 | 103 | 13 | ||||
| Sample 20 | 147 | 3 | ||||
| Sm/RNP | Sample 21 | 202 | 7 | Not calculated | Not calculated | |
| Sample 22 | 82 | 11 | ||||
| Sample 23 | 374 | 11 | ||||
| Sample 24 | 59 | 9 | ||||
| %CV ≤ | ||||||
| 15% | Scl70 | Sample 25 | 116 | 13 | Not calculated | Not calculated |
| Sample 26 | 57 | 4 | ||||
| Sample 27 | 55 | 5 | ||||
| Sample 28 | 144 | 3 | ||||
| Sample 29 | 308 | 4 | ||||
| Jo1 | Sample 30 | 188 | 7 | Not calculated | Not calculated | |
| Sample 31 | 79 | 13 | ||||
| Jo1 | Sample 32 | 242 | 6 | Not calculated | Not calculated | |
| Sample 33 | 59 | 7 | ||||
| Sample 34 | 77 | 6 | ||||
| Sample 35 | 91 | 16 | ||||
| Centromere | Sample 36 | 82 | 11 | 78 | 11 | |
| Sample 37 | 81 | 7 | 78 | 6 | ||
| Sample 38 | 22 | 9 | 21 | 5 | ||
| Sample 39 | 19 | 5 | 20 | 0 | ||
| Ribosome | Sample 40 | 40 | 13 | Not calculated | Not calculated | |
| Sample 41 | 141 | 7 | ||||
| Sample 42 | 71 | 6 | ||||
| dsDNA | Sample 43 | 49 | 11 | Not calculated | Not calculated | |
| Sample 44 | 123 | 9 | ||||
| Sample 45 | 51 | 10 | ||||
| Sample 46 | 184 | 3 | ||||
| Sample 47 | 62 | 8 |
Table 4: Stability of the assay results after final wash step
6
7
Based on the common laboratories practices, the time range recommended is "one hour for a plate when stored at room temperature away from direct sunlight".
2. Comparison study with predicate
bmd has compared the results obtained with modified FIDIS™ CONNECTIVE 10* versus the results obtained with predicate FIDISTM CONNECTIVE 10* K053653 in manual use.
The study was performed on 264 samples characterized with the predicate test and the result repartition is described as below:
- 194 samples were positive for one or more parameters (see table 5). -
- ー 70 negative samples including some samples evaluated for their potential biological interferences.
| 57 | |
|---|---|
| 48 | |
| 23 | |
| 29 | |
| 40 | |
| 28 | |
| 26 | |
| 26 | |
| 17 | |
| 46 |
Table 5: Number of positive samples per parameter.
FIDIS™ All equivocal samples with predicate and modified CONNECTIVE 10* assays are considered negative for the comparison and the evaluation studies.
| dsDNA | SSA 60kDa | |||||
|---|---|---|---|---|---|---|
| N=116 | Pos | Neg | Total | N=118 | ||
| Pos | 45 | 1 | 46 | Pos | ||
| Neg | 4 | 66 | 70 | Neg | ||
| Total | 49 | 67 | 116 | Total |
Tables 6: Specificity performances
of calculation, these results were considered as negative. Positive percent agreement: 100% (48/48) Negative percent agreement: 98.57% (69/70) Overall agreement: 99.15% (117/118)
Pos
48
0
48
Neg
I
રેજે
70
There were 3 equivocal results with the assay. For purposes There were 2 equivocal results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 91.84% (45/49) Negative percent agreement: 98.51% (66/67) Overall agreement: 95.69% (111/116)
- 2017
Total
49
69
118
8
| SSA 52kDa | |||
|---|---|---|---|
| N=127 | |||
| Pos | Neg | Total | |
| Pos | 58 | 2 | 60 |
| Neg | 3 | 64 | 67 |
| Total | 61 | 66 | 127 |
There were 3 equivocal results with the assay. For purposes of calculation, these results were considered as negative.
Positive percent agreement: 95.08% (58/61) Negative percent agreement: 96.97% (64/66)
Overall agreement: 96.06% (122/127)
| Sm | ||||
|---|---|---|---|---|
| N=99 | Pos | Neg | Total | |
| Pos | 23 | 2 | 25 | |
| Neg | 1 | 73 | 74 | |
| Total | 24 | 75 | 99 |
There were 6 equivocal results with the assay. For purposes of calculation, these results were considered as negative.
Positive percent agreement: 95.83% (23/24) Negative percent agreement: 97.33% (73/75) Overall agreement: 96.97% (96/99)
| Scl70 | ||||
|---|---|---|---|---|
| N=98 | Pos | Neg | Total | |
| Pos | 27 | 2 | 29 | |
| Neg | 1 | 68 | 69 | |
| Total | 28 | 70 | 98 | |
| SS-B | ||||
| N=93 | ||||
| Pos | Neg | Total | ||
| Pos | 23 | 2 | 25 | |
| Neg | 0 | 68 | 68 | |
| Total | 23 | 70 | 93 |
There is 1 equivocal result with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 96.43% (27/28)
Negative percent agreement: 97.14% (68/70) Overall agreement: 96.94% (95/98)
There were I equivocal result with the assay. For purposes of calculation, these results were considered as negative.
Positive percent agreement: 100% (23/23) Negative percent agreement: 97.14% (68/70) Overall agreement: 97.85% (91/93)
| Sm/RNP | |||
|---|---|---|---|
| N= 110 | |||
| Pos | Neg | Total | |
| Pos | 31 | 2 | 33 |
| Neg | 1 | 76 | 77 |
| Total | 32 | 78 | 110 |
There were 7 equivocal results with the assay. For purposes of calculation, these results were considered as negative.
Positive percent agreement: 96.88% (31/32) Negative percent agreement: 97.44% (76/78) Overall agreement: 97.27% (107/110)
| Jo1 | |||
|---|---|---|---|
| N=96 | |||
| Pos | Neg | Total | |
| Pos | 26 | 0 | 26 |
| Neg | 1 | 69 | 70 |
| Total | 27 | 69 | 96 |
There is 0 equivocal result with the assay.
Positive percent agreement: 96.30% (26/27) Negative percent agreement: 100% (69/69) Overall agreement: 98.96% (95/96)
9
| Centromere | ||||
|---|---|---|---|---|
| N=96 | ||||
| Pos | Neg | Total | ||
| Pos | 20 | 0 | 20 | |
| Neg | 4 | 72 | 76 | |
| Total | 24 | 72 | 96 |
| Ribosome | |||||
|---|---|---|---|---|---|
| N=87 | Pos | Neg | Total | ||
| Pos | 18 | 0 | 18 | ||
| Neg | 0 | 69 | 69 | ||
| Total | 18 | 69 | 87 |
There were 7 equivocal results with the assay. For purposes of calculation, these results were considered as negative.
Positive percent agreement: 83.33% (20/24) Negative percent agreement: 100% (72/72)
・
Overall agreement:95.83% (92/96)
There is 1 equivocal result with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (18/18) Negative percent agreement: 100% (69/69) Overall agreement: 100% (87/87)
| Antigenic
Specificity | Sample
number | Positive
percent
agreement
proportion | Negative
percent
agreement
proportion | Overall
agreement
proportion |
|--------------------------|------------------|------------------------------------------------|------------------------------------------------|------------------------------------|
| dsDNA | 116 | 91.84% | 98.51% | 95.69% |
| SSA 60 kDa | 118 | 100% | 98.57% | 99.15% |
| SSA 52 kDa | 127 | 95.08% | 96.97% | 96.06% |
| SSB | 93 | 100% | 97.14% | 97.85% |
| Sm | 99 | 95.83% | 97.33% | 96.97% |
| Sm/RNP | 110 | 96.88% | 97.44% | 97.27% |
| Scl70 | 98 | 96.43% | 97.14% | 96.94% |
| Jo1 | 96 | 96.3% | 100% | 98.96% |
| Centromere | 96 | 83.33% | 100% | 95.83% |
| Ribosome | 87 | 100% | 100% | 100% |
Table 7: Summary of performance agreement results
In addition to the analysis above, the 95% one-sided lower confidence limit in percent of proportion agreement (95% LCL (%) was calculated using the Exact Binomial Test for proportions to determine how low this proportion could be with a 95% confidence.
10
| Antigenic
| Specificity | Positive percent agreement | Negative percent agreement | Overall percent agreement | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N1 | R1 | P1 | ||||||||||
| (%) | 95% | |||||||||||
| LCL (%) | N2 | R2 | P2 | |||||||||
| (%) | 95% | |||||||||||
| LCL (%) | N | R | P | |||||||||
| (%) | 95% | |||||||||||
| LCL (%) | ||||||||||||
| dsDNA | 49 | 45 | 91.84 | 82.29 | 67 | 66 | 98.51 | 93.11 | 116 | 111 | 95.69 | 91.15 |
| SSA 60 kDa | 48 | 48 | 100 | 93.95 | 70 | 69 | 98.57 | 93.40 | 118 | 117 | 99.15 | 96.04 |
| SSA 52 kDa | 61 | 58 | 95.08 | 87.78 | 66 | 64 | 96.97 | 90.77 | 127 | 122 | 96.06 | 91.90 |
| SSB | 23 | 23 | 100 | 87.79 | 70 | 68 | 97.14 | 91.28 | 93 | 91 | 97.85 | 93.39 |
| Sm | 24 | 23 | 95.83 | 81.71 | 75 | 73 | 97.33 | 91.84 | 99 | 96 | 96.97 | 92.35 |
| Sm/RNP | 32 | 31 | 96.88 | 86.02 | 78 | 76 | 97.44 | 92.15 | 110 | 107 | 97.27 | 93.10 |
| Scl70 | 28 | 27 | 96.43 | 84.15 | 70 | 68 | 97.14 | 91.28 | 98 | 95 | 96.94 | 92.28 |
| Jo1 | 27 | 26 | 96.3 | 83.60 | 69 | 69 | 100 | 95.75 | 96 | 95 | 98.96 | 95.15 |
| Centromere | 24 | 20 | 83.33 | 65.82 | 72 | 72 | 100 | 95.92 | 96 | 92 | 95.83 | 90.72 |
| Ribosome | 18 | 18 | 100 | 84.67 | 69 | 69 | 100 | 95.75 | 87 | 87 | 100 | 96.62 |
Table 8: Summary of agreements results - 95% LCL (%)
N1 = No. of positives; R1 = No. of positive agreements; P1 = R1/N1 N2 = No. of negatives; R2 = No. of negative agreements; P2 = R2/N2
N = N1 + N2; R = R1 + R2; P = R/N
All of results show that FIDIS™ CONNECTIVE 10* system can be considered substantially equivalent to the predicate K053653 FIDIS™ CONNECTIVE 10* system.
3. Comparison study with predicate a. Precision
Precision of the assay was assessed in 36 samples. Precision was determined by calculating the within-run (intra-assay) and the between run (inter-assay):
- For within run: 4 samples 10 times in a same run. .
- For between run: 4 samples in 6 runs, 3 times per run. .
| Sample range | Acceptance
criteria for
within-run
and
between-
run | Within-run
minimal CV%
for the 10
parameters | Within-run
maximal
CV% for the
10 parameters | Between-run
minimal CV%
for the 10
parameters | Between-run
maximal
CV% for the
10 parameters |
|--------------------------------|--------------------------------------------------------------------|-------------------------------------------------------|-------------------------------------------------------|--------------------------------------------------------|--------------------------------------------------------|
| Less than 10
AU/mL or IU/mL | Not
determined | Not evaluated | Not evaluated | Not evaluated | Not evaluated |
| 10 to 29 AU/mL
or IU/mL | CV≤20% | 3.8% | 10.3% | 7.3% | 13.9% |
| 29 to 800 AU/mL
or IU/mL | CV≤15% | 1.7% | 10.8% | 3.7% | 12.5% |
| Table 9: Summary of CARISTM Precision results | |||
|---|---|---|---|
11
b. Comparison study (manual versus automated assay preparation steps)
bmd has compared the results obtained with the modified FIDISTM CONNECTIVE 10* for the manual or automated (with CARIS™) assay preparation steps.
The study was performed on 264 samples characterized with the predicate test and the result repartition is described as below:
- 194 samples were positive for one or more parameters (see Table 12) -
- 70 negative samples including some samples evaluated for their potential biological interferences.
| Pathological sample number/parameter | |
|---|---|
| SSA52 | 48 |
| SSA60 | 40 |
| SSB | 22 |
| Sm | 26 |
| Sm/RNP | 33 |
| Scl70 | 27 |
| JOI | 25 |
| Centro | 23 |
| Ribo | 6 |
| dsDNA | 42 |
Table 10: Number of the pathological population per parameter.
All equivocal samples with FIDIS™ CONNECTIVE 10* assays are considered negative for the comparison and the evaluation studies.
| dsDNA
| N=112 | Pos | Neg | Total | |
|---|---|---|---|---|
| Pos | 43 | 0 | ||
| Neg | 0 | 69 | 69 | |
| Total | 43 | 69 | 112 |
Tables 11: Agreement performances
| SSA 60kDa
| N=110 | Pos | Neg | Total | |
|---|---|---|---|---|
| Pos | 42 | 0 | 42 | |
| Neg | 0 | 68 | 68 | |
| Total | 42 | 68 | 110 |
of calculation, these results were considered as negative. Positive percent agreement: 100% (43/43) Negative percent agreement: 100% (69/69) Overall agreement: 100% (112/112)
There were 4 equivocal results with the assay. For purposes There Were 1 equivocal results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (42/42) Negative percent agreement: 100% (68/68) Overall agreement: 100% (110/110)
12
| Pos | Neg | Total | ||
|---|---|---|---|---|
| dsDNA | ||||
| N=112 | Pos | 43 | 0 | 43 |
| Neg | 0 | 69 | 69 | |
| Total | 43 | 69 | 112 |
There were 4 equivocal results with the assay. For purposes of calculation, these results were considered as negative.
Positive percent agreement: 100% (43/43) Negative percent agreement: 100% (69/69) Overall agreement: 100% (112/112)
Tables 11: Agreement performances
SSA 60kDa
N=110
Pos
Neg
| 08 | 110 | |
|---|---|---|
| Positive percent agreement: 100% (42/42) | ||
| Negative percent agreement: 100% (68/68) | There were 1 equivocal results with the assay. For purposes | |
| of calculation, these results were considered as negative. |
Pos
42
0
NUTTS
Total
42
68
Neg
0
68
Overall agreement: 100% (110/110)
| SSA 52kDa
| N=118 | MANUAL | |||
|---|---|---|---|---|
| Pos | Neg | Total | ||
| CARISTY | Pos | 52 | 1 | 53 |
| Neg | 0 | 65 | 65 | |
| Total | 52 | 66 | 118 |
There were 2 equivocal results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (52/52)
Negative percent agreement: 98.48% (65/66)
Overall agreement: 99.15% (117/118)
| Sm | MANUAL | |||
|---|---|---|---|---|
| N=96 | Pos | Neg | Total | |
| CARIST | Pos | 24 | 3 | 27 |
| Neg | 0 | 69 | 69 | |
| Total | 24 | 72 | 96 |
There were 5 equivocal results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (24/24) Negative percent agreement: 95.83% (69/72) Overall agreement: 96.88% (93/96)
| Scl70 | ||||
|---|---|---|---|---|
| N=97 | Pos | Neg | Total | |
| CARIS | Pos | 29 | 0 | 29 |
| Neg | 0 | 68 | 68 | |
| Total | 29 | 68 | 97 |
There is 0 equivocal result with the assay. Positive percent agreement: 100% (29/29) Negative percent agreement: 100% (68/68) Overall agreement: 100% (97/97)
| SSB
| N=92 | MANUAL | |||
|---|---|---|---|---|
| Pos | Neg | Total | ||
| Pos | 25 | 0 | 25 | |
| CARIST | Neg | 0 | 67 | 67 |
| Total | 25 | 67 | 92 |
There is 1 equivocal result with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (25/25) Negative percent agreement: 100% (67/67) Overall agreement: 100% (92/92)
| Sm/RNP | ||||
|---|---|---|---|---|
| N=103 | MANUAL | |||
| Pos | Neg | Total | ||
| CARIS | Pos | 32 | 3 | 35 |
| Neg | 0 | 68 | 68 | |
| Total | 32 | 71 | 103 |
There were 6 borderline results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (32/32) Negative percent agreement: 95.77% (68/71) Overall agreement: 97.09% (100/103)
| Jo1
| N=95 | MANUAL | ||||
|---|---|---|---|---|---|
| Pos | Neg | Total | |||
| CARIST | Pos | 26 | 0 | 26 | |
| Neg | 0 | 69 | 69 | ||
| Total | 26 | 69 | 95 |
There is 0 equivocal result with the assay. Positive percent agreement: 100% (26/26) Negative percent agreement: 100% (69/69) Overall agreement: 100% (95/95)
13
| Centromere | MANUAL | ||||
|---|---|---|---|---|---|
| N=93 | Pos | Neg | Total | ||
| Pos | 20 | 4 | 24 | ||
| Neg | 0 | 69 | 69 | ||
| Total | 20 | 73 | 93 |
| Ribosome | MANUAL | |||
|---|---|---|---|---|
| N=76 | Pos | Neg | Total | |
| CARIS | Pos | 8 | 0 | 8 |
| Neg | 0 | 68 | 68 | |
| Total | 8 | 68 | 76 |
There were 6 equivocal results with the assay. For purpose There is 0 equivocal result with the assay. of calculation, these results were considered as negative.
Positive percent agreement: 100% (20/20)
Negative percent agreement: 94.52% (69/73)
Overall agreement: 95.70% (89/93)
e There is 0 equivocal result with the assay.
Positive percent agreement: 100% (8/8) Negative percent agreement: 100% (68/68) Overall agreement: 100% (76/76)
| Antigenic
Specificity | Sample
number | Positive
percent
agreement | Negative
percent
agreement | Overall
agreement |
|--------------------------|------------------|----------------------------------|----------------------------------|----------------------|
| | | proportion | proportion | proportion |
| dsDNA | 112 | 100% | 100% | 100% |
| SSA 60 kDa | 110 | 100% | 100% | 100% |
| SSA 52 kDa | 118 | 100% | 98.48% | 98.48% |
| SSB | 92 | 100% | 100% | 100% |
| Sm | 96 | 100% | 95.83% | 95.83% |
| Sm/RNP | 13 | 100% | 95.77% | 95.77% |
| Scl70 | 97 | 100% | 100% | 100% |
| Jo1 | 95 | 100% | 100% | 100% |
| Centromere | 93 | 100% | 94.52% | 94.52% |
| Ribosome | 76 | 100% | 100% | 100% |
Table 12: Summary of performance agreement results
14
In addition to the analysis above, the 95% one-sided lower confidence limit in percent of proportion agreement (95% LCL (%) was calculated using the Exact Binomial Test for proportions to determine how low this proportion could be with a 95% confidence.
| Antigenic
| Specificity | Positive percent agreement | Negative percent agreement | Overall percent agreement | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N₁ | R₁ | P₁ | ||||||||||
| (%) | 95% LCL (%) | N₂ | R₂ | P₂ | ||||||||
| (%) | 95% LCL (%) | N | R | P | ||||||||
| (%) | 95% LCL (%) | |||||||||||
| dsDNA | 43 | 43 | 100 | 93.27 | 69 | 69 | 100 | 95.75 | 112 | 112 | 100 | 97.36 |
| SSA 60 kDa | 42 | 42 | 100 | 93.12 | 68 | 68 | 100 | 95.69 | 110 | 110 | 100 | 97.31 |
| SSA 52 kDa | 52 | 52 | 100 | 94.40 | 66 | 65 | 98.48 | 93.01 | 118 | 117 | 99.15 | 96.04 |
| SSB | 25 | 25 | 100 | 88.71 | 67 | 67 | 100 | 95.63 | 92 | 92 | 100 | 96.80 |
| Sm | 24 | 24 | 100 | 88.27 | 72 | 69 | 95.83 | 89.58 | 96 | 93 | 96.88 | 92.12 |
| Sm/RNP | 32 | 32 | 100 | 91.06 | 71 | 68 | 95.77 | 89.44 | 103 | 100 | 97.09 | 92.64 |
| Scl70 | 29 | 29 | 100 | 90.19 | 68 | 68 | 100 | 95.69 | 97 | 97 | 100 | 96.96 |
| Jo1 | 26 | 26 | 100 | 89.12 | 69 | 69 | 100 | 95.75 | 95 | 95 | 100 | 96.90 |
| Centromere | 20 | 20 | 100 | 86.09 | 73 | 69 | 94.52 | 87.90 | 93 | 89 | 95.70 | 90.43 |
| Ribosome | 8 | 8 | 100 | 68.77 | 68 | 68 | 100 | 95.69 | 76 | 76 | 100 | 96.13 |
Table 13: Summary of performance agreements results - 95% LCL (%)
N1 = No. of positives; R1 = No. of positive agreements; P1 = R1/N1 N2 = No. of negatives; R2 = No. of negative agreements; P2 = R2/N2 N = N; + N2; R = R1 + R2; P = R/N
All previous evaluation results indicate that manual and automated (with CARIS™) assay preparation steps are considered substantially equivalents.
8. Conclusions
In conclusion, all supporting data demonstrate that the FIDIS™ CONNECTIVE 10* system can be considered substantially equivalent to the predicate device.
15
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/15/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized eagle or bird in flight.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
DEC 1 9 2007
Biomedical Diagnostics S.A. (BMD) c/o Ms. Christelle Courivaud Regulatory Affairs Manager Actipole 25. 4-6 Bld de Beaubourg 77435 Marne La Vallée cedex 2 France
Re: K071210
Trade/Device Name: FIDISTM CONNECTIVE 10* Assay Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LLL, LKS, LKO, LKP, LSW, LJM, MQA Dated: December 5, 2007 Received: December 7, 2007
Dear Ms. Courivaud:
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 systems (QS) regulation (21 CFR Part 820). This letter will allow you to
16
Page 2 -
begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Robert D. Becker
Robert L. Becker, Jr., M.D., Ph.Ø Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure -
17
Indication for Use
510(k) Number (if known): K071210
Device Name:
FIDISTM CONNECTIVE 10*
Indication For Use:
The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry. The test system is used to simulaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNAA), SSA (60 kDa and 52 kDa), SSB, Sm, Sm/RNP, Scl70, Jo1, ribosome and centromere,
(*Antibodies to dsDNA, Sm, Sm/RNP, SSA, SSB, Scl-70, Jo-1, ribosome and centromere can be reported using this assay).
Clinical utility:
The results of the FIDIS™ CONNECTIVE 10* are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of connective diseases (systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective disease (MCTD), scleroderma, dermatomyositis and CREST syndrome).
FIDIS™ CONNECTIVE 10* kit uses serum only, and is to be run on the FIDIS™ Instrument and MLX-BOOSTER™ Software.
FIDIS™ CONNECTIVE 10* kit may be used with the CARIS™ system (diluting and dispensing device).
This test is for in vitro diagnostic use.
Prescription Use __ X (21 CFR Part 801 Subpart D)
And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Maria M Elan
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety