MODIFICATION TO FIDIS CONNECTIVE 10*, MODEL MX006

K071210 · Biomedical Diagnostics (Bmd) SA · LKO · Dec 19, 2007 · Immunology

Device Facts

• Record ID: K071210
• Device Name: MODIFICATION TO FIDIS CONNECTIVE 10*, MODEL MX006
• Applicant: Biomedical Diagnostics (Bmd) SA
• Product Code: LKO · Immunology
• Decision Date: Dec 19, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5100
• Device Class: Class 2

Intended Use

The FIDIS™ Connective 10* kit is a fluorescent immunoassay for the semi-quantitative simultaneous detection of 10 autoantibody specificities directed against double stranded DNA (dsDNA), SSA (60 kDA and 52 kDA), SSB, Sm, Sm/RNP, Scl-70, Jo-1 ribosome and centromere in human serum. (*Antibodies to dsDNA, SSA, SSB, Sm, Sm/RNP, Scl-70, Jo-1, ribosome and centromere can be reported using this assay).

Device Story

Multiplex bead-based flow cytometric immunoassay; detects 10 autoantibody specificities in human serum. Input: serum samples; antigen-coupled color-coded microspheres; goat anti-human IgG phycoerythrin conjugate. Operation: microspheres mixed with serum; flow cytometer uses red laser to identify microsphere set (analyte) and green laser to quantify bound IgG fluorescence. Output: semi-quantitative results for 10 autoantibodies. Used in clinical laboratories; processed via FIDIS instrument (Luminex 200 platform) with MLX-Booster 2.2 software; optional CARIS system for automated dilution/dispensing. Results assist clinicians in diagnosing systemic autoimmune diseases.

Clinical Evidence

Bench testing only. Precision/reproducibility evaluated with four samples across reportable range (within-run CVs 2.1-12.7%; between-run CVs 4.5-14.6%). Method comparison (N=264) between modified and initial FIDIS device showed high positive/negative agreement (overall agreement 95.69-100% across parameters). Comparison between manual and automated CARIS system also performed, showing high agreement. No clinical sensitivity/specificity data provided.

Technological Characteristics

Multiplexed flow cytometry immunoassay. Components: color-coded microsphere beads, anti-human IgG-phycoerythrin conjugate, buffers. Energy source: laser-based flow cytometry (Luminex 200). Connectivity: standalone instrument with MLX-BOOSTER™ software. Software: MLX-BOOSTER™ version 2.2. Form factor: 96-well microplate assay.

Indications for Use

Indicated for the semi-quantitative detection of 10 autoantibody specificities (dsDNA, SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1, ribosome, centromere) in human serum to aid in the diagnosis of connective tissue diseases including SLE, Sjogren's syndrome, MCTD, scleroderma, dermatomyositis, and CREST syndrome. For prescription use only.

Regulatory Classification

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).

Predicate Devices

• FIDISTM Connective 10* (k053653)

Submission Summary (Full Text)

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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: [phone] |
| | E-mail: Hoppe [e-mail] |
| 2. Device Name | |
| Trade/Proprietary Name : | FIDIS™ CONNECTIVE 10* assay |
| Common/Usual Name : | MX006 - FIDIS™ CONNECTIVE 10*: Detection test of 10<br>autoantibody specificities: double stranded DNA (dsDNA),<br>SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1,<br>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

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### 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,<br>SSA 52 kDa, SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes, centromere antigen, plus 1 set<br>of Internal standard beads.<br>Lyophilized (to be diluted with the buffer named D) | Sufficient quantity to<br>obtain 6mL after<br>reconstitution |
| 1 Vial (B) of sample dilution buffer (white vial)<br>Ready to use | 2 x 115mL |
| 1 Vial of calibrator titered for the specificities to be mesured<br>Ready to use<br>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<br>evidence of the proper functioning of reagents and correct assay performance.<br>To be diluted<br>Expected values are printed on the vial label. | 1 × 250 µL |
| 1 Vial of negative control* concentrate<br>To be diluted | 1 x 250µL |

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| 1 Vial of anti-human IgG coupled to phycoerythrin<br>Ready to use | 1 x 12mL |
|-----------------------------------------------------------------------------|-----------|
| 1 Vial (C) of washing buffer (black vial)<br>Ready to use | 1 x 100mL |
| 1 Vial (D) of reconstitution buffer for the microsphere set<br>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<br>FIDIST™ CONNECTIVE 10*<br>K053653 | | Modified Device<br>FIDIST™ CONNECTIVE 10* |
|-------------------|----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------|-------------------------------------------------------------|
| Intended use | | Individual determination in human serum of<br>IgG antibodies against:<br>dsDNA, SSA 60kDa, SSA 52kDa, SSB,<br>Sm, Sm/RNP, Scl70, Jo-1, Ribosome and<br>Centromere | | Same<br>(minor text changes) |
| CUT-OFF | Negative | <30<br>for the 10 specificities | - In IU/mL for<br>dsDNA<br>- In AU/mL for<br>the 9 other<br>specificities | Same |
| | Equivocal | 30-40<br>for the 10 specificities | | Same |
| | Positive | >40<br>for the 10 specificities | | Same |
| Material supplied | | Microplate with caps | | Microplate with sealing films |
| | Beads | Vial of color-coded microsphere set<br>ready to use (6mL) | | Vial of color-coded microsphere set<br>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<br>beads | No | | Yes |

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| | Predicate Device<br>FIDIS™ CONNECTIVE 10<br>K053653 | Modified Device<br>FIDIS™ CONNECTIVE 10 |
|---------------------------------------|---------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------|
| Assay configuration | 1 "reagent-blank" well<br>1 "calibrator" well<br>1 "negative control" well<br>1 "positive control" well | 1 "reagent-blank" well<br>1 "negative control" well<br>1 "positive control" well<br>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<br>(using Luminex 100) | Fluorescence<br>(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.

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| Sample range | Acceptance<br>criteria for<br>within-run<br>and<br>between-<br>run | Within-run<br>minimal CV%<br>for the 10<br>parameters | Within-run<br>maximal<br>CV% for the<br>10 parameters | Between-run<br>minimal CV%<br>for the 10<br>parameters | Between-run<br>maximal<br>CV% for the<br>10 parameters |
|--------------------------------|--------------------------------------------------------------------|-------------------------------------------------------|-------------------------------------------------------|--------------------------------------------------------|--------------------------------------------------------|
| Less than 10<br>AU/mL or IU/mL | Not<br>determined | 5.9% | 12.8% | 7.4% | 13.6% |
| 10 to 29 AU/mL<br>or IU/mL | CV≤20% | 2.5% | 11.8% | 8.2% | 17.3% |
| 29 to 800 AU/mL<br>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<br>60 kD | SSA<br>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<br>immunoglobulins N*=1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| IgM monoclonal<br>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<br>antibodies N*=1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |

Table 2: Potential interferences results

*N: number of samples tested

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#### 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 ≤<br>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 ≤<br>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

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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

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| 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)

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| 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<br>Specificity | Sample<br>number | Positive<br>percent<br>agreement<br>proportion | Negative<br>percent<br>agreement<br>proportion | Overall<br>agreement<br>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.

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| Antigenic<br>Specificity | Positive percent agreement | | | | Negative percent agreement | | | | Overall percent agreement | | | |
|--------------------------|----------------------------|----|-----------|----------------|----------------------------|----|-----------|----------------|---------------------------|-----|----------|----------------|
| | N1 | R1 | P1<br>(%) | 95%<br>LCL (%) | N2 | R2 | P2<br>(%) | 95%<br>LCL (%) | N | R | P<br>(%) | 95%<br>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<br>criteria for<br>within-run<br>and<br>between-<br>run | Within-run<br>minimal CV%<br>for the 10<br>parameters | Within-run<br>maximal<br>CV% for the<br>10 parameters | Between-run<br>minimal CV%<br>for the 10<br>parameters | Between-run<br>maximal<br>CV% for the<br>10 parameters |
|--------------------------------|--------------------------------------------------------------------|-------------------------------------------------------|-------------------------------------------------------|--------------------------------------------------------|--------------------------------------------------------|
| Less than 10<br>AU/mL or IU/mL | Not<br>determined | Not evaluated | Not evaluated | Not evaluated | Not evaluated |
| 10 to 29 AU/mL<br>or IU/mL | CV≤20% | 3.8% | 10.3% | 7.3% | 13.9% |
| 29 to 800 AU/mL<br>or IU/mL | CV≤15% | 1.7% | 10.8% | 3.7% | 12.5% |

| Table 9: Summary of CARISTM Precision results | | | |
|-----------------------------------------------|--|--|--|
| | | | |

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#### 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<br>N=112 | | Pos | Neg | Total |
|----------------|-------|-----|-----|-------|
| | | Pos | 43 | 0 |
| | Neg | 0 | 69 | 69 |
| | Total | 43 | 69 | 112 |

#### Tables 11: Agreement performances

| SSA 60kDa<br>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)

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| | | Pos | Neg | Total |
|----------------|-------|-----|-----|-------|
| dsDNA<br>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)<br>Negative percent agreement: 100% (68/68) | There were 1 equivocal results with the assay. For purposes<br>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<br>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<br>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<br>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)

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| 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<br>Specificity | Sample<br>number | Positive<br>percent<br>agreement | Negative<br>percent<br>agreement | Overall<br>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

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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<br>Specificity | Positive percent agreement | | | Negative percent agreement | | | Overall percent agreement | | | | | |
|--------------------------|----------------------------|----|-----------|----------------------------|----|----|---------------------------|-------------|-----|-----|----------|-------------|
| | N₁ | R₁ | P₁<br>(%) | 95% LCL (%) | N₂ | R₂ | P₂<br>(%) | 95% LCL (%) | N | R | P<br>(%) | 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.

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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 [phone]. 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 [phone] or [phone] 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 -

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# 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