VIDAS D-DIMER EXCLUSION II (DEX2)

K112818 · bioMerieux, Inc. · DAP · Jul 31, 2012 · Hematology

Device Facts

• Record ID: K112818
• Device Name: VIDAS D-DIMER EXCLUSION II (DEX2)
• Applicant: bioMerieux, Inc.
• Product Code: DAP · Hematology
• Decision Date: Jul 31, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7320
• Device Class: Class 2

Intended Use

VIDAS® D-Dimer Exclusion II™ is an automated quantitative test for use on the instruments of the VIDAS family for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate, CTAD) using the ELFA technique (Enzyme Linked Fluorescent Assay). VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

Device Story

VIDAS® D-Dimer Exclusion II is an automated, quantitative in vitro diagnostic assay for measuring fibrin degradation products (FbDP) in human plasma. The device utilizes the Enzyme-Linked Fluorescent Assay (ELFA) technique on VIDAS family instruments. Operation involves a two-step sandwich immunoassay: sample is drawn into a Solid Phase Receptacle (SPR) coated with anti-FbDP antibodies; antigen binds to the SPR; unbound components are washed away. A conjugate containing alkaline phosphatase-labeled anti-FbDP monoclonal antibody is added to form a sandwich. After further washing, a substrate (4-Methyl-umbelliferyl phosphate) is introduced; the enzyme catalyzes its conversion to a fluorescent product (4-Methyl-umbelliferone). Fluorescence intensity, measured at 450 nm, is proportional to antigen concentration. The instrument automatically calculates results against a stored calibration curve. Used in clinical laboratories, the assay provides quantitative results to clinicians to help rule out DVT or PE in suspected outpatients, potentially reducing the need for further diagnostic imaging.

Clinical Evidence

Clinical evaluation used 315 banked, frozen plasma samples from patients suspected of VTE. Sensitivity was 100% (95% CI: 95.1%-100%) and specificity was 35.7% (95% CI: 29.6%-42.1%) at the 500 ng/mL FEU cut-off. NPV was 100% (95% CI: 95.8%-100%). Comparison with predicate device showed high concordance. Bench testing included precision (CV <7%), linearity (45-10,000 ng/mL), and interference studies (hemoglobin, lipids, bilirubin, albumin, and 47 drugs).

Technological Characteristics

ELFA-based immunoassay. Materials: polypropylene reagent strips, SPR coated with mouse anti-D-Dimer monoclonal antibody. Energy: optical (fluorescence measurement at 450 nm). Connectivity: standalone instrument (VIDAS/miniVIDAS). Calibration: Master Lot Entry (MLE) barcode. Standards: CLSI EP5-A2, EP6-A, EP7-A, EP9-A2, EP12-A2, EP17-A.

Indications for Use

Indicated for outpatients suspected of deep vein thrombosis (DVT) or pulmonary embolism (PE) to exclude disease when used in conjunction with a clinical pretest probability assessment model.

Predicate Devices

• VIDAS® D-dimer Exclusion Assay (k040882)

Submission Summary (Full Text)

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K112818

JUL 3 1 2012

VIDAS® D-Dimer Exclusion II Assay

Traditional 510(k) Submission

Image /page/0/Picture/4 description: The image shows the logo for bioMérieux. The logo consists of a circle that is divided into two halves, with the left half having horizontal lines and the right half being solid black. The text "BIOMÉRIEUX" is written in all caps below the circle.

510(k) Summary

July 12, 2012

# 510(k) SUMMARY

# VIDAS® D-Dimer Exclusion II Assay

## A. Submitter Information

Submitter's Name: bioMérieux, Inc.

| II. | Address: | 595 Anglum Road<br>Hazelwood, MO 63042 |
|-----|-------------------------------|----------------------------------------------------------------------------------|
| | Contact Person: | John Albright |
| | Phone Number: | 314-731-8546 |
| | Fax Number: | 314-731-8689 |
| | Date of Preparation: | September 2011 |
| | B. Device Name<br>Trade Name: | VIDAS® D-Dimer Exclusion II Assay |
| | Common Name: | D-Dimer Exclusion II Assay |
| | Classification Name: | 21 CFR 864.7320 Product Code DAP<br>Fibrinogen/fibrin degradation products assay |

#### C. Predicate Device Name Trade Name:

VIDAS® D-Dimer Exclusion Assay

## D. Device Description

The VIDAS® D-Dimer Exclusion II assay is an automated quantitative test for use on the instruments of the VIDAS family for the determination of fibrin degradation products (FbDP) in human plasma (sodium citrate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

The assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. The assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). The individual kit components are described in detail on the following pages.

All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times.

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BIME REETIX

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Traditional 510(k) Submission

510(k) Summarv

First, the sample is taken by the SPR, diluted and then cycled in and out of the SPR several times. The antigen binds to the anti-FbDP immunodobulins coated on the SPR. Unbound components are eliminated during a washing step. In the second step, the conjugate that contains an alkaline phosphatase labeled anti-FbDP monoclonal antibody is cvcled in and out of the SPR to form a sandwich. Unbound components are eliminated during the washing steps.

A detection step is then performed. The substrate (4-Methyl-umbellifery) phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone), the fluorescence of which is measured at 450 nm. The intensity of fluorescence is proportional to the concentration of antigen present in the sample. At the end of the assay, results are automatically calculated by the instrument in relation to the calibration curve stored in memory. The results are then printed.

#### E. Intended Use

VIDAS® D-Dimer Exclusion II™ is an automated quantitative test for use on the instruments of the VIDAS family for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate, CTAD) using the ELFA technique (Enzyme Linked Fluorescent Assay). VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical probability assessment model to exclude deep yein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

### F. Technological Characteristics Summary

A general comparison of the similarities and differences of the current assay, VIDAS D-Dimer Exclusion II (ref. 30445) and the predicate assay VIDAS D-Dimer Exclusion (K040882) ref. 30442 is presented in the table below.

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Image /page/2/Picture/0 description: The image shows the logo for bioMerieux. The logo consists of a circle that is half black and half white with vertical lines. The text "BIO M É RIE U X" is below the circle.

## Traditional 510(k) Submission

## 510(k) Summary

| III.<br>Item | VIDAS® D-Dimer Exclusion II Assay | VIDAS® D-Dimer Exclusion Assay<br>(K040882) - Predicate | |
|--------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------|
| General Comparison | | | |
| Intended Use | VIDAS® D-Dimer Exclusion II™ is an<br>automated quantitative test for use on<br>the instruments of the VIDAS family for<br>the immunoenzymatic determination of<br>fibrin degradation products (FbDP) in<br>human plasma (sodium citrate) using<br>the ELFA technique (Enzyme Linked<br>Fluorescent Assay). VIDAS D-Dimer<br>Exclusion II is indicated for use in<br>conjunction with a clinical pretest<br>probability assessment model to<br>exclude deep vein thrombosis (DVT)<br>and pulmonary embolism (PE) disease<br>in outpatients suspected of DVT or PE. | VIDAS D-Dimer Exclusion is an<br>automated quantitative test for use on<br>the VIDAS instruments for the<br>Immunoenzymatic determination of<br>fibrin degradation products (FbDP) in<br>human plasma (sodium citrate) using<br>the ELFA technique (Enzyme-Linked<br>Fluorescent Assay). VIDAS D-Dimer<br>Exclusion is indicated for use in<br>conjunction with a clinical pretest<br>probability assessment model to<br>exclude deep vein thrombosis (DVT)<br>and pulmonary embolism (PE)<br>disease in outpatients suspected of<br>DVT or PE. | |
| Assay Technique | Enzyme-linked fluorescent assay<br>(ELFA) | Enzyme-linked fluorescent assay<br>(ELFA) | |
| Automated | Yes | Yes | |
| Assay Duration | 19 minutes, 57 seconds | 35 minutes, 35 seconds | |
| SPR | Coating solution includes Anti-FbDP<br>monoclonal mouse antibodies<br>No preservative | Coating solution includes Anti-FbDP<br>monoclonal mouse antibodies<br>Buffer preservative=azide | |
| Strip | Conjugate includes alkaline<br>phosphatase-labeled anti-FbDP<br>monoclonal immunoglobulins (mouse)<br>MIT or MIT + BND (Wells 5-9 replaced<br>sodium azide with MIT or MIT+ BND).<br>Sodium azide only remains in well 10.<br>Conjugate buffer contains<br>Non specific Purified mouse IgG*<br>Nonirradiated de-complemented horse | Conjugate includes alkaline<br>phosphatase-labeled anti-FbDP<br>monoclonal immunoglobulins (mouse)<br>Preservative = azide (Wells 5-10<br>contain sodium.azide as the<br>preservative)<br>Conjugate buffer contains<br>Non specific Mouse ascite Tg180<br>Conjugate buffer includes de-<br>complimented irradiated or non | |
| Calibrators and<br>Controls<br>Approximate<br>target (ng/mL) | serum<br>S1: 3000-3500<br>S2=N/A<br>C1 : 5200-6040<br>C2 : 250-380<br>Allows reconstitution with water | irradiated horse serum<br>S1 : 3700-4400<br>S2 : 420-580<br>C1 : 4200-4800<br>C2 : 380-520<br>Reconstituted with the R1 diluent<br>included in the kit | |
| | Recalibration frequency=28 days | Recalibration frequency=14 days | |
| Sample type | Citrated or CTAD plasma | Citrated plasma | |
| Analytical Performance Comparison | | | |
| IV. | Item | VIDAS® D-Dimer Exclusion II Assay | VIDAS® D-Dimer Exclusion Assay (K040882) - Predicate |
| | Assay range | 45-10,000 ng/mL | 45-10,000 ng/mL |
| | Clinical Cut Off | 500 ng/mL | 500 ng/mL |
| | Linearity | 45-10,000 ng/mL | 45-5,000 ng/mL |
| | Detection Limit | ≤ 45 ng/mL | ≤ 45 ng/mL |
| | Hook Effect | 400,000 ng/mL | 400,000 ng/mL |
| Specificity | Fibrinogen (<10 g/L) | No cross reactivity | |
| | Fibrinogen degradation products X (<10 µg/mL) | | No cross reactivity for fibrinogen or fibrinogen degradation products X, Y and D |
| | Fibrinogen degradation products Y (<10 µg/mL ) | | |
| | Fibrinogen degradation products D (10 - 100 µg/mL) | Cross reactivity between 10-100 µg/mL; however such high levels of fibrinogen degradation products D do not occur in the target population of suspected VTE patients | |
| Total Precision (CV) | | CV 6.6 % at 277.97 ng/mL<br>CV 5.9 % at 544.14 ng/mL<br>CV 6.0% at 7,788.88 ng/mL | CV 5.7 % at 264 ng/mL<br>CV 5.8% at 549 ng/mL<br>CV 7.1% at 7283 ng/mL |
| Interference | | No interference with<br>Hemoglobin up to 300 µmol/L<br>Lipemia up to 30 g/L<br>Bilirubinemia up to 537 µmol/L<br>Rheumatoid factor: up to 400 IU/mL<br>Human albumin: up to 60 g/L | No interference with<br>Hemoglobin up to 300µmol/L<br>Lipemia up to 20 g/L<br>Bilirubin up to 537µmol/L<br>Rheumatoid 396 IU/mL |
| Drug Interference | | 47 analytes were tested and no interference was observed | Not performed |
| Normal Values | | 90% less than 500 ng/mL | 96% less than 500 ng/mL |
| Method Comparison | | D-Dimer Exclusion (K040882) vs. D-Dimer Exclusion II | N/A |

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Image /page/3/Picture/1 description: The image shows the logo for bioMérieux. The logo consists of a circle that is half black and half striped, with the company name "BIOMÉRIEUX" written below it. A thin, curved line runs vertically through the center of the circle and the company name.

Traditional 510(k) Submission

510(k) Summary

## G. Performance Data

A summary of the non-clinical results is presented in the table below.

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Traditional 510(k) Submission

### H. Conclusion

## The VIDAS® D-Dimer Exclusion II Assay is substantially equivalent to the bioMerieux VIDAS D-Dimer Exclusion Assay.

The 510(k) summary includes only information that is also covered in the body of the 510(k). The summary does not contain any puffery or unsubstantiated labeling claims. The summary does not contain any raw data, i.e., contains only summary data. The summary does not contain any trade secret or confidential commercial information. The summary does not contain any patient identification information.

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10903 New Hampshire Avenue Silver Spring, MD 20993

bioMerieux, Inc. c/o Ms. VeRonica Daenzer Sr. Regulatory Affairs Specialist 595 Anglum Road Hazelwood, MO 63042-2320

JUL 3 1 2012

Re: k112818

Trade/Device Name: VIDAS® D-Dimer Exclusion IITM (DEX2) Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/fibrin degradation products assay Regulatory Class: Class II Product Code: DAP Dated: July 30, 2012 Received: July 31, 2012

Dear Ms Daenzer:

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 class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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

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Page 2 - Ms. VeRonica Daenzer

comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 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 advice for your device on our labeling regulation (21 CFR Parts 801 and 809), 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 the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Reena Philip

on Maria M. Chan, Ph.D. 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

510(k) Number (if known):___K112818

Device Name: VIDAS® D-Dimer Exclusion II Assay

Indications For Use:

VIDAS® D-Dimer Exclusion II™ is an automated quantitative test for use on the instruments of the VIDAS family for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate, CTAD) using the ELFA technique (Enzyme Linked Fluorescent Assay). VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In-Vitro Diagnostic Device Evaluation and Safety

510(k) K112818

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