HEMOSIL D-DIMER HS

K070927 · Instrumentation Laboratory CO · DAP · Sep 17, 2007 · Hematology

Device Facts

• Record ID: K070927
• Device Name: HEMOSIL D-DIMER HS
• Applicant: Instrumentation Laboratory CO
• Product Code: DAP · Hematology
• Decision Date: Sep 17, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7320
• Device Class: Class 2

Intended Use

HemosIL D-Dimer HS is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude venous thromboembolism (VTE) in outpatients suspected of deep venous thrombosis (DVT) and pulmonary embolism (PE). For in vitro diagnostic use.

Device Story

Automated latex-enhanced turbidimetric immunoassay for quantitative D-Dimer measurement in human citrated plasma. Input: patient citrated plasma sample. Mechanism: polystyrene latex particles coated with F(ab)2 fragments of monoclonal anti-D-Dimer antibody; agglutination occurs in presence of D-Dimer; degree of agglutination measured via decrease in transmitted light (turbidimetry). Output: quantitative D-Dimer concentration. Used in clinical laboratory settings on ACL TOP instrumentation. Results interpreted by clinicians alongside PTP assessment models (e.g., Wells model) to rule out DVT/PE in suspected outpatients. Enables exclusion of VTE, potentially reducing need for further diagnostic imaging.

Clinical Evidence

Multi-center study (n=668) of emergency unit patients suspected of DVT (n=307) or PE (n=361). Patients assessed via Wells PTP model. Negative D-Dimer results combined with low/moderate PTP used to exclude VTE. Sensitivity for DVT and PE was 100% (95% CI: 94.2-100% and 93.8-100% respectively). NPV was 100% for both conditions. Specificity was 38.4% for DVT and 35.6% for PE. No patients with negative D-Dimer results developed DVT or PE during 3-month follow-up.

Technological Characteristics

Latex-enhanced turbidimetric immunoassay. Reagents: polystyrene latex particles coated with F(ab)2 fragments of monoclonal anti-D-Dimer antibody. Instrumentation: ACL TOP. Sample type: citrated plasma. Measuring range: 150-69000 ng/mL. Detection limit: 21 ng/mL. Clinical cut-off: 230 ng/mL.

Indications for Use

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

Predicate Devices

• Biomerieux Vidas® D-Dimer Exclusion Assay (K040882)
• HemosIL D-Dimer HS (K050544)

Submission Summary (Full Text)

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K070927

# HemosIL D-Dimer HS 510(k) Summary (Summary of Safety and Effectiveness)

#### Applicant Contact Information:

| Applicant: | Instrumentation Laboratory Co. | |
|-------------------|-------------------------------------------|-------------|
| Address: | 113 Hartwell Avenue | |
| | Lexington, MA 02421 | SEP 17 2007 |
| Contact Person: | Carol Marble, Regulatory Affairs Director | |
| Phone Number: | 781-861-4467 | |
| Fax Number: | 781-861-4207 | |
| Preparation Date: | August 13, 2007 | |

#### Device Trade Name:

HemosIL D-Dimer HS

### Regulatory Information:

| Classification Name: | Fibrinogen and Fibrin Split Products, Antigen, Antiserum, Control |
|----------------------|-------------------------------------------------------------------|
| Device Class: | Class II |
| Regulation No.: | 864.7320 |
| Product Code: | DAP |
| Panel: | Hematology |

## Predicate Device:

K040882

Biomerieux Vidas® D-Dimer Exclusion Assay

### Device Intended Use:

HemosIL D-Dimer HS is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude venous thromboembolism (VTE) in outpatients suspected of deep venous thrombosis (DVT) and pulmonary embolism (PE).

### Device Description:

The D-Dimer HS Latex Reagent is a suspension of polystyrene latex particles of uniform size coated with the F(ab)2 fragment of a monoclonal antibody highly specific for the D-Dimer domain included in fibrin soluble derivatives. The use of the F(ab)2 fragment allows a more specific D-Dimer detection avoiding the interference of some endogenous factors like the Rheumatoid Factor. When a plasma containing D-Dimer is mixed with the Latex Reagent and the Reaction Buffer included in the D-Dimer HS kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of D-Dimer in the sample and is determined by measuring the decrease of the transmitted light caused by the aggregates (turbidimetric immunoassay).

## Technological Characteristic Summary:

The HemosIL D-Dimer HS assay is equivalent to the currently marketed HemosIL D-Dimer HS assay, except for the Intended Use. For purposes of the Intended Use expansion, we also claim equivalence to the Biomerieux Vidas® D-Dimer Exclusion Assay, cleared under K040882.

Attachment B

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| Characteristic | Modified Device:<br>HemosIL D-Dimer HS | Predicate Device:<br>HemosIL D-Dimer HS<br>(K050544) | Predicate Device: Biomerieux<br>Vidas® D-Dimer Exclusion Assay<br>(K040882) |
|-----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| cions for use | HemosIL D-Dimer HS is an<br>automated latex enhanced<br>immunoassay for the<br>quantitative determination of<br>D-Dimer in human citrated<br>plasma on the ACL TOP for<br>use in conjunction with a<br>clinical pretest probability<br>(PTP) assessment model to<br>exclude venous<br>thromboembolism (VTE) [deep<br>venous thrombosis (DVT) and<br>pulmonary embolism (PE)]. | HemosIL D-Dimer HS is an<br>automated latex enhanced<br>immunoassay for the quantitative<br>determination of D-Dimer in<br>human citrated plasma on the ACL<br>TOP as an aid in the diagnosis of<br>venous thromboembolism (VTE)<br>[deep venous thrombosis (DVT)<br>and pulmonary embolism (PE)]. | For use in conjunction with a clinical<br>Pre-test Probability (PTP)<br>assessment model to exclude deep<br>venous thrombosis (DVT) and<br>pulmonary embolism (PE) in<br>outpatients suspected of DVT and<br>PE. |
| principle | Same as K050544 | Latex-enhanced<br>immunoturbidmetric assay | Two-step enzyme immunoassay<br>sandwich method with a final<br>fluorescent detection. |
| nent | Same as K050544 | ACL TOP instruments | VIDAS instruments |
| type | Same as K050544 | Citrated plasma | Citrated plasma |
| ator | Same as K050544 | D-Dimer Calibrator | DD2 Calibrators |
| Characteristic | Modified Device:<br>HemosIL D-Dimer HS | Predicate Device:<br>HemosIL D-Dimer HS<br>(K050544) | Predicate Device: Biomerieux<br>Vidas® D-Dimer Exclusion Assay<br>(K040882) |
| Measuring Range | Same as K050544 | 150 - 69000 ng/mL<br>with automatic rerun | 45 - 10000 ng/mL (FEU) |
| Detection Limit | Same as K050544 | 21 ng/mL | 45 ng/mL (FEU) |
| Within-run Precision (% CV) | Same as K050544 | • 8.3% at 180 ng/mL<br>• 3.7% at 314 ng/mL<br>• 2.0% at 677 ng/mL | • 5.0% at 264 ng/mL (FEU)<br>• 3.9% at 549 ng/mL (FEU)<br>• 5.3% at 7283 ng/mL (FEU) |
| Total Precision (% CV) | Same as K050544 | • 11.0% at 180 ng/mL<br>• 7.0% at 314 ng/mL<br>• 7.0% at 677 ng/mL | • 5.7% at 264 ng/mL (FEU)<br>• 5.8% at 549 ng/mL (FEU)<br>• 7.1% at 7283 ng/mL (FEU) |
| Interferences | Same as K050544 | • Hemoglobin up to 500 mg/dL<br>• Bilirubin up to 18 mg/dL<br>• Triglycerides up to 1327 mg/dL<br>• FDP up to 10 µg/mL<br>• Rheumatoid Factor up to 1400 UI/mL | None of the following factors have<br>been found to significantly influence<br>this assay: hemolysis, lipemia,<br>bilirubinemia, rheumatoid factor.<br><br>It is recommended not to use<br>samples that appear to be clearly<br>hemolyzed, lipemic, or icteric. |
| Clinical Cut-off | Same as K050544 | 230 ng/mL | 500 ng/mL (FEU) |

Substantial Equivalence Comparison Table

Attachment B

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emosIL D-Dimer HS 510(k)

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Substantial Equivalence Comparison Table (Cont.)

IemosIL D-Dimer HS 510(k)

Page 3 of 4

Attachment B

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#### Performance Data:

A multi-center management study was performed at four hospitals on 668 samples from patients admitted consecutively to the emergency unit with suspected DVT or PE. 307 patients were suspected of DVT and 361 patients were suspected of PE. As part of the study, patients underwent a PTP (pretest probability) assessment using the Wells model and were classified as having a high, moderate, or low probability of DVT or PE. Patients with a negative D-Dimer test result and a low PTP score underwent no further diagnostic testing and were followed-up after 3 months for development of DVT or PE. For patients with a negative D-Dimer test result and a moderate PTP, it was the physician's decision whether to follow-up after 3 months or to undergo imaging techniques. Patients with a positive D-Dimer test result or a high PTP score underwent imaging techniques.

The overall prevalence of DVT in the total population of samples was 20.2% (62/307). The overall prevalence of PE in the total population of samples was 16.1% (58/361). As of the 3 month followup, none of the patients that were negative through D-Dimer testing had developed DVT or PE.

The sensitivity, specificity and negative predictive value (NPV) of HemosIL D-Dimer HS for DVT and PE using the previously established clinical cut-off of 230 ng/mL is summarized below with the corresponding 95% confidence intervals (CI):

| DVT Performance | All samples | High PTP | Low + Moderate<br>PTP |
|------------------------------|----------------------------------|----------------------------------|----------------------------------|
| n | 307 | 54 | 253 |
| Sensitivity | 100.0% (62/62)<br>(94.2%-100.0%) | 100.0% (28/28)<br>(87.7%-100.0%) | 100.0% (34/34)<br>(89.7%-100.0%) |
| Specificity | 38.4% (94/245)<br>(32.2%-44.8%) | 34.6% (9/26)<br>(17.2%-55.7%) | 38.8% (85/219)<br>(32.3%-45.6%) |
| Negative<br>Predictive value | 100.0% (94/94)<br>(96.2%-100.0%) | 100.0% (9/9)<br>(66.4%-100.0%) | 100.0% (85/85)<br>(95.8%-100.0) |
| Positive<br>Predictive value | 29.1% (62/213)<br>(23.1%-35.7%) | 62.2% (28/45)<br>(46.5%-76.2%) | 20.2% (34/168)<br>(14.4%-27.1%) |
| Prevalence | 20.2% (62/307)<br>(15.8%-25.1%) | 51.9% (28/54)<br>(37.8%-65.7%) | 13.4% (34/253)<br>(9.5%-18.3%) |

| PE Performance | All samples | High PTP | Low + Moderate<br>PTP |
|------------------------------|------------------|----------------|-----------------------|
| n | 361 | 28 | 333 |
| Sensitivity | 100.0% (58/58) | 100.0% (10/10) | 100.0% (48/48) |
| | (93.8%-100.0%) | (69.2%-100.0%) | (92.6%-100.0%) |
| Specificity | 35.6% (108/303) | 16.7% (3/18) | 36.8% (105/285) |
| | (30.2%-41.3%) | (3.6%-41.4%) | (31.2%-42.7%) |
| Negative<br>Predictive value | 100.0% (108/108) | 100.0% (3/3) | 100.0% (105/105) |
| | (96.6%-100.0%) | (29.2%-100.0%) | (96.5%-100.0%) |
| Positive<br>Predictive value | 22.9% (58/253) | 40.0% (10/25) | 21.1% (48/228) |
| | (17.9%-28.6%) | (21.1%-61.3%) | (15.9%-26.9%) |
| Prevalence | 16.1% (58/361) | 35.7% (10/28) | 14.4% (48/333) |
| | (12.4%-20.3%) | (18.6%-55.9%) | (10.8%-18.7%) |

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Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo features a stylized caduceus, a symbol often associated with medicine and healthcare, with three swooping lines representing the wings of the staff. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the caduceus.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

SEP 17 2007

Carol Marble Regulatory Affairs Director Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, Massachusetts 02421

Re: k070927

Trade/Device Name: HemosIL D-Dimer HS Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/Fibrin Degradation Product Assay Regulatory Class: Class II Product Code: DAP Dated: March 30, 2007 Received: April 3, 2007

Dear Ms. Marble:

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 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 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); 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

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Page 2 – Carol Marble

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 Part 801), 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" (21CFR 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 [phone]. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at [phone]. 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 vours.

Robert J. Boctor

Robert L. Becker, M.D., Ph.D. Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Page 3 -- Carol Marble

cc: HFZ-401 DMC HFZ-404 510(k) Staff HFZ- Division D.O.

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# Indications for Use Statement

510(k) Number (if known): K070921

Device Name: HemosIL D-Dimer HS

# Indications for Use:

HemosIL D-Dimer HS is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude venous thromboembolism (VTE) in outpatients suspected of deep venous thrombosis (DVT) and pulmonary embolism (PE).

For in vitro diagnostic use.

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

Over-The-Counter Use (21 CFR 801 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 Sig

> Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K070927

HemosIL D-Dimer HS 510(k)