HEMOSIL D-DIMER HS

K050544 · Instrumentation Laboratory CO · DAP · Apr 26, 2005 · Hematology

Device Facts

• Record ID: K050544
• Device Name: HEMOSIL D-DIMER HS
• Applicant: Instrumentation Laboratory CO
• Product Code: DAP · Hematology
• Decision Date: Apr 26, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7320
• Device Class: Class 2

Intended Use

The HemosIL D-Dimer HS is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on ACL TOP Coagulation Instrument as an aid in the diagnosis of venous thromboembolism (VTE), [deep venous thrombosis (DVT), and pulmonary embolism (PE)]

Device Story

HemosIL D-Dimer HS is an automated, quantitative latex immunoassay for D-Dimer detection in human citrated plasma. The device utilizes polystyrene latex particles coated with F(ab')2 fragments of a monoclonal antibody specific to the D-Dimer domain of fibrin derivatives. When mixed with patient plasma, the particles agglutinate; the degree of agglutination is directly proportional to D-Dimer concentration and is measured via decreased transmitted light on the ACL TOP Coagulation Instrument. The use of F(ab')2 fragments reduces interference from Rheumatoid Factor. The device is intended for use in clinical laboratory settings to aid in the diagnosis of VTE, DVT, and PE. Results are provided to clinicians to assist in diagnostic decision-making for patients presenting with symptoms of thromboembolic disease.

Clinical Evidence

Clinical performance was evaluated using 300 frozen samples from emergency unit patients with suspected PE or DVT. Using a 230 ng/mL cut-off, the device demonstrated 100% sensitivity (95% CI: 95.4-100%), 47% specificity (95% CI: 40.1-53.6%), and 100% NPV (95% CI: 96.5-100%). A secondary study of 100 outpatient samples confirmed 100% sensitivity and 100% NPV at the same cut-off. ROC analysis yielded an AUC of 0.902 (p<0.001). Analytical precision was established with total %CV ranging from 4.9% to 11%.

Technological Characteristics

Quantitative latex immunoassay; polystyrene latex particles coated with F(ab')2 monoclonal antibody fragments. Energy source: optical (transmitted light measurement). Dimensions/form factor: kit includes calibrator, latex reagent, and reaction buffer for use on ACL TOP Coagulation Instrument. Connectivity: automated instrument-based. Sterilization: not applicable (reagent kit).

Indications for Use

Indicated for patients with suspected venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), to aid in diagnosis via quantitative D-Dimer measurement in citrated plasma.

Predicate Devices

• HemosIL D-Dimer (K972696)

Submission Summary (Full Text)

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K050544

# APR 2 6 2005 Section 3 HemosIL D-Dimer HS 510(k) Summary (Summary of Safety and Effectiveness)

## Applicant Contact Information:

| Applicant: | Instrumentation Laboratory Co. |
|-------------------|--------------------------------------------|
| Address: | 113 Hartwell Avenue<br>Lexington, MA 02421 |
| Contact Person: | Carol Marble, Regulatory Affairs Director |
| Phone Number: | 781-861-4467 |
| Fax Number: | 781-861-4207 |
| Preparation Date: | February 28, 2005 |

### Device Trade Name:

HemosIL D-Dimer HS

### Regulatory Information:

Classification Name: Fibrinogen and Fibrin Split Products, Antigen, Antiserum, Control Device Class: Class II 864.7320 Regulation No .: DAP

Product Code: Hematology Panel:

#### Predicate Device:

HemosIL D-Dimer K972696

## Device Intended Use / Description:

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 as an aid in the diagnosis of venous thromboembolism (VTE) [deep venous thrombosis (DVT) and pulmonary embolism (PE)].

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 Latcx 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).

# Statement of Technological Characteristics of the Device Compared to Predicate Device:

HemosIL D-Dimer HS is substantially equivalent to the commercially available predicate device (HemosIL D-Dimer) in performance and intended use.

| Section 3 | HemosIL D-Dimer HS 510(k) | Page 1 of |
|-----------|---------------------------|-----------|
|-----------|---------------------------|-----------|

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# Section 3 (Cont.) HemosIL D-Dimer HS 510(k) Summary (Summary of Safety and Effectiveness)

# Summary of Performance Data:

### Precision

Within run and total precision assessed over multiple runs using three levels of control plasma gave the following results:

| ACL TOP: | Mean (ng/mL) | CV% (Within run) | CV% (Total) |
|------------------------------|--------------|------------------|-------------|
| D-Dimer Plasma Pool | 179.6 | 8.3 | 11.0 |
| HemosIL D-Dimer Low Control | 313.8 | 3.7 | 7.0 |
| HemosIL D-Dimer High Control | 677.2 | 2.0 | 7.0 |

## Method Comparison

In a method comparison study on an ACL TOP using citrated plasma samples (n=229) ranging in D-Dimer concentration from 87 to 20869 ng/mL, the correlation statistics for HemosIL D-Dimer HS versus the predicate device are shown below:

| IL System<br>.<br>****************************************************************************************************************************************************************************** | Slope | Intercept | and and a concession to manufacturer programment |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------|-----------|--------------------------------------------------|
| TOP<br>ACL | 0 0407 | -50.298 | 0.973 |

## Management Study

An outcome study was performed on 300 frozen samples from patients admitted consecutively to an emergency unit with suspected PE or DVT (frequency of venous thromboembolic disease: 26%). Of the 300 samples, 78 were confirmed as VTE positive (47 PE and 31 DVT) by standard objective tests and the remaining 222 were confirmed as negative.

| Instrument | N | Cut-off | % Sensitivity<br>(95% CI) | % Specificity<br>(95% CI) | % NPV<br>(95% CI) |
|------------|-----|-----------|---------------------------|---------------------------|-------------------------|
| ACL TOP | 300 | 230 ng/mL | 100%<br>(95.4% to 100%) | 47%<br>(40.1% to 53.6%) | 100%<br>(96.5% to 100%) |

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APR 2 6 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Carol Marble Regulatory Affairs Director Instrumentation Laboratory Co. 113 Hartwell Avenue Lexington, MA 02421

Re: k050544

> Trade/Device Name: HemosIL D-Dimer HS Regulation Number: 21 CFR § 864.7320 Regulation Name: Fibrinogen and Fibrin Split Products, Antigen, Antiserum, Control Regulatory Class: II Product Code: DAP Dated: February 28, 2005 Received: March 2, 2005

Dear Mr. 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 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.

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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" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Robert Beckerf

Robert L. Becker, Jr., MD, PHD 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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Indications for Use

510(k) Number (if known): K050544

Device Name: HemosL 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 as an aid in the diagnosis of venous thromboembolism (VTE) [deep venous thrombosis (DVT) and pulmonary embolism (PE)].

For in vitro diagnostic use.

Prescription Use ﺮ (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) K050544

HemosIL D-Dimer HS 510(k)