HEMOSIL D-DIMER

K073042 · Instrumentation Laboratory · DAP · Jul 31, 2008 · Hematology

Device Facts

• Record ID: K073042
• Device Name: HEMOSIL D-DIMER
• Applicant: Instrumentation Laboratory
• Product Code: DAP · Hematology
• Decision Date: Jul 31, 2008
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7320
• Device Class: Class 2

Intended Use

HemosIL D-Dimer is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on IL Coagulation Systems. HemosIL D-Dimer is used 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 Story

HemosIL D-Dimer is an automated latex-enhanced immunoturbidimetric assay for quantitative measurement of fibrin degradation products in citrated plasma. Device utilizes latex particles coated with monoclonal antibodies specific to D-Dimer domain. Input is patient citrated plasma; output is D-Dimer concentration (ng/mL) measured via light transmission decrease during agglutination. Used in clinical laboratory settings on IL Coagulation Systems (e.g., ACL TOP, ACL ELITE). Healthcare providers use results alongside clinical pretest probability (PTP) scores to rule out DVT/PE. Negative results in low/moderate PTP patients allow exclusion of VTE, potentially reducing need for diagnostic imaging. Assay performance validated across multi-center management studies.

Clinical Evidence

Multi-center management study evaluated 1,229 patients suspected of DVT or PE using ACL TOP and ACL ELITE instruments. Patients classified by Wells PTP model. Primary endpoint: exclusion of VTE in negative D-Dimer/low-moderate PTP patients. Results: Sensitivity for DVT/PE ranged 97.6%–100.0%; NPV ranged 99.1%–100.0%. One false negative occurred on ACL ELITE. Statistical evaluation (ANOVA) confirmed site pooling validity (p>0.05).

Technological Characteristics

Latex-enhanced immunoturbidimetric assay. Reagents: latex particles coated with monoclonal antibody. Energy source: optical (light transmission). Form factor: liquid reagent kit for automated IL Coagulation Systems. Connectivity: integrated with IL Coagulation System platforms. Sterilization: N/A.

Indications for Use

Indicated for quantitative D-Dimer determination in human citrated plasma to exclude venous thromboembolism (VTE) in outpatients suspected of deep venous thrombosis (DVT) or pulmonary embolism (PE), used in conjunction with clinical pretest probability (PTP) assessment.

Predicate Devices

• HemosIL D-Dimer HS (K070927)

Submission Summary (Full Text)

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X073042

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

### Applicant Contact Information:

| Applicant: | Instrumentation Laboratory Co. | |
|-------------------|--------------------------------------------|-------------|
| Address: | 113 Hartwell Avenue<br>Lexington, MA 02421 | JUL 31 2008 |
| Contact Person: | Carol Marble, Regulatory Affairs Director | |
| Phone Number: | 781-861-4467 | |
| Fax Number: | 781-861-4207 | |
| Preparation Date: | June 27, 2008 | |

#### Device Trade Name:

HemosIL D-Dimer

## 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:

K070927 HemosIL D-Dimer HS

## Device Intended Use:

HemosIL D-Dimer is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on IL Coagulation Systems 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 cmbolism (PE).

## Device Description:

The D-Dimer Latex Reagent is a suspension of polystyrenc latex particles of uniform size coated with a monoclonal antibody highly specific for the D-Dimer domain included in fibrin soluble derivatives. When a plasma containing D-Dimer is mixed with the Latex Reagent and the Reaction Buffer included in the D-Dimer 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 at 405 nm caused by the aggregates (turbidimetric immunoassay).

## Technological Characteristic Summary:

The HemosIL D-Dimer assay is equivalent to the currently marketed HemosIL D-Dimer assay (K050278), except for the Intended Use. For purposes of the Intended Use expansion, we also claim equivalence to the HemosIL D-Dimer HS assay (K070927).

#### Attachment B

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| Characteristic | Modified Device:<br>HemosIL D-Dimer | Predicate Device:<br>Current HemosIL D-Dimer<br>(K050278) | Predicate Device:<br>HemosIL D-Dimer HS<br>(K070927) |
|--------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for use | HemosIL D-Dimer is an automated latex<br>enhanced immunoassay for the<br>quantitative determination of D-Dimer in<br>human citrated plasma on IL Coagulation<br>Systems for use in conjunction with a<br>clinical pretest probability (PTP)<br>assessment model to exclude venous<br>thromboembolism (VTE) in outpatients<br>suspected of deep venous thrombosis<br>(DVT) and pulmonary embolism (PE). | HemosIL D-Dimer is an automated<br>latex enhanced immunoassay for the<br>quantitative determination of<br>D-Dimer in human citrated plasma<br>on IL Coagulation Systems as an aid<br>in the diagnosis of 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 human<br>citrated plasma on the ACL TOP for<br>use in conjunction with a clinical<br>pretest probability (PTP) assessment<br>model to exclude venous<br>thromboembolism (VTE) [deep<br>venous thrombosis (DVT) and<br>pulmonary embolism (PE)]. |
| Assay principle | Latex-enhanced<br>immunoturbidmetric assay | Same | Same |
| Instruments | IL Coagulation Systems | Same | ACL TOP instruments only |
| Sample type | Citrated plasma | Same | Same |
| Calibrator | Kit Calibrator | Same | Same |
| Quality Control | HemosIL D-Dimer Controls | Same | Same |
| Measuring Range | 200 - 5250 ng/mL<br>with automatic rerun | Same | 150 - 69000 ng/mL<br>with automatic rerun |
| Detection Limit | ACL Family<br>ACL Futura/ACL Advance<br>ACL TOP | Same | 21 ng/mL<br>ACL TOP |
| | 140 ng/mL<br>156 ng/mL<br>69 ng/mL | | |
| Characteristic | Modified Device:<br>HemosIL D-Dimer | Predicate Device:<br>HemosIL D-Dimer<br>(K050278) | Predicate Device:<br>HemosIL D-Dimer HS<br>(K070927) |
| Within-run<br>Precision (% CV) | ACL Family:<br>4.5% at 246 ng/mL 6.01% at 310 ng/mL 2.42% at 732 ng/mL ACL Futura/ACL Advance: 11.82% at 304 ng/mL 3.59% at 813 ng/mL ACL TOP: 6.8% at 282 ng/mL 4.6% at 340 ng/mL 2.5% at 729 ng/mL | Same | ACL TOP: 8.3% at 180 ng/mL 3.7% at 314 ng/mL 2.0% at 677 ng/mL |
| Interferences | ACL Family and<br>ACL Futura/ACL Advance Systems: Hemoglobin up to 50 mg/dL Bilirubin up to 5 mg/dL Lipids up to 1000 mg/dL Rheumatoid Factor up to 60 IU/mL ACL TOP Hemoglobin up to 100 mg/dL Bilirubin up to 10 mg/dL Triglycerides up to 1500 mg/dL The presence of Rheumatoid Factor may produce an overestimation of the test result | Same | ACL TOP: Hemoglobin up to 500 mg/dL Bilirubin up to 18 mg/dL Triglycerides up to 1327 mg/dL Rheumatoid Factor up to 1400 UI/mL |
| Clinical Cut-off | 230 ng/mL | Same | Same |

Substantial Equivalence Comparison Table

Attachment B

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Substantial Equivalence Comparison Table (Cont.)

Attachment B

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## Performance Data:

A multi-center management study was performed at four hospitals on patients admitted consecutively to the emergency unit with suspected DVT or PE using representative IL Coagulation Systems: an ACL TOP (632 samples) and an ACL ELITE (629 samples). 302 patients on the ACL TOP and 298 patients on an ACL ELITE were suspected of DVT; 330 patients on the ACL TOP and 331 patients on the ACL ELITE 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.

There was one case during the study where a patient with a moderate PTP score and a negative D-Dimer test result on the ACL ELITE was confirmed for PE through imaging techniques. This same sample gave a positive D-Dimer test result on the ACL TOP.

The overall prevalence of DVT in the total population of samples was 19.5% (59/302) on the ACL TOP and 20.5% (61/298) on the ACL ELITE. The overall prevalence of PE in the total population of samples was 15.2% (50/330) on the ACL. TOP and 15.1% (50/331) on the ACL ELITE.

The sensitivity, specificity and negative predictive value (NPV) of HemosIL D-Dimer on the ACL. TOP and ACL ELITE 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):

| ACL TOP | | | |
|------------------------------|------------------------------------|----------------------------------|----------------------------------|
| DVT Performance | All samples | High PTP | Low + Moderate<br>PTP |
| n | 302 | 53 | 249 |
| Sensitivity | 100.0% (59/59)<br>(93.9%-100.0%) | 100.0% (27/27)<br>(87.2%-100.0%) | 100.0% (32/32)<br>(89.1%-100.0%) |
| Specificity | 41.6% (101/243)<br>(35.3%-48.0%) | 34.6% (9/26)<br>(17.2%-55.7%) | 42.4% (92/217)<br>(35.7%-49.3%) |
| Negative<br>Predictive value | 100.0% (101/101)<br>(96.4%-100.0%) | 100.0% (9/9)<br>(66.4%-100.0%) | 100.0% (92/92)<br>(96.1%-100.0%) |
| Positive<br>Predictive value | 29.4% (59/201)<br>(23.2%-36.2%) | 61.4% (27/44)<br>(45.5%-75.6%) | 20.4% (32/157)<br>(14.4%-27.5%) |
| Prevalence | 19.5% (59/302)<br>(15.2%-24.5%) | 50.9% (27/53)<br>(36.8%-64.9%) | 12.9% (32/249)<br>(9.0%-17.7%) |
| PE Performance | All samples | High PTP | Low + Moderate<br>PTP |
| n | 330 | 24 | 306 |
| Sensitivity | 100.0% (50/50)<br>(92.9%-100.0%) | 100.0% (7/7)<br>(59.0%-100.0%) | 100.0% (43/43)<br>(91.8%-100.0%) |
| Specificity | 29.3% (82/280)<br>(24.0%-35.0%) | 17.6% (3/17)<br>(3.8%-43.4%) | 30.0% (79/263)<br>(24.6%-36.0%) |
| Negative<br>Predictive value | 100.0% (82/82)<br>(95.6%-100.0%) | 100.0% (3/3)<br>(29.2%-100.0%) | 100.0% (79/79)<br>(95.4%-100.0%) |
| Positive<br>Predictive value | 20.2% (50/248)<br>(15.4%-25.7%) | 33.3% (7/21)<br>(14.6%-57.0%) | 18.9% (43/227)<br>(14.1%-24.7%) |
| | 15.2% (50/330) | 29.2% (7/24) | 14.1% (43/306) |

HemosIL D-Dimer 510(k) Response (06/27/08)

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## Performance Data (Cont.):

| ACL ELITE | | | |
|---------------------------|-----------------------------------|----------------------------------|-----------------------------------|
| DVT Performance | All samples | High PTP | Low + Moderate<br>PTP |
| n | 298 | 54 | 244 |
| Sensitivity | 100.0% (61/61)<br>(94.1%-100.0%) | 100.0% (29/29)<br>(88.1%-100.0%) | 100.0% (32/32)<br>(89.1%-100.0%) |
| Specificity | 33.8% (80/237)<br>(27.8%-40.2%) | 24.0% (6/25)<br>(9.4%-45.1%) | 34.9% (74/212)<br>(28.5%-41.7%) |
| Negative Predictive Value | 100.0% (80/80)<br>(95.5%-100.0%) | 100.0% (6/6)<br>(54.1%-100.0%) | 100.0% (74/74)<br>(95.1%-100.0%) |
| Positive Predictive Value | 28.0% (61/218)<br>(22.1%-34.4%) | 60.4% (29/48)<br>(45.3%-74.2%) | 18.8% (32/170)<br>(13.2%-25.5%) |
| Prevalence | 20.5% (61/298)<br>(16.0%-25.5%) | 53.7% (29/54)<br>(39.6%-67.4%) | 13.1% (32/244)<br>(9.1%-18.0%) |
| PE Performance | All samples | High PTP | Low + Moderate<br>PTP |
| n | 331 | 25 | 306 |
| Sensitivity | 98.0% (49/50)<br>(89.4%-99.9%) | 100.0% (8/8)<br>(63.1%-100.0%) | 97.6% (41/42)<br>(87.4%-99.9%) |
| Specificity | 41.3% (116/281)<br>(35.5%-47.3%) | 41.2% (7/17)<br>(18.4%-67.1%) | 41.3% (109/264)<br>(35.3%-47.5%) |
| Negative Predictive Value | 99.1% (116/117)<br>(95.3%-100.0%) | 100.0% (7/7)<br>(59.0%-100.0%) | 99.1% (109/110)<br>(95.0%-100.0%) |
| Positive Predictive Value | 22.9% (49/214)<br>(17.4%-29.1%) | 44.4% (8/18)<br>(21.5%-69.2%) | 20.9% (41/196)<br>(15.4%-27.3%) |
| Prevalence | 15.1% (50/331) | 32.0% (8/25) | 13.7% (42/306) |

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the bird-like figure.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

## JUL 31 2008

Instrumentation Laboratory c/o Carol Marble Regulatory Affairs Director 113 Hartwell Avenue Lexington, Massachusetts 02421

Re: k073042

Trade/Device Name: Hemosil D-Dimer Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/Fibrin Degradation Product Assay Regulatory Class: Class II Product Code: DAP Dated: June 27, 2008 Received: June 30, 2008

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 notification. The FDA finding of substantial equivalence of your device to a legally marketed

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Page 2 - Instrumentation Laboratory

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 yours.

Mana In Chan

Maria M. Chan, Ph.D. Acting 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 Statement

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: HemosIL D-Dimer

## Indications for Use:

HemosIL D-Dimer is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on II. Coagulation Systems 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)

Josephine Bautista
Division Sign Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K073042

HemosIL D-Dimer 510(k)

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