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

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.

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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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
K070927

B. Purpose for Submission:
To seek clearance for modification to HemosIL D-Dimer HS

C. Measurand:
D-Dimer

D. Type of Test:
Latex-enhanced immunoturbidimetric assay

E. Applicant:
Instrumentation Laboratory Co.

F. Proprietary and Established Names:
HemosIL D-Dimer HS

G. Regulatory Information:
1. Regulation section:
864.7320
2. Classification:
II
3. Product code:
DAP
4. Panel:
Hematology

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H. Intended Use:

1. Intended use(s):
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).

2. Indication(s) 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).

3. Special conditions for use statement(s): N/A

4. Special instrument requirements:
ACL TOP

I. Device Description:

The HemosIL D-Dimer HS test kit consists of latex reagent, reaction buffer, D-Dimer calibrator, and low and high D-Dimer controls. The assay is intended for use on the ACL TOP instrument.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Biomerieux Vidas D-Dimer Exclusion Assay
HemosIL D-Dimer HS

2. Predicate 510(k) number(s):
K040882
K050544

3. Comparison with predicate:

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| Similarities | | | |
| --- | --- | --- | --- |
| Item | Modified Device: HemosIL D-Dimer HS | Predicate Device: HemosIL D-Dimer HS (K050544) | Predicate Device: Biomerieux Vidas® D-Dimer Exclusion Assay (K040882) |
| Indications for use | For use in conjunction with a clinical pretest probability (PTP) assessment model to exclude venous thromboembolism (VTE) [deep venous thrombosis (DVT) and pulmonary embolism (PE)]. | | For use in conjunction with a clinical Pre-test Probability (PTP) assessment model to exclude deep venous thrombosis (DVT) and pulmonary embolism (PE) in outpatients suspected of DVT and PE. |
| Differences | | | |
| Item | Modified Device: HemosIL D-Dimer HS | Predicate Device: HemosIL D-Dimer HS (K050544) | Predicate Device: Biomerieux Vidas® D-Dimer Exclusion Assay (K040882) |
| Assay principle | Same as K050544 | Latex-enhanced immunoturbidimetric assay | Two-step enzyme immunoassay sandwich method with a final fluorescent detection |
| Measuring Range | Same as K050544 | 150 - 69000 ng/mL with automatic rerun | 45 - 10000 ng/mL (FEU) |
| Detection Limit | Same as K050544 | 21 ng/mL | 45 ng/mL (FEU) |
| Interferences | Same as K050544 | Hemoglobin up to 500 mg/dL Bilirubin up to 18 mg/dL Triglycerides up to 1327 mg/dL FDP up to 10 μg/mL Rheumatoid Factor up to 1400 UI/mL | None of the following factors have been found to significantly influence this assay: hemolysis, lipemia, bilirubinemia, rheumatoid factor. It is recommended not to use samples that appear to be clearly hemolyzed, lipemic, or icteric. |
| Clinical Cut-off | Same as K050544 | 230 ng/mL | 500 ng/mL (FEU) |

# K. Standard/Guidance Document Referenced (if applicable): N/A

# L. Test Principle:

The assay is based on the decrease of the transmitted light caused by the aggregates which form when a patient plasma containing D-Dimer is mixed with latex particles coated with monoclonal antibody. The degree of agglutination is directly

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proportional to the concentration of D-Dimer in the sample.

## M. Performance Characteristics (if/when applicable):

1. **Analytical performance**: extended claim, see original submission (K050544) for analytical studies.

a. Precision/Reproducibility:
b. Linearity/assay reportable range:
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
d. Detection limit:
e. Analytical specificity:
f. Assay cut-off:

2. **Comparison studies**:

a. **Method comparison with predicate device**:

HemosIL D-Dimer HS was used in a multi-center management study involving 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.

The Wells model was used to assess PTP (pre-test probability) score. The patients 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. Data indicated that all patients with a negative D-Dimer test and a moderate PTP received either 3 months of follow-up, or imaging with 3 months of follow-up if the imaging result was negative.
- Patients with a positive D-Dimer test result or a high PTP score were imaged.
- As of the 3 month follow-up, none of the patients that were negative through D-Dimer testing had developed DVT or PE.

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Previously established clinical cutoff of $230\mathrm{ng / mL}$ for HemosIL D-Dimer HS (K050544) was used for calculation. Statistical evaluation of the respective data sets from the four sites was performed using analysis of variance (ANOVA) to verify whether the three PE sites could be pooled and the three DVT sites could be pooled. The result was within acceptable limit $(p > 0.05)$ .

- DVT samples: Of the 307 total DVT suspected patients (179 females, 128 males). The overall prevalence of DVT in the total population of samples was $20.2\%$ (62/307).
- PE samples: Of 361 total PE suspected patients (204 females, 157 males). The overall prevalence of PE in the total population of samples was $16.1\%$ (58/361).

The sensitivity, specificity and negative predictive value (NPV) of HemosIL D-Dimer HS for DVT and PE is summarized below with the corresponding $95\%$ confidence intervals (CI):

Combined DVT Performance

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

Combined PE Performance

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

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b. Matrix comparison:

3. Clinical studies: N/A

a. Clinical Sensitivity:
b. Clinical specificity:
c. Other clinical supportive data (when a. and b. are not applicable):

4. Clinical cut-off: 230 ng/mL, same as K050544
5. Expected values/Reference range: N/A

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

1. The submitted information in this premarket notification is complete and supports a substantial equivalence decision.