DIAZYME D-DIMER ASSAY KIT,CALIBRATOR SETAND CONTROL SET

K112120 · Diazyme Laboratories · GHH · Jan 24, 2013 · Hematology

Device Facts

• Record ID: K112120
• Device Name: DIAZYME D-DIMER ASSAY KIT,CALIBRATOR SETAND CONTROL SET
• Applicant: Diazyme Laboratories
• Product Code: GHH · Hematology
• Decision Date: Jan 24, 2013
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7320
• Device Class: Class 2

Intended Use

The D-Dimer Assay is for the quantitative determination of fibrinogen/fibrin degradation products (D-Dimer) in human plasma. Measurement of D-Dimer is used as an aid in detecting the presence of intravascular coagulation and fibrinolysis. For in vitro diagnostic use only. The D-Dimer assay calibrator set is intended for use in the calibration of the D-Dimer assay only. For in vitro diagnostic use only. The D-Dimer Assay Control Set is intended for use as quality controls for the Diazyme D-Dimer assay only. For in vitro diagnostic use only.

Device Story

Diazyme D-Dimer Assay is a latex-enhanced immunoturbidimetric in vitro diagnostic test. It uses human citrated plasma samples. Mouse monoclonal anti-human D-Dimer antibodies coated on latex particles bind to D-Dimer proteins in the sample, causing agglutination. This agglutination increases turbidity, which is measured optically. The instrument calculates D-Dimer concentration by interpolating the signal against a 6-point calibration curve. Used in clinical laboratories to assist physicians in detecting intravascular coagulation and fibrinolysis. Results provide quantitative data to support clinical decision-making regarding coagulation status.

Clinical Evidence

No clinical diagnostic studies performed. Analytical performance established via bench testing on Roche Modular P instrument. Precision evaluated per CLSI EP5-A2 (CV ≤ 8% for analyte > 0.05 µg/mL FEU). Linearity demonstrated from 0.003 to 8.6 µg/mL FEU. Method comparison against predicate (k062203) using 88 unique patient samples (intensive care, trauma, post-operative) showed slope 1.0 ± 0.1, r²≥0.90, intercept ± 0.15. Interference testing showed no significant interference for common substances.

Technological Characteristics

Latex-enhanced immunoturbidimetric assay. Reagents: Tris-buffer, mouse monoclonal anti-human D-Dimer coated latex particles (<0.2%), sodium azide (0.09%). Form factor: Liquid reagent kit with lyophilized calibrators and controls. Connectivity: Designed for use on clinical chemistry analyzers (e.g., Roche Modular P).

Indications for Use

Indicated for quantitative determination of D-Dimer in human citrated plasma to aid in detecting intravascular coagulation and fibrinolysis. For use in clinical settings (ICU, trauma, post-operative, OR).

Predicate Devices

• Roche TINA-QUANT D-Dimer System (k062203)

Submission Summary (Full Text)

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## K1121205

#### 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92

#### Submitter's name:

Diazyme Laboratories

## JAN 2 4 2013

Submitter's address:

12889 Gregg Court Poway, CA 92064 USA

Name of Contact Person:

Dr. Abhijit Datta Diazyme Laboratories 12889 Gregg Court . Poway, CA 92064 Phone: [phone] Fax: [phone]

January 24, 2013

Date the Summary was Prepared:

Name of the Device

D-Dimer Assay Kit D-Dimer Assay Calibrator Set D-Dimer Assay Control Set

Diazyme D-Dimer Assay Kit

Diazyme D-Dimer Assay Calibrator Set Diazyme D-Dimer Assay Control Set

Trade Name:

Common/Usual Name

Device Classification Name

Product code:

GHH Fibrin Split Products DAP Fibrinogen and Fibrin Split Products, Antigen, Antiserum, Control JIT Calibrator, Secondary

. Panel:

Submission Type

Regulation Number

#### Hematology (81)

D-Dimer Assay

D-Dimer Test System

510k

#### 21CFR 866.7320

1

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Device Class Class II Predicate Device: Roche TINA-QUANT D-DIMER SYSTEM (k062203) Manufacturing Address Diazyme Laboratories 12889 Gregg Court Poway, CA 92064 USA

Establishment Registration 2032900

#### Description of the Device:

#### Summarv

Thrombus formation is normally followed by an immediate fibrinolytic response. The resultant generation of plasmin causes the release of fibrin degradation products (predominantly containing D-Dimer) into the circulation.

#### Assay Principle

Diazyme's D-Dimer Assay is based on a latex enhanced immunoturbidimetric assay. D-Dimer proteins in the sample bind to the specific anti-D-Dimer antibody, which is coated on latex particles, and causes agglutination. The degree of the turbidity caused by agglutination can be measured optically and is proportional to the amount of D-Dimer in the sample. The instrument calculates the D-Dimer concentration of a patient specimen by interpolation of the obtained signal of a 6-point calibration curve.

#### Indications for Use:

The D-Dimer Assay is for the quantitative determination of fibrin degradation products (D-Dimer) in human plasma. Measurement of D-Dimer is used as an aid in detecting the presence of intravascular coagulation and fibrinolysis. For in vitro diagnostic use only.

The Diazyme D-Dimer Calibrator Set is intended for use of the calibration of the Diazyme D-Dimer Assay only. For in vitro diagnostic use only.

The Diazyme D-Dimer Control Set is intended for use as quantitative quality controls for the Diazyme D-Dimer Assay only. For in vitro diagnostic use only.

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| Roche Tina-Quant D-Dimer k062203 | Diazyme D-Dimer Assay |
|-------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Reagent 1<br>buffer solution, ready to use | Reagent 1<br>100 mM Tris-buffer solution with 0.09% so-<br>dium azide, ready to use |
| Reagent 2<br>Anti-D-Dimer latex suspension (0.15%) in<br>pH 7.2 buffer matrix | Reagent 2<br>Suspension of latex particles (<0.2%) coated<br>with mouse monoclonal anti-human D-Dimer<br>with 0.09% sodium azide, ready to use.<br>Calibrators<br>Five lyophilized calibrators, one saline cali-<br>brator |
| Calibrator set | Calibrator set |
| 1 x 2.5 mL Diluent, Cal 1<br>1 x 0.5 mL Calibrator 6 | Saline (as cal 0, not provided)<br>1 x 1.0 mL Calibrator 1<br>1 x 1.0 mL Calibrator 2<br>1 x 1.0 mL Calibrator 3<br>1 x 1.0 mL Calibrator 4<br>1 x 1.0 mL Calibrator 5 |
| Control Set serum based | Control Set serum based |
| 1 x 0.5mL Control 1 | 1 x 1.0mL Control 1 |
| 1 x 0.5mL Control 2 | 1 x 1.0mL Control 2 |

## Table 1 Summary of Assay Kit Components

Comparison of new device to predicate: The charts below identify similarities and differences between the predicate device and the Diazyme D-Dimer Assay.

### Indications for Use

| Roche Tina-Quant D-Dimer k062203 | Diazyme D-Dimer Assay | Equivalency |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|
| For the in vitro quantitative determina-<br>tion of fibrin degradation products in-<br>cluding D-Dimer and X-oligomers. | The Diazyme D-Dimer Assay is for the<br>quantitative determination of fibrino-<br>gen/fibrin degradation products (D-<br>Dimer) in human plasma. Measurement<br>of D-Dimer is used as an aid in detecting<br>the presence of intravascular coagulation<br>and fibrinolysis. For in vitro diagnostic<br>use only. | Same |
| Aid in detecting the presence and degree<br>of intravascular coagulation and fibri-<br>nolysis and in monitoring therapy for<br>disseminated intra vascular coagulation. | | |
| In conjunction with a non-high clinical | | |

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| probability assessment, a normal (<0.5 µg FEU/mL) result excludes deep vein thrombosis (DVT) and pulmonary embolism (PE) with high sensitivity. | | |
|-------------------------------------------------------------------------------------------------------------------------------------------------|--|--|
|-------------------------------------------------------------------------------------------------------------------------------------------------|--|--|

## Principle

| Roche Tina-Quant D-Dimer k062203 | Diazyme D-Dimer Assay | Equivalency |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|
| Latex particles of uniform size are<br>coated with monoclonal antibodies<br>(F(ab')2 fragments) to the D-Dimer epi-<br>tope. The antigen/antibody complexes<br>produced by the addition of samples<br>containing D-Dimer lead to an increase<br>in the turbidity of the test reactants. The<br>change in absorbance with time is de-<br>pendent on the concentration of D-<br>Dimer epitopes in the sample. | Diazyme D-Dimer Assay is based on a<br>latex enhanced immunoturbidimetric<br>assay. D-Dimer proteins in the sample<br>bind to the specific anti-D-Dimer anti-<br>body, which is coated on latex particles,<br>and causes agglutination. The degree of<br>the turbidity caused by agglutination<br>can be measured optically and is pro-<br>portional to the amount of D-Dimer in<br>the sample. The instrument calculates<br>the D-Dimer concentration of a patient<br>specimen by interpolation of the ob-<br>tained signal of a 6-point calibration<br>curve. | Same |

## Test Objective

| Roche Tina-Quant D-Dimer k062203 | Diazyme D-Dimer Assay | Equivalency |
|---------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------|-------------|
| For the <i>in vitro</i> quantitative determina-<br>tion of D-Dimer in citrated or li-heparin<br>plasma. | For the <i>in vitro</i> quantitative determina-<br>tion of D-Dimer in citrated plasma. | Same |

·

## Type of Test

| Roche Tina-Quant D-Dimer k062203 | Diazyme D-Dimer Assay | Equivalency |
|----------------------------------|-----------------------|-------------|
| Quantitative | Quantitative | Same |

## Specimen Type

| Roche Tina-Quant D-Dimer k062203 | Diazyme D-Dimer Assay | Equivalency |
|----------------------------------|-----------------------|-------------|
|----------------------------------|-----------------------|-------------|

. . :

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| Human citrated or li-heparin plasma. | Human citrated plasma. | Same |
|------------------------------------------------------------|------------------------------------------------------------|-------------|
| Product Type | | |
| Roche Tina-Quant D-Dimer k062203 | Diazyme D-Dimer Assay | Equivalency |
| Assay reagent kit, calibrator kit, quality<br>control kit. | Assay reagent kit, calibrator kit, quality<br>control kit. | Same |

#### Performance

| Roche Tina-Quant D-Dimer k062203 | Diazyme D-Dimer Assay |
|-------------------------------------------------------------------|------------------------------------------------------------------------|
| Working Range: 0.15-9 µg/mL FEU D-<br>Dimer | Linear Range: 0.15-8 µg/mL FEU D-Dimer |
| Precision: CV% of 0.8 - 8.3% | Precision: CV% of 1.4% - 6.2% |
| Methods Comparion (vs Asserachrom<br>D-Dimer k862156): | Methods Comparion (vs. Roche Tina-Quant D-<br>Dimer k062203): |
| Correlation Coefficient: 0.775<br>Slope/Intercept: y = 1.03/-0.11 | Correlation Coefficient: 0.939<br>Slope/ y Intercept: y = 0.979 /-0.10 |

#### Calibrator Comparison

| Roche D-Dimer Calibrator | Diazyme D-Dimer Calibrator | Equivalency |
|------------------------------------------------------------------|------------------------------------------------------------------|-------------|
| Separately packaged lot specific<br>calibrator kit. Lyophilized. | Separately packaged lot specific<br>calibrator kit. Lyophilized. | Same |

#### Control Comparison

| Roche D-Dimer Control I/II | Diazyme D-Dimer Control | Equivalency |
|-----------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------|-------------|
| Separately packaged quality control kit<br>designed for specific assay.<br>Lyophilized. | Separately packaged quality control set<br>designed for specific assay.<br>Lyophilized. | Same |

## Performance Testing Summaries:

The data (precision, method comparison, linearity, LOB/LOD/LOQ and interference) determined using Roche Modular P is given below.

## Precision

Internal Study

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The precision of the Diazyme D-Dimer Assay was evaluated according to Clinical Laboratory Standards Institute EP5-A guideline.

In the study, three levels of pooled citrated plasma specimens containing 0.60 µg/mL, 2.41 ug/mL and 5.88 µg/mL FEU, respectively. The low plasma sample was unaltered. The other two plasma samples were spiked with D-Dimer stock solution to targeted concentrations and assayed. Three levels of D-Dimer controls containing 0.97, 2.99 and 7.47 µg/mL FEU, respectively were also tested with 2 runs per day with duplicates over 20 working days with three lops of reagent and three lots of calibrators. The combined results are shown below:

| | Level 1: 0.60 µg/mL<br>FEU | Level 2: 2.41 µg/mL<br>FEU | Level 3: 5.88 µg/mL<br>FEU |
|-----------------|----------------------------|----------------------------|----------------------------|
| Data Points N | 240 | 240 | 240 |
| Mean (g/mL FEU) | 0.60 | 2.41 | 5.88 |
| SD (g/mL FEU) | 0.03 | 0.05 | 0.08 |
| CV% | 5.0% | 2.0% | 1.4% |

Plasma Samples Within Run Precision

#### Plasma Samples Total Precision

| | Level 1: 0.60 µg/mL<br>FEU | Level 2: 2.41 µg/mL<br>FEU | Level 3: 5.88 µg/mL<br>FEU |
|-----------------|----------------------------|----------------------------|----------------------------|
| Data Points N | 240 | 240 | 80 |
| Mean (g/mL FEU) | 0.60 | 2.41 | 5.88 |
| SD (g/mL FEU) | 0.04 | 0.07 | 0.19 |
| CV% | 6.2% | 2.7% | 3.2% |

## Control Samples Within Run Precision

| | Level 1: 0.97 µg/mL | Level 2: 2.99 µg/mL | Level 2: 7.47 µg/mL |
|-----------------|---------------------|---------------------|---------------------|
| | FEU | FEU | FEU |
| Data Points N | 240 | 240 | 240 |
| Mean (g/mL FEU) | 0.97 | 2.99 | 7.47 |
| SD (g/mL FEU) | 0.03 | 0.05 | 0.11 |
| CV% | 2.9% | 1.6% | 1.4% |

#### Control Samples Total Precision

| | Level 1: 0.97 µg/mL<br>FEU | Level 2: 2.99 µg/mL<br>FEU | Level 2: 7.47 µg/mL<br>FEU |
|-----------------|----------------------------|----------------------------|----------------------------|
| Data Points N | 240 | 240 | 240 |
| Mean (g/mL FEU) | 0.97 | 2.99 | 7.47 |
| SD (g/mL FEU) | 0.04 | 0.08 | 0.27 |
| CV% | 4.4% | 2.8% | 3.6% |

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#### External Study

The precision of the Diazyme D-Dimer Assay was also evaluated at three external sites by intended users. In the study, four different patient samples of citrated plasma containing 0.36 ug/mL, 1.06 µg/mL, 3.53 µg/mL and 7.20 µg/mL FEU respectively, were tested in duplicates with 2 runs per day over 5 nonconsecutive working days using three lots of reagent, three lots of calibrators, three different clinical testing sites, three different operators and three different instruments. The results are shown below:

| Sample | within<br>run | between run | between day | between lot | total | Mean<br>µg/mL<br>FEU |
|--------|---------------|-------------|-------------|-------------|-------|----------------------|
| 1 | 8.9% | 8.3% | 7.6% | 7.1% | 11.5% | 0.36 |
| 2 | 3.8% | 3.6% | 7.4% | 8.3% | 8.3% | 1.06 |
| 3 | 2.9% | 3.9% | 3.1% | 0.7% | 4.7% | 3.53 |
| 4 | 1.6% | 3.1% | 2.4% | 1.5% | 3.5% | 7.20 |

#### LOB, LOD, and LOO

The LOB, LOD, LOQ of the Diazyme D-Dimer Assay was determined according to CLSI EP17-A. LOB was determined to be 0.06 µg/mL FEU; LOD was determined to be 0.09 µg/mL FEU. To determine LOQ, specimens with mean measured concentrations ranging from 0.02 to 0.93 were assayed. Based on the EP evaluator-8 fitted model, the LOQ (lowest concentration for which CV is less than a target of 20%) is 0.15 µg/mL FEU.

#### Linearity

Eleven levels of the D-Dimer linearity set were prepared by diluting a specimen containing 8.0 ug/mL FEU with saline according to Clinical and Laboratory Standards Institute EP6-A and tested on Modular P. Diazyme D-Dimer assay is linear from 0.15 to 8.0 µg/mL FEU.

#### Method Comparison

To demonstrate accuracy, the Diazyme D-Dimer Assay was evaluated by testing individual citrated plasma from the intended target population (Intensive Care Unit, Obstetrics, Trauma, Post-Operative and Operating Room) with comparison to a legally marketed D-Dimer revince it the manufacturer site and two external clinical laboratories. A total of 128 citrated plasma samples (88 unique samples) with D-Dimer ranging from 0.17 to 7.95 µg/mL FEU were compared. Repeat testing was addressed by bootstrapped regression analysis with stratification is shown below:

| Parameter | Total of 3 sites |
|-----------|------------------|
| Slope | 0.979 |
| 95% CI | 0.909 to 1.060 |
| Intercept | -0.106 |
| 95% CI | -0.260 to 0.026 |
| R2 | 0.939 |

The bias around the medical decision point is -0.12 µg/ml FEU

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#### Interference

The following substances do not interfere with this assay at the levels tested (less than 10% bias):

Hemoglobin: Bilirubin: Bilirubin Conjugated: Triglycerides: Ascorbic acid: Rheumatoid Factor Heparin HAMA

up to 500 mg/dL up to 40 mg/dL up to 40 mg/dL up to 1000 mg/dL up to 176 mg/dL up to 100 IU/mL up to 1.5 IU/mL up to 490 ng/mL

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#### DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features the department's name in a circular arrangement around the perimeter. In the center of the logo is a stylized graphic of an abstract symbol, consisting of three curved lines that resemble a person embracing another person.

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

Diazyme Laboratories c/o Dr. Abhijit Datta 12889 Gregg Court Poway, CA 92064

Jan 24, 2013

Re: k112120

Trade/Device Name: Diazyme D-Dimer Assay Kit, Diazyme D-Dimer Assay Control Set and Diazyme D-Dimer Assay Calibrator Set Regulation Number: 21 CFR §864.7320 Regulation Name: Fibrinogen/fibrin degradation products assay Regulatory Class: Class II Product Code: GHH, DAP, JIT Dated: January 17, 2013

Received: January 18, 2013

Dear Dr. Datta:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

{9}------------------------------------------------

Page 2 - Dr. Abhijit Datta

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH0ffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours.

# Maria M. Chan -S

Maria M. Chan, Ph.D.

Director

Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological

Health Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (If Known): K112120

Device Name: Diazyme D-Dimer Assay Kit, Diazyme D-Dimer Assay Calibrator Set, Diazyme D-Dimer Assay Control Set.

Indications for Use:

The D-Dimer Assay is for the quantitative determination of fibrin degradation products (D-Dimer) in human plasma. Measurement of D-Dimer is used as an aid in detecting the presence of intravascular coagulation and fibrinolysis. For in vitro diagnostic use only.

The Diayzme D-Dimer Assay Calibrator Set is intended for use in the calibration of the D-Dimer assay only. For in vitro diagnostic use only.

The Diazyme D-Dimer Assay Control Set is intended for use as quality controls for the Diazyme D-Dimer assay only. For in vitro diagnostic use only.

Prescription Use X (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 Device Evaluation and Safety (OVD)

Lenk L. L.

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

K112120 510(k)

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