(422 days)
The Diazyme Fibrinogen Assay is for the quantitative determination of fibrinogen levels in citrated human plasma. For in vitro diagnostic use only.
The Diazyne Fibringen Calibrator Set is intended for use in the Diazyme Fibrinogen Assay. For in vitro diagnostic use only.
The Diazyme Fibringen Control Set is intended for use as quality controls for the Diazyme Fibrinogen Assay. For in vitro diagnostic use only.
The performance of this device has not been established in neonate and pediatric patient populations.
Diazyme Fibrinogen Assay System consists of the following items:
-
- The Diazyme Fibrinogen Assay: containing reagent R1 and reagent R2. Reagent 1 contains buffer, saline, and sodium azide. Reagent 2 containing anti-human fibrinogen Ig fraction tittered to optimal concentrations dependent on sera lot and sodium azide.
-
- Diazyme Fibrinogen Calibrator Set: 3 levels, serum based, intended for use in the calibration of the Diazyme Fibrinogen Assay. The calibrators are in lyophilized form containing purified human fibrinogen antigen, defibrinated human serum and sodium azide
-
- Diazyme Fibrinogen Control Set: 2 levels, serum based, intended for use as quality controls for the Diazyme Fibrinogen Assay. The controls are in lyophilized form containing purified human fibrinogen antigen, defibrinated human serum and sodium azide.
The Diazyme Fibrinogen Assay is run on Roche Modular P analyzer (K953239/005). The Diazyme Fibrinogen Assay never comes into direct contact with patient's venous blood sample is first collected by a phlebotomist and then submitted for determination of fibrinogen concentration using Diazyme Fibrinogen Assay by trained professionals.
The Control Unit of the Roche Modular P analyzer uses a graphical interface to control all instrument functions. The computer, keyboard, and touchscreen monitor allows users to navigate through the software, enter assay, calibrator, and control information, and make test selections. The Diazyme Fibrinogen Modular P application parameters provided are programmed into the Modular P analyzers. The reagents, calibrators and controls are loaded into the analyzer. The Roche Modular P stores the Diazyme Fibrinogen Assay reagents in a refrigerated compartment. Reagent and sample pipettes automatically aspirate and dispense specified amounts of reagent or calibrators, controls, and sample into reaction cells. The change in absorbance is measured at specified wavelengths.
After a 4-point calibration, spline-fitting is used to smoothly fit polynomial functions through mean values of the response for calibrators of known concentrations. The Roche Modular P calculates the fibrinogen concentration of a patient sample by interpolation of the obtained signal to a stored 4-point calibration curve.
This document describes the Diazyme Fibrinogen Assay and compares its performance characteristics to a predicate device, the Kamiya K-Assay Fibrinogen (K993482), to demonstrate substantial equivalence.
Here's the breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate, pre-defined set of values that the device met. Instead, it presents performance characteristics and then concludes "Performance data and risk analysis indicates that differences should not affect the safety and effectiveness of the Diazyme Fibrinogen Assay and offers users an in vitro diagnostic device system to measure fibrinogen in human plasma," implicitly suggesting these performance levels are acceptable for substantial equivalence.
Here's a comparison of the Diazyme Fibrinogen Assay's performance against the predicate:
| Performance Characteristic | Predicate (Kamiya K-Assay Fibrinogen) | Subject Device (Diazyme Fibrinogen Assay) | Equivalency Statement |
|---|---|---|---|
| Assay/Linear Range | 100 – 900 mg/dL | 100 – 900 mg/dL | Similar |
| Precision (CV%) | 1.8 – 13.0% | Less than 10% (Specifically, total CVs were 5-7% for samples, 6-8% for calibrators, 2-3% for controls across various studies) | Similar |
| Accuracy (Correlation to Predicate) | Correlation Coefficient (R²) = 0.990 (vs Incstar ITA) | Correlation Coefficient (R²) = 0.9946 (vs. Kamiya K-Assay) | Similar |
| Accuracy (Slope) | 0.967 (vs Incstar ITA) | 0.986 (vs. Kamiya K-Assay) | Similar |
| Accuracy (Y-Intercept) | 33.91 (vs Incstar ITA) | 2.72 (vs. Kamiya K-Assay) | Similar |
| Reagent Composition | R1: Buffer R2: Anti-human fibrinogen goat antiserum Calibrator: Lyophilized | R1: Phosphate buffered saline R2: Goat anti-human Fibrinogen reagent Calibrators: Lyophilized | Same |
| Calibrator Set | 1 x 1.0 mL Single-Level Calibrator | 1 x 1.0 mL Calibrator 1, 1 x 1.0 mL Calibrator 2, 1 x 1.0 mL Calibrator 3 | Different |
| Control Set | 5 x 1.0mL Control 1, 5 x 1.0mL Control 2 (plasma based) | 1 x 1.0mL Control 1, 1 x 1.0mL Control 2 (serum based) | Similar |
2. Sample Size Used for the Test Set and Data Provenance
- Precision (Sample Repeatability): 6 citrated plasma samples. Tested over 10 days, 2 runs/day, 2 replicates/run = 240 measurements per sample type.
- Precision (Calibrator Repeatability): 3 levels of calibrators. Tested over 10 days, 2 runs/day, 2 replicates/run = 360 measurements per calibrator level.
- Precision (Control Repeatability): 2 levels of controls. Tested over 20 days, 2 runs/day, 2 replicates/run = 160 measurements per control level.
- Reproducibility (Multi-site precision): 6 citrated plasma samples, 3 calibrator levels, 2 control levels. Plasma: 60 measurements per sample (implies 3 sites, but not explicitly stated how many measurements per site). Calibrator/Control: 120 measurements per level.
- Linearity: An eleven-level linearity set prepared by mixing a pooled fibrinogen spiked plasma sample and saline at different proportions.
- Method Comparison: A total of 176 human plasma samples.
- Interference: Not specified as a specific "test set" size, but various interferents were tested at specified concentrations.
Data Provenance:
The document does not explicitly state the country of origin of the samples. For precision, linearity, and interference, it implies in-house testing by Diazyme Laboratories. For method comparison, it states "Human plasma samples" from "3 clinical sites," but the location of these sites and whether the data is retrospective or prospective is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not provided in the document. For in vitro diagnostic devices like this, the "ground truth" for method comparison is typically established by results from the predicate device itself, or in some cases, a well-established reference method. There is no mention of experts establishing a ground truth for individual samples.
4. Adjudication Method for the Test Set
This information is not applicable/provided. For analytical performance studies of quantitative IVD assays, an adjudication method (like 2+1 expert consensus) is typically not used in the same way it would be for qualitative image-based diagnostic systems. The reference method (predicate device) provides the comparative "truth."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging interpretation where human readers are involved. The Diazyme Fibrinogen Assay is an in vitro diagnostic assay run on an automated analyzer (Roche Modular P), not a system designed for human interpretation.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the performance studies described (Precision, Linearity, Method Comparison, Interference) are all standalone performance evaluations of the Diazyme Fibrinogen Assay device itself, without human-in-the-loop performance measurement. The device runs on an automated analyzer (Roche Modular P), and its performance is assessed against established analytical performance metrics and comparison to a predicate device.
7. The Type of Ground Truth Used
For the method comparison study, the predicate device's results (Kamiya K-Assay Fibrinogen) served as the comparative "ground truth" or reference method. For linearity, it was prepared standards. For precision, the "truth" is the statistical mean of repeated measurements.
8. The Sample Size for the Training Set
This information is not applicable/provided. The Diazyme Fibrinogen Assay is an immunoturbidimetric assay based on chemical reactions and optical measurements, not a machine learning or AI-based device that would typically involve a "training set" in the computational sense. The "training" of the assay involves establishing calibration curves using known calibrator concentrations.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable/provided. As above, the device is not an AI/ML system requiring a training set with "ground truth" labels. Calibration curves are established using the "Diazyme Fibrinogen Calibrator Set," which contains purified human fibrinogen antigen at known concentrations. These known concentrations serve as the basis for the instrument to interpret sample results.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 31, 2016
Diazyme Laboratories Abhijit Datta, Ph.D. Director, Technical Operations 12889 Gregg Court Poway, CA 92064
Re: K143470
Trade/Device Name: Diazyme Fibrinogen Assay Diazyme Fibrinogen Calibrator Set Diazyme Fibrinogen Control Set Regulation Number: 21 CFR 864.7340 Regulation Name: Fibrinogen determination system Regulatory Class: Class II Product Code: GIS, GFX, GIL Dated: January 15, 2016 Received: January 19, 2016
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
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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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set 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 contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Leonthena R. Carrington -S
Leonthena R. Carrington, MS, MBA, MT(ASCP) 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) K143470
Device Name
Diazyme Fibrinogen Assay; Diazyme Fibrinogen Calibrator Set; Diazyme Fibrinogen Control Set
Indications for Use (Describe)
The Diazyme Fibrinogen Assay is for the quantitative determination of fibrinogen levels in citrated human plasma. For in vitro diagnostic use only.
The Diazyne Fibringen Calibrator Set is intended for use in the Diazyme Fibrinogen Assay. For in vitro diagnostic use only.
The Diazyme Fibringen Control Set is intended for use as quality controls for the Diazyme Fibrinogen Assay. For in vitro diagnostic use only.
The performance of this device has not been established in neonate and pediatric patient populations.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
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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 |
|---|---|
| Submitter's address: | 12889 Gregg CourtPoway, CA 92064USA |
| Name of Contact Person: | Dr. Abhijit DattaDiazyme Laboratories12889 Gregg CourtPoway, CA 92064Phone: 858-455-4762Fax: 858-455-2120 |
| Date the Summary was Prepared: | January 15, 2016 |
| Name of the Device | Diazyme Fibrinogen AssayDiazyme Fibrinogen Calibrator SetDiazyme Fibrinogen Control Set |
| Trade Name: | Diazyme Fibrinogen AssayDiazyme Fibrinogen Calibrator SetDiazyme Fibrinogen Control Set |
| Common/Usual Name | Diazyme Fibrinogen Assay |
| Device Classification Name | Fibrinogen, Antigen, Antiserum, Control, Calibrator |
| Product code: | GIS, Fibrinogen Determination SystemGFX, Fibrinogen StandardGIL, Plasma, Fibrinogen Control |
| Panel: | Hematology |
| Submission Type | Traditional 510k |
| Regulation Number | 21CFR 864.7340 Fibrinogen determination system |
| Device Class | Class II |
| Predicate Device: | Kamiya K-Assay Fibrinogen (K993482) |
| Manufacturing Address | Diazyme Laboratories |
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12889 Gregg Court Poway, CA 92064 USA
Establishment Registration 2032900
DESCRIPTION OF THE DEVICE
Clinical Significance
Fibrinogen is a ~340 kDa plasma glycoprotein essential to blood clot formation. In the final step of the coagulation cascade, thrombin cleaves fibrinogen to form insoluble fibrin monomers, which then polymerize to form fibrin clots.
Abnormal plasma fibrinogen quality or quantity can occur as inherited or acquired disorders. Higher levels of fibrinogen are associated with inflammation, trauma, surgery, and pregnancy. A decrease of the fibrinogen level is observed in disseminated intravascular coagulation (DIC), fibrinolysis and hereditary diseases. Additionally, fibrinogen is an acute phase reactant, thus upregulated during inflammation or tissue damage.
Assay Principle
The Diazyme Fibrinogen Assay is based on an immunoturbidimetric assay. Fibrinogen in plasma binds to specific anti-fibrinogen antibody and forms immune complexes. The degree of turbidity caused by immune complexes can be measured optically at 340nm, and is proportional to the quantity of fibrinogen in the sample. The instrument calculates the fibrinogen concentration by interpolation of obtained signal of a 4-point calibration curve prepared from calibrators of known concentrations.
Detailed Device Description
Diazyme Fibrinogen Assay System consists of the following items:
-
- The Diazyme Fibrinogen Assay: containing reagent R1 and reagent R2. Reagent 1 contains buffer, saline, and sodium azide. Reagent 2 containing anti-human fibrinogen Ig fraction tittered to optimal concentrations dependent on sera lot and sodium azide.
-
- Diazyme Fibrinogen Calibrator Set: 3 levels, serum based, intended for use in the calibration of the Diazyme Fibrinogen Assay. The calibrators are in lyophilized form containing purified human fibrinogen antigen, defibrinated human serum and sodium azide
-
- Diazyme Fibrinogen Control Set: 2 levels, serum based, intended for use as quality controls for the Diazyme Fibrinogen Assay. The controls are in lyophilized form containing purified human fibrinogen antigen, defibrinated human serum and sodium azide.
The Diazyme Fibrinogen Assay is run on Roche Modular P analyzer (K953239/005). The Diazyme Fibrinogen Assay never comes into direct contact with patient's venous
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blood sample is first collected by a phlebotomist and then submitted for determination of fibrinogen concentration using Diazyme Fibrinogen Assay by trained professionals.
The Control Unit of the Roche Modular P analyzer uses a graphical interface to control all instrument functions. The computer, keyboard, and touchscreen monitor allows users to navigate through the software, enter assay, calibrator, and control information, and make test selections. The Diazyme Fibrinogen Modular P application parameters provided are programmed into the Modular P analyzers. The reagents, calibrators and controls are loaded into the analyzer. The Roche Modular P stores the Diazyme Fibrinogen Assay reagents in a refrigerated compartment. Reagent and sample pipettes automatically aspirate and dispense specified amounts of reagent or calibrators, controls, and sample into reaction cells. The change in absorbance is measured at specified wavelengths.
See Reaction Scheme.
Image /page/6/Figure/3 description: The image shows a timeline of a chemical reaction. At time 0, 200 microliters of R1 and 6 microliters of sample are added. After some time at 37 degrees Celsius, 50 microliters of R2 are added at 5 minutes. At 6 minutes, A1 is measured at 340 nm, and at 10 minutes, A2 is measured.
After a 4-point calibration, spline-fitting is used to smoothly fit polynomial functions through mean values of the response for calibrators of known concentrations. The Roche Modular P calculates the fibrinogen concentration of a patient sample by interpolation of the obtained signal to a stored 4-point calibration curve.
#: The Modular P analyzer performs automatic on-board 1: 20 dilution using saline (5 uL + 100 uL saline).
Use the provided Diazyme Fibrinogen Assay (DZ768A) Application Parameters for Roche Modular P and enter the application parameters via the keyboard, settings sheet or barcode sheet, as appropriate.
| Modular P Applications | |
|---|---|
| Measuring mode | Absorbance |
| Abs. calculation mode | 2 Point END |
| Reaction mode | S-R1/R3 |
| Reaction direction | Increase |
| Primary/Secondary Wavelength | 340 nm/700nm |
| Calc. first/last | 18/34 |
| Unit | mg/dL |
| Pipetting parameters | |
| R1 | 200 µL |
| Sample | 5 µL |
| Sample diluent (saline) | 100 µL (1:20 dilution |
| Diluted Sample | 6 µL |
| R2 | 50 µL |
| Total volume | 256 µL |
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Indications for Use:
The Diazyme Fibrinogen Assay is for the quantitative determination of fibrinogen levels in citrated human plasma. For in vitro diagnostic use only.
The Diazyme Fibrinogen Calibrator Set is intended for use in the calibration of the Diazyme Fibrinogen Assay. For in vitro diagnostic use only.
The Diazyme Fibrinogen Control Set is intended for use as quality controls for the Diazyme Fibrinogen Assay. For in vitro diagnostic use only.
Performance Characteristics of Subject Device
Precision
The precision of the Diazyme Fibrinogen Assay was evaluated according to CLSI EP5-A2 guideline. In the study, 6 citrated plasma samples including one sample close to the very low end of the AMR and one sample close to the very high end of the AMR were tested with three lots of reagents. The results are summarized in the following table:
| Sample | N | Meanmg/dL | Within-Run(SD, %CV) | Between-Run(SD, %CV) | Between-Lot(SD, %CV) | Between-Day(SD, %CV) | Total(SD, %CV) |
|---|---|---|---|---|---|---|---|
| Plasma 1 | 240 | 453.4 | 8.0, 2% | 9.4, 2% | 16.2, 4% | 10.6, 2% | 23.0, 5% |
| Plasma 2 | 240 | 333.4 | 5.8, 2% | 5.2, 2% | 10.7, 3% | 7.4, 2% | 15.1, 5% |
| Plasma 3 | 240 | 208.6 | 3.0, 1% | 3.2, 2% | 6.6, 3% | 4.9, 2% | 9.3, 5% |
| Plasma 4 | 240 | 107.3 | 1.6, 2% | 1.7, 2% | 3.6, 3% | 2.8, 3% | 5.2, 5% |
| Plasma 5 | 240 | 706.8 | 11.9, 2% | 13.9, 2% | 27.1, 4% | 20.1, 3% | 38.4, 5% |
| Plasma 6 | 240 | 823.9 | 16.3, 2% | 12.7, 2% | 30.3, 4% | 22.3, 3% | 42.9, 5% |
Sample Repeatability (Three Reagent Lots Combined)
Additionally, three lots of the calibrators were tested for precision using three lots of the reagents calibrated with master lot of the calibrators. The calibrators were tested 2 runs per day over 10 working days.
Calibrator Repeatability (Three Reagent Lots and Three Calibrator Lots Combined)
| Calibrator | N | Mean | Within-Run(SD, %CV) | Between-Run(SD, %CV) | Between-Lot(SD, %CV) | Between-Day(SD, %CV) | Total(SD, %CV) |
|---|---|---|---|---|---|---|---|
| Level 1 | 360 | 262 | 5.7,2% | 0,0% | 13.3,5% | 12.1,5% | 18.8,7% |
| Level 2 | 360 | 578 | 17.9,3% | 0,0% | 27.9,5% | 22.5,4% | 40.1,7% |
| Level 3 | 360 | 1130 | 21.2,2% | 0,0% | 44.9,4% | 40.4,4% | 64.0,6% |
Two lots of serum based controls were tested in duplicates per run, 2 runs per day for 20 days using two lots of the reagents.
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| Sample | Mean(N=160) | Within-Run | Between-Run | Between-Lot | Between-Day | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
| Level 1 | 173.2 | 2.3 | 1 | 1.4 | 1 | 4.1 | 2 | 3.1 | 2 | 4.1 | 2 |
| Level 2 | 607.5 | 8.2 | 1 | 6.5 | 1 | 15.1 | 3 | 11.1 | 2 | 15.2 | 3 |
Control Repeatability (Two Reagent Lots and One Control Lot Combined)
Multi-site precision (reproducibility) study was performed at two external sites and Diazyme site on Modular P analyzer. In this study, the same sets of 6 citrated plasma samples as used. Six citrated plasma including one sample close to the very low end of the AMR and one sample close to the high end of the AMR were tested. The results of the within-run, between-run, between-day, between-site and total CV% are listed in the following tables
Reproducibility Data Analysis (Three Sites, Three Calibrator and Control Lots combined)
| Sample | N | Mean | With-in | Between run | Between day | Between Site | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| mg/dL | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
| Plasma 1 | 60 | 408.5 | 10.2 | 3% | 8.8 | 2% | 27.5 | 7% | 29.9 | 7.3% | 42.8 | 10% |
| Plasma 2 | 60 | 303.1 | 6.2 | 2% | 2.3 | 1% | 21.1 | 7% | 21.6 | 7.1% | 30.9 | 10% |
| Plasma 3 | 60 | 195.5 | 2.9 | 2% | 1.8 | 1% | 9.6 | 5% | 9.9 | 5.1% | 14.2 | 7% |
| Plasma 4 | 60 | 100.0 | 1.2 | 1% | 1.1 | 1% | 5.0 | 5% | 5.1 | 5.1% | 7.4 | 7% |
| Plasma 5 | 60 | 701.5 | 22.4 | 3% | 23.8 | 3% | 29.9 | 4% | 43.9 | 6.2% | 62.2 | 9% |
| Plasma 6 | 60 | 818.4 | 13.6 | 2% | 7.7 | 1% | 9.1 | 1% | 18.0 | 2.2% | 25.5 | 3% |
| Calibrator1 | 120 | 250.7 | 3.8 | 2% | 6.0 | 2% | 11.7 | 5% | 13.6 | 5.4% | 19.3 | 8% |
| Calibrator2 | 120 | 502.1 | 11.0 | 2% | 10.9 | 2% | 14.0 | 3% | 20.8 | 4.1% | 29.5 | 6% |
| Calibrator3 | 120 | 1077.3 | 17.1 | 2% | 14.9 | 1% | 47.0 | 4% | 51.8 | 4.8% | 73.5 | 7% |
| Control 1 | 120 | 179.4 | 3.2 | 2% | 1.9 | 1% | 6.1 | 3% | 7.1 | 4.0% | 10.0 | 6% |
| Control 2 | 120 | 609.6 | 13.2 | 2% | 12.6 | 2% | 16.4 | 3% | 24.4 | 4.0% | 34.6 | 6% |
Linearity
The eleven levels linearity set was prepared by mixing a pooled fibrinogen spiked plasma sample containing 1000 mg/dL fibrinogen and saline at different proportions according to Clinical and Laboratory Standards Institute EP6-A. The results showed that Diazyme Fibrinogen Assay is linear up to 1032.8 mg/dL. Based on linearity data. method comparison data, and limit of quantitation (LOQ = 12.9 mg/dL) study, and reference interval study, and predicate AMR, the analytical measuring range (AMR) of Diazyme Fibrinogen assay is claimed to be 100-900 mg/dL.
Method Comparison
Human plasma samples were tested with the Diazyme Fibrinogen Assay and the obtained results were compared to the predicate method according to CLSI EP9-A2 guideline. A total of 176 samples tested across 3 clinical sites. All samples were tested in singlet with both methods. The results are summarized in the following table:
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| Parameter | Regular Regression | Deming regression |
|---|---|---|
| n | 176 | 176 |
| Slope | 0.986 | 0.989 |
| 95% CI | 0.975 – 0.997 | 0.978 – 0.999 |
| Intercept | 2.72 | 1.80 |
| 95% CI | -1.70 - 7.13 | -2.68 - 6.22 |
| Standard Error of Estimate | 15.31 | 15.32 |
| Correlation Coefficient(R) | 0.9973 | 0.9973 |
| Sample Range (Diazyme) | 107.5 - 870.0 | 107.5 - 870.0 |
Interference
The following substances normally present in the plasma produced less than 10% deviation when tested at levels equal to the concentrations listed below, according to CLIA EP7-A "Interference Testing in Clinical Chemistry".
The following endogenous substances do not interfere with this assay at the levels tested (less than 10% bias).
| Interferent | Concentration | |
|---|---|---|
| Ascorbic Acid | 176 mg/dL | |
| Bilirubin | 40 mg/dL | |
| Bilirubin Conjugated | 40 mg/dL | |
| Hemoglobin | 1000 mg/dL | |
| Rheumatoid Factor | 220 IU/ml | |
| Triglycerides | 1000 mg/dL |
The common therapeutic substances of Acetylsalicyclic Acid, Na2-Cefoxitin, Ibuprofen, fibrin degradation product and coagulation inhibitors such as warfarin, dabigatran, hirudin, rivaroxaban, and argatroban, heparin showed no significant interference (< ± 10%) up to the concentrations summarized below.
| Interferent | Concentration |
|---|---|
| Acetylsalicylic Acid | 2.78 mM |
| Na2-Cefoxitin | 1554 μM |
| Ibuprofen | 2438 μM |
| Warfarin | 65 μM |
| Dabigatran | 3.7 µg/mL |
| Hirudin | 25 µg/mL |
| Rivaroxaban | 7.0 µg/mL |
| Argatroban | 20.0 µg/mL |
| FDP | 0.5 mg/mL |
| Unfractionated Heparin | 3000 U/L |
| Low molecular weight Heparin | 3000 U/L |
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Summary of the Performance Characteristics of the subject Device in Comparison of the Predicate Device
| Kamiya K-Assay Fibrinogen(K993482) | Diazyme Fibrinogen Assay | Equivalency |
|---|---|---|
| Assay Range: 100 – 900 mg/dL | Linear Range: 100 – 900 mg/dL | |
| Precision: CV% of 1.8 – 13.0% | Precision: CV of less than 10% | |
| Accuracy (vs Incstar ITA):Correlation Coefficient ( $R²$ ) = 0.990Slope = 0.967y-intercept = 33.91 | Accuracy (vs. Kamiya K-Assay ):Correlation Coefficient ( $R²$ ) = 0.9946Slope = 0.986y-intercept = 2.72 | Similar |
Summary of Assay Kit Components Comparing to the predicate device
| Kamiya K-Assay Fibrinogen(K993482) | Diazyme Fibrinogen Assay | Equivalency |
|---|---|---|
| Reagent 1: Buffer ReagentTris(hydroxymethyl)aminomethane(100mM), ready to useReagent 2: Antiserum ReagentAnti-human fibrinogen goat antiserumCalibrator:Lyophilized calibrator | Reagent 1Phosphate buffered saline solution,ready to useReagent 2Goat anti-human Fibrinogenreagent, ready to useCalibratorsLyophilized calibrators preparedwith serum, purified humanFibrinogen, and 0.09% sodiumazide | Same |
| Calibrator Set | Calibrator Set | |
| 1 x 1.0 mL Single-Level Calibrator | 1 x 1.0 mL Calibrator 11 x 1.0 mL Calibrator 21 x 1.0 mL Calibrator 3 | Different |
| Control Set (plasma based) | Control Set (serum based) | |
| 5 x 1.0mL Control 15 x 1.0mL Control 2 | 1 x 1.0mL Control 11 x 1.0mL Control 2 | Similar |
Rationale for Considering the Device Substantially Equivalent to Devices Approved for Inter-State Commerce
Kamiya K-Assay was selected for method comparison with Diazyme Fibrinogen Assay. The reagents used for the Diazyme Fibrinogen Assay are similar to the predicate and used to develop the application for the Roche Modular P analyzer. The design, key materials, and chemical composition are similar between subject device and predicate device. The method comparison study between the subject and predicate using clinical patient samples showed excellent
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correlation. The similarities and differences between the predicate reagent and the Diazyme Fibrinogen Assay are given in the table above. Detailed performance characteristics and comparison analysis are given in the filing and demonstrate substantial equivalence to predicate device.
The performance characteristics of the Diazyme Fibrinogen Assay are substantially similar to that of the approved predicate test. Performance data and risk analysis indicates that differences should not affect the safety and effectiveness of the Diazyme Fibrinogen Assay and offers users an in vitro diagnostic device system to measure fibrinogen in human plasma.
Conclusion
Detailed method comparison analysis (accuracy studies) presented in this 510k submission, together with linearity, precision and interference studies, demonstrates that the Diazyme Fibrinogen Assay performance is acceptable, safe and effective. There is no significant deviation between the results obtained by Diazyme Fibrinogen Assay and the legally marketed predicate device Kamiya K-Assay Fibrinogen (K993482) when testing clinical patient samples and is thus substantially similar.
§ 864.7340 Fibrinogen determination system.
(a)
Identification. A fibrinogen determination system is a device that consists of the instruments, reagents, standards, and controls used to determine the fibrinogen levels in disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot).(b)
Classification. Class II (special controls). A control or fibrinogen standard intended for use with a fibrinogen determination system is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.