(132 days)
The Dade Behring Stratus® CS D-dimer method is an in vitro diagnostic test intended for use with the Stratus® CS fluorometric analyzer for the determination of cross-linked fibrin degradation products (D-dimer) in plasma.
The Dade Behring Stratus® CS D-dimer TestPak method is an enzyme-linked fluorescent immunoassay that consists of a five(5)- well, plastic cartridge (TestPak) designed for use only on the Dade Behring Stratus® CS fluorometric analyzer. Within the TestPak cartridge is a small square of embedded glass fiber paper. Reagents and sample are added through an opening onto the glass fiber paper. Following incubation, the enzyme-labeled antibody and the bound D-dimer fraction react. The enzymatic rate of the bound fraction increases with the concentration of the D-dimer in the sample and is measured via fluorescence. Dilutions, if needed, may be accomplished via utilization of the Stratus®CS DilPak (diluent) cartridges. All data analysis functions are performed automatically by the analyzer.
Here's an analysis of the provided text, focusing on the acceptance criteria and the study that proves the device meets those criteria:
Device: Dade Behring Stratus® CS D-dimer method
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in a formal, enumerated list. Instead, the demonstration of equivalence relies on comparing performance characteristics with a predicate device. The primary performance metric presented is the correlation between the new device and the predicate.
| Acceptance Criteria (Inferred from Predicate Comparison) | Reported Device Performance (Dade Behring Stratus® CS D-dimer Method) |
|---|---|
| Strong correlation with predicate device | Correlation Coefficient: 0.923 (compared to bioMerieux Vitek VIDAS® D-dimer Assay) |
| Slope close to 1.0 when compared to predicate device | Slope: 0.995 (compared to bioMerieux Vitek VIDAS® D-dimer Assay) |
| Minimal intercept when compared to predicate device | Intercept: 159 ng/mL (compared to bioMerieux Vitek VIDAS® D-dimer Assay) |
| Comparable intended use | In vitro diagnostic test for the quantitative measurement of cross-linked fibrin degradation products (D-dimer) in human citrated or heparinized plasma. |
| Comparable technological design | Automated Fluorescent immunoassay; 450nm; Alkaline phosphatase = conjugate; 4-methylumbelliferyl phosphate = substrate. |
| Comparable assay range | 6 - 5000 ng/mL (Predicate: 45 - 1000 ng/mL, the Stratus CS has a wider reported range, which is generally considered an improvement or acceptable difference if analytical performance holds.) |
| Comparable sample type | Whole blood/plasma (Predicate: plasma. The Stratus CS accepts whole blood/plasma, implying an acceptable difference or broader utility.) |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size: n = 123 clinical patient samples.
- Data Provenance: The samples were "clinical patient samples" and were tested at Dade Behring (Glasgow, Delaware), USA. The text does not explicitly state if the study was retrospective or prospective, but the phrasing "clinical patient samples were tested" typically implies these were existing samples, making it likely a retrospective analysis of previously collected samples.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This is an in vitro diagnostic device for measuring a biomarker in blood. The ground truth for such devices is typically established by:
- The results from a well-established, legally marketed predicate device (as is the case here).
- Reference methods or highly accurate laboratory techniques.
The concept of "experts" in the sense of clinicians or radiologists interpreting images is not applicable here. The "ground truth" for the performance comparison is the result obtained from the bioMerieux Vitek VIDAS® D-dimer Assay.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. This is a comparison of two quantitative laboratory assays. Adjudication methods involving multiple human readers are used for diagnostic imaging or subjective assessments, not for objective biomarker measurements. The "adjudication" in this context is the direct comparison of the numerical results from the two devices.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is not an AI-assisted diagnostic imaging device or one that involves human interpretation of results in the way an MRMC study would apply. It's a laboratory assay.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in a way. The "Dade Behring Stratus® CS D-dimer method" and the "bioMerieux Vitek VIDAS® D-dimer Assay" are both automated systems that perform the measurement and data analysis without human intervention in the result generation. The comparison performed ("split sample comparison") assesses the standalone performance of the new device against the predicate device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for comparison was the results obtained from a legally marketed predicate device, specifically the bioMerieux Vitek VIDAS® D-dimer Assay (K973819). The new device's performance was evaluated based on how closely its measurements correlated with those of the predicate device.
8. The sample size for the training set
The document does not explicitly mention a separate "training set" or its size for the development of the Dade Behring Stratus® CS D-dimer method. For in vitro diagnostic assays, the development often involves iterative optimization and calibration using various reagent lots and known concentration samples, rather than a distinct "training set" in the machine learning sense. The validation of the device's performance is demonstrated through the comparative study described.
9. How the ground truth for the training set was established
As no specific "training set" is described, this question is not fully applicable. However, the foundational "ground truth" for developing such an assay would typically be established using:
- Reference materials/calibrators: Samples with precisely known D-dimer concentrations.
- Established analytical methods: High-precision laboratory techniques to determine true concentrations during development.
The continuous calibration process mentioned ("Calibration curve updated for each lot, using one level (triplicate) and every 60 days, thereafter") indicates an ongoing internal "ground truthing" process for each manufactured lot.
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1022976
JAN 1 6 2003
Summary of Safety and Effectiveness Information
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: | Richard M. VaughtDade Behring Inc.P.O. Box 6101Newark, DE 19714-6101 |
|---|---|
| Date of Preparation: | September 4, 2002 |
| Name of Product: | Dade Behring Stratus® CS D-dimer method; includes separatelysupplied TestPak (assay) and DilPak (diluent) |
| FDA Classification Name: | Fibrinogen/fibrin degradation products assay |
| Predicate Device: | bioMerieux Vitek VIDAS® D-dimer Assay (K973819) |
| Device Description: | The Dade Behring Stratus® CS D-dimer TestPak method is an enzyme-linked fluorescent immunoassay that consists of a five(5)- well, plastic cartridge (TestPak) designed for use only on the Dade Behring Stratus® CS fluorometric analyzer. Within the TestPak cartridge is a small square of embedded glass fiber paper. Reagents and sample are added through an opening onto the glass fiber paper. Following incubation, the enzyme-labeled antibody and the bound D-dimer fraction react. The enzymatic rate of the bound fraction increases with the concentration of the D-dimer in the sample and is measured via fluorescence. Dilutions, if needed, may be accomplished via utilization of the Stratus®CS DilPak |
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(diluent) cartridges. All data analysis functions are performed automatically by the analyzer. The Dade Behring Stratus® CS D-dimer method is an in vitro Intended Use: diagnostic test for the quantitative measurement of cross-linked fibrin degradation products (D-dimer) in human citrated or heparinized plasma. The Stratus® CS D-dimer method is substantially equivalent Comparison to Predicate Device: in technological design and intended use to other D-dimer assays such as the bioMerieux Vitek VIDAS® D-dimer assay (K973819). A comparison of the features of these products is provided below:
| Feature | Dade Behring Stratus® CSD-dimer Method | bioMerieux Vitek VIDAS®D-dimer Assay |
|---|---|---|
| Intended Use: | in vitro use | in vitro use |
| Technology: | AutomatedFluorescent immunoassay; 450nmAlkaline phosphatase = conjugate4-methylumbelliferyl phosphate = substrate | AutomatedFluorescent immunoassay; 450 nmAlkaline phosphatase = conjugate4-methylumbelliferyl phosphate = substrate |
| Sample: | whole blood/plasma | plasma |
| Sample volume: | 75 uL | 200 uL |
| Assay range: | 6 - 5000 ng/mL | 45 - 1000 ng/mL |
| Calibration: | Calibration curve updated for each lot,using one level (triplicate) and every60 days, thereafter. After calibrationupdate at completion of each test, recoveredvalues are calculated from stored calibrationcoefficients. | One point calibrator tested (duplicate) with eachlot initially and every 14 days, thereafter. |
Comments on Substantial Equivalence:
Split sample comparison with citrated human plasma samples between the Stratus® D-dimer method and the VIDAS® D-dimer (DD) assay gave a correlation coefficient of 0.923, a slope of 0.995 and an intercept of 159 ng/mL. In this study, clinical patient
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samples (n = 123) were tested at Dade Behring (Glasgow, Delaware) and ranged from 79 ng/mL to 5689 ng/mL as tested on the VIDAS® D-dimer assay.
Conclusion:
The Dade Behring Stratus® CS D-dimer (DDMR) method and the bioMerieux Vitek VIDAS® Ddimer (DD) assay are substantially equivalent in intended use, technological design and specific performance characteristics, including split sample comparison results as noted above.
KimVaught
Richard M. Vaught Regulatory Affairs and Compliance Manager September 4, 2002
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle with three heads, representing the department's mission to protect the health of all Americans and provide essential human services.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Richard M. Vaught Regulatory Affairs and Compliance Manager Dade Behring, Inc. Glasgow Site, Bldg. 500, Box 514 P.O. Box 6101 Newark, Delaware 19714-6101
JAN 1 6 2003
K022976 Re:
Trade/Device Name: Stratus® CS D-dimer (DDMR) Method Regulation Number: 21 CFR § 864.7320 Regulation Name: Fibrin Degradation Products Regulatory Class: II Product Code: DAP Dated: December 18, 2002 Received: December 20, 2002
Dear Mr. Vaught:
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 (301) 594-3084. 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 (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely vours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications For Use Statement
Device Name:
Stratus® CS D-dimer (DDMR) Method
Indications for Use:
The Dade Behring Stratus® CS D-dimer method is an in vitro diagnostic test intended for use with the Stratus® CS fluorometric analyzer for the determination of cross-linked fibrin degradation products (D-dimer) in plasma.
Rmplinight
chard M. Vaught Regulatory Affairs and Compliance Manager
September 4, 2002
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Jacchini Bautista
(Division Sin-Off)
Division of clinical Laboratory Devices
510(k) Number K022976
Prescription Use (Per 21 CFR 801.109)
OR
Over-the-counter Use
(Optional format 1-2-96)
§ 864.7320 Fibrinogen/fibrin degradation products assay.
(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).