VIDAS® D-Dimer Exclusion II™ is an automated quantitative test for use on the instruments of the VIDAS family for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate, CTAD) using the ELFA technique (Enzyme Linked Fluorescent Assay). VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

Device Description

The VIDAS® D-Dimer Exclusion II assay is an automated quantitative test for use on the instruments of the VIDAS family for the determination of fibrin degradation products (FbDP) in human plasma (sodium citrate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

The assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. The assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). The individual kit components are described in detail on the following pages.

All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times.

First, the sample is taken by the SPR, diluted and then cycled in and out of the SPR several times. The antigen binds to the anti-FbDP immunodobulins coated on the SPR. Unbound components are eliminated during a washing step. In the second step, the conjugate that contains an alkaline phosphatase labeled anti-FbDP monoclonal antibody is cvcled in and out of the SPR to form a sandwich. Unbound components are eliminated during the washing steps.

A detection step is then performed. The substrate (4-Methyl-umbellifery) phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone), the fluorescence of which is measured at 450 nm. The intensity of fluorescence is proportional to the concentration of antigen present in the sample. At the end of the assay, results are automatically calculated by the instrument in relation to the calibration curve stored in memory. The results are then printed.

AI/ML Overview

Acceptance Criteria and Study for VIDAS® D-Dimer Exclusion II Assay

This analysis focuses on the information provided in the 510(k) Summary for the VIDAS® D-Dimer Exclusion II Assay (K112818).

1. Table of Acceptance Criteria and Reported Device Performance

The provided document primarily focuses on demonstrating substantial equivalence to a predicate device rather than explicitly stating acceptance criteria for new device performance. However, by comparing the VIDAS® D-Dimer Exclusion II (DEX2) with its predicate (VIDAS® D-Dimer Exclusion), we can infer the performance metrics that were deemed acceptable for the new device. The "reported device performance" are the values presented for the VIDAS® D-Dimer Exclusion II Assay.

Metric	Acceptance Criteria (Inferred from Predicate)	Reported Device Performance (VIDAS® D-Dimer Exclusion II)
Intended Use	Exclusion of DVT & PE in outpatients with pretest probability model	Exclusion of DVT & PE in outpatients with pretest probability model
Assay Technique	ELFA	ELFA
Automated	Yes	Yes
Assay Duration	Similar to or improved from 35 min, 35 sec	19 minutes, 57 seconds (Improved)
SPR Coating	Anti-FbDP monoclonal mouse antibodies	Anti-FbDP monoclonal mouse antibodies (No preservative)
Calibration Frequency	Improved from 14 days	28 days (Improved)
Sample Type	Citrated plasma	Citrated or CTAD plasma (Expanded)
Assay Range	45-10,000 ng/mL	45-10,000 ng/mL
Clinical Cut-Off	500 ng/mL	500 ng/mL
Linearity	45-5,000 ng/mL	45-10,000 ng/mL (Improved)
Detection Limit	≤ 45 ng/mL	≤ 45 ng/mL
Hook Effect	400,000 ng/mL	400,000 ng/mL
Specificity (Fibrinogen)	No cross-reactivity	<10 g/L (No cross-reactivity)
Specificity (FbDP X)	No cross-reactivity	<10 µg/mL (No cross-reactivity)
Specificity (FbDP Y)	No cross-reactivity	<10 µg/mL (No cross-reactivity)
Specificity (FbDP D)	Cross-reactivity (10-100 µg/mL), but not clinically significant in target population	Cross-reactivity (10-100 µg/mL), but not clinically significant in target population
Total Precision (CV)	< 7.1% at various concentrations	CV 6.6 % at 277.97 ng/mL CV 5.9 % at 544.14 ng/mL CV 6.0% at 7,788.88 ng/mL
Interference (Hemoglobin)	No interference up to 300 µmol/L	No interference up to 300 µmol/L
Interference (Lipemia)	No interference up to 20 g/L	No interference up to 30 g/L (Improved)
Interference (Bilirubin)	No interference up to 537 µmol/L	No interference up to 537 µmol/L
Interference (Rheumatoid Factor)	No interference up to 396 IU/mL	No interference up to 400 IU/mL (Slightly improved)
Drug Interference	N/A (Predicate did not perform separate study)	47 analytes tested, no interference observed
Normal Values	96% less than 500 ng/mL	90% less than 500 ng/mL

Note on Acceptance Criteria: The document is a 510(k) summary for substantial equivalence. The "acceptance criteria" are not explicitly stated as quantitative thresholds but are implicitly met by demonstrating that the new device's performance is either equivalent to or improved compared to the predicate device across various analytical and clinical characteristics. For instance, if the predicate had a linearity range of X, and the new device has a linearity range of Y (where Y >= X), then Y would be considered acceptable. The "Normal Values" for DEX2 (90% less than 500 ng/mL) is slightly lower than the predicate (96%), but in the context of a qualitative D-Dimer Exclusion assay where values below the cut-off are considered negative, this might still be deemed acceptable if the overall clinical sensitivity and specificity for DVT/PE exclusion remain robust.

2. Sample Size Used for the Test Set and Data Provenance

The document states "A summary of the non-clinical results is presented in the table below," referring to the detailed comparison table. This table includes analytical performance data.

Sample Size for Test Set: The specific sample sizes for each analytical performance test (e.g., linearity, precision, interference, specificity) are not provided in this summary. The table indicates values for these tests (e.g., CV at specific ng/mL levels), implying that tests were conducted, but the number of samples or replicates used for each test is not detailed.
Data Provenance: Not explicitly stated. Given that bioMérieux, Inc. is the submitter (located in Hazelwood, MO, USA), the studies were likely conducted in the USA or through their global facilities. The summary does not specify whether the data is retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This is a an in vitro diagnostic device measuring D-Dimer levels. For such devices, "ground truth" for analytical performance studies is typically established by:

Reference Methods: Comparing the new assay's results against established reference methods or highly accurate laboratory techniques.
Reference Materials: Using certified reference materials or plasma samples with known D-Dimer concentrations.
Clinical Diagnosis: For clinical performance, the ground truth for DVT/PE would be established by definitive diagnostic imaging (e.g., ultrasonography, CTPA) and/or medical record review, not by "experts" in the sense of adjudicating images.

The summary does not mention any "experts" being used to establish ground truth for the analytical test set in the way one would for diagnostic imaging. Instead, the performance is compared to the predicate device and established analytical methodologies.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are primarily used in studies involving subjective interpretation, often in imaging or clinical assessments where multiple readers provide opinions, and inconsistencies need resolution.

Since the VIDAS® D-Dimer Exclusion II Assay is an automated quantitative immunoassay, the results are numerical and objective. Therefore, an adjudication method in the sense of resolving conflicting interpretations is not applicable to the analytical performance tests described in this summary. The "results are automatically calculated by the instrument," which minimizes the need for human adjudication of raw data.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. An MRMC comparative effectiveness study is not mentioned. Such studies are typically conducted for diagnostic imaging devices where human readers interpret medical images, and the AI's impact on their performance is assessed. The VIDAS® D-Dimer Exclusion II Assay is an in vitro diagnostic device, and its performance is assessed analytically and clinically, not through human-in-the-loop image interpretation.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, in essence. The VIDAS® D-Dimer Exclusion II is an automated assay. Its "performance" as described (assay range, linearity, precision, specificity, etc.) is the standalone performance of the instrument and reagents. The results are automatically calculated by the instrument.

However, it's crucial to note that the device's intended use is "in conjunction with a clinical pretest probability assessment model." This means that while the assay itself is standalone, its clinical utility for DVT/PE exclusion requires human interpretation of the assay result combined with a clinical pretest probability assessment. The output of the device (D-Dimer concentration) is an algorithmic result, but its application in patient management involves a human clinician.

7. The Type of Ground Truth Used

For the analytical performance characteristics summarized, the ground truth would be established by:

Reference Standards/Materials: For linearity, detection limit, hook effect, and precision, samples with known, precisely measured concentrations of D-Dimer or related substances are used.
Interference Substances: Known concentrations of interfering substances (e.g., hemoglobin, bilirubin, rheumatoid factor, drugs) are added to samples to determine their impact.
Reference Assays: For method comparison (implicitly to the predicate, and typically to other established D-Dimer assays), results are compared against those from a recognized reference method.

For the stated Intended Use (exclusion of DVT/PE in outpatients), the ultimate ground truth in clinical studies (which are not detailed in this analytical performance summary but are foundational for such devices) would be definitive clinical diagnosis of DVT or PE, typically established by objective imaging studies (e.g., compression ultrasonography for DVT, CT Pulmonary Angiography for PE) and clinical follow-up. This summary focuses on the analytical performance, not the full clinical validation study details.

8. The Sample Size for the Training Set

This document is a 510(k) summary for an immunoassay, not a machine learning or AI-based device that would typically have a separate "training set" for an algorithm. The "training set" concept is not applicable here in the conventional AI/ML sense.

For an immunoassay, the "training" equivalent would be the extensive R&D and validation work done to optimize reagent concentrations, incubation times, antibody selection, and assay parameters. This process would involve many experiments with various sample types and concentrations, but it's not described as a discrete "training set" like in AI.

9. How the Ground Truth for the Training Set Was Established

As noted above, the concept of a "training set" in the AI/ML context with an established ground truth is not applicable to this immunoassay. The development and optimization of the assay would rely on:

Biochemical Principles: Understanding antigen-antibody reactions, enzyme kinetics, and fluorescent detection.
Calibrators and Controls: Precisely manufactured substances with known concentrations, used to establish the calibration curve and monitor assay performance.
Validation Studies: Iterative experiments using a wide range of patient samples (with D-dimer levels determined by reference methods or clinical diagnosis) to optimize and verify performance characteristics like sensitivity, specificity, and linearity.

These activities during the assay development process serve a similar function to a training set in that they guide the refinement of the assay, but the specifics are not detailed in this regulatory summary.

Summary

{0}------------------------------------------------

K112818

JUL 3 1 2012

VIDAS® D-Dimer Exclusion II Assay

Traditional 510(k) Submission

Image /page/0/Picture/4 description: The image shows the logo for bioMérieux. The logo consists of a circle that is divided into two halves, with the left half having horizontal lines and the right half being solid black. The text "BIOMÉRIEUX" is written in all caps below the circle.

510(k) Summary

July 12, 2012

510(k) SUMMARY

VIDAS® D-Dimer Exclusion II Assay

A. Submitter Information

Submitter's Name: bioMérieux, Inc.

II.	Address:	595 Anglum RoadHazelwood, MO 63042
	Contact Person:	John Albright
	Phone Number:	314-731-8546
	Fax Number:	314-731-8689
	Date of Preparation:	September 2011
	B. Device NameTrade Name:	VIDAS® D-Dimer Exclusion II Assay
	Common Name:	D-Dimer Exclusion II Assay
	Classification Name:	21 CFR 864.7320 Product Code DAPFibrinogen/fibrin degradation products assay

C. Predicate Device Name Trade Name:

VIDAS® D-Dimer Exclusion Assay

D. Device Description

All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times.

{1}------------------------------------------------

BIME REETIX

, l

Traditional 510(k) Submission

510(k) Summarv

E. Intended Use

VIDAS® D-Dimer Exclusion II™ is an automated quantitative test for use on the instruments of the VIDAS family for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate, CTAD) using the ELFA technique (Enzyme Linked Fluorescent Assay). VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical probability assessment model to exclude deep yein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

F. Technological Characteristics Summary

A general comparison of the similarities and differences of the current assay, VIDAS D-Dimer Exclusion II (ref. 30445) and the predicate assay VIDAS D-Dimer Exclusion (K040882) ref. 30442 is presented in the table below.

{2}------------------------------------------------

Image /page/2/Picture/0 description: The image shows the logo for bioMerieux. The logo consists of a circle that is half black and half white with vertical lines. The text "BIO M É RIE U X" is below the circle.

Traditional 510(k) Submission

510(k) Summary

III.Item	VIDAS® D-Dimer Exclusion II Assay	VIDAS® D-Dimer Exclusion Assay(K040882) - Predicate
General Comparison
Intended Use	VIDAS® D-Dimer Exclusion II™ is anautomated quantitative test for use onthe instruments of the VIDAS family forthe immunoenzymatic determination offibrin degradation products (FbDP) inhuman plasma (sodium citrate) usingthe ELFA technique (Enzyme LinkedFluorescent Assay). VIDAS D-DimerExclusion II is indicated for use inconjunction with a clinical pretestprobability assessment model toexclude deep vein thrombosis (DVT)and pulmonary embolism (PE) diseasein outpatients suspected of DVT or PE.	VIDAS D-Dimer Exclusion is anautomated quantitative test for use onthe VIDAS instruments for theImmunoenzymatic determination offibrin degradation products (FbDP) inhuman plasma (sodium citrate) usingthe ELFA technique (Enzyme-LinkedFluorescent Assay). VIDAS D-DimerExclusion is indicated for use inconjunction with a clinical pretestprobability assessment model toexclude deep vein thrombosis (DVT)and pulmonary embolism (PE)disease in outpatients suspected ofDVT or PE.
Assay Technique	Enzyme-linked fluorescent assay(ELFA)	Enzyme-linked fluorescent assay(ELFA)
Automated	Yes	Yes
Assay Duration	19 minutes, 57 seconds	35 minutes, 35 seconds
SPR	Coating solution includes Anti-FbDPmonoclonal mouse antibodiesNo preservative	Coating solution includes Anti-FbDPmonoclonal mouse antibodiesBuffer preservative=azide
Strip	Conjugate includes alkalinephosphatase-labeled anti-FbDPmonoclonal immunoglobulins (mouse)MIT or MIT + BND (Wells 5-9 replacedsodium azide with MIT or MIT+ BND).Sodium azide only remains in well 10.Conjugate buffer containsNon specific Purified mouse IgG*Nonirradiated de-complemented horse	Conjugate includes alkalinephosphatase-labeled anti-FbDPmonoclonal immunoglobulins (mouse)Preservative = azide (Wells 5-10contain sodium.azide as thepreservative)Conjugate buffer containsNon specific Mouse ascite Tg180Conjugate buffer includes de-complimented irradiated or non
Calibrators andControlsApproximatetarget (ng/mL)	serumS1: 3000-3500S2=N/AC1 : 5200-6040C2 : 250-380Allows reconstitution with water	irradiated horse serumS1 : 3700-4400S2 : 420-580C1 : 4200-4800C2 : 380-520Reconstituted with the R1 diluentincluded in the kit
	Recalibration frequency=28 days	Recalibration frequency=14 days
Sample type	Citrated or CTAD plasma	Citrated plasma
Analytical Performance Comparison
IV.	Item	VIDAS® D-Dimer Exclusion II Assay	VIDAS® D-Dimer Exclusion Assay (K040882) - Predicate
	Assay range	45-10,000 ng/mL	45-10,000 ng/mL
	Clinical Cut Off	500 ng/mL	500 ng/mL
	Linearity	45-10,000 ng/mL	45-5,000 ng/mL
	Detection Limit	≤ 45 ng/mL	≤ 45 ng/mL
	Hook Effect	400,000 ng/mL	400,000 ng/mL
Specificity	Fibrinogen (<10 g/L)	No cross reactivity
	Fibrinogen degradation products X (<10 µg/mL)		No cross reactivity for fibrinogen or fibrinogen degradation products X, Y and D
	Fibrinogen degradation products Y (<10 µg/mL )
	Fibrinogen degradation products D (10 - 100 µg/mL)	Cross reactivity between 10-100 µg/mL; however such high levels of fibrinogen degradation products D do not occur in the target population of suspected VTE patients
Total Precision (CV)		CV 6.6 % at 277.97 ng/mLCV 5.9 % at 544.14 ng/mLCV 6.0% at 7,788.88 ng/mL	CV 5.7 % at 264 ng/mLCV 5.8% at 549 ng/mLCV 7.1% at 7283 ng/mL
Interference		No interference withHemoglobin up to 300 µmol/LLipemia up to 30 g/LBilirubinemia up to 537 µmol/LRheumatoid factor: up to 400 IU/mLHuman albumin: up to 60 g/L	No interference withHemoglobin up to 300µmol/LLipemia up to 20 g/LBilirubin up to 537µmol/LRheumatoid 396 IU/mL
Drug Interference		47 analytes were tested and no interference was observed	Not performed
Normal Values		90% less than 500 ng/mL	96% less than 500 ng/mL
Method Comparison		D-Dimer Exclusion (K040882) vs. D-Dimer Exclusion II	N/A

{3}------------------------------------------------

Image /page/3/Picture/1 description: The image shows the logo for bioMérieux. The logo consists of a circle that is half black and half striped, with the company name "BIOMÉRIEUX" written below it. A thin, curved line runs vertically through the center of the circle and the company name.

Traditional 510(k) Submission

510(k) Summary

G. Performance Data

A summary of the non-clinical results is presented in the table below.

{4}------------------------------------------------

Image /page/4/Picture/1 description: The image shows the logo for bioMerieux. The logo consists of the word "BIOMERIEUX" in all caps, with a stylized image above it. The image is a circle that is half black and half with vertical lines, with a thin vertical line extending above and below the circle.

Traditional 510(k) Submission

H. Conclusion

The VIDAS® D-Dimer Exclusion II Assay is substantially equivalent to the bioMerieux VIDAS D-Dimer Exclusion Assay.

The 510(k) summary includes only information that is also covered in the body of the 510(k). The summary does not contain any puffery or unsubstantiated labeling claims. The summary does not contain any raw data, i.e., contains only summary data. The summary does not contain any trade secret or confidential commercial information. The summary does not contain any patient identification information.

{5}------------------------------------------------

Image /page/5/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" arranged around the perimeter. Inside the circle is a stylized image of an eagle or other bird with outstretched wings, rendered in a simple, graphic style.

10903 New Hampshire Avenue Silver Spring, MD 20993

bioMerieux, Inc. c/o Ms. VeRonica Daenzer Sr. Regulatory Affairs Specialist 595 Anglum Road Hazelwood, MO 63042-2320

JUL 3 1 2012

Re: K112818

Trade/Device Name: VIDAS® D-Dimer Exclusion IITM (DEX2) Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/fibrin degradation products assay Regulatory Class: Class II Product Code: DAP Dated: July 30, 2012 Received: July 31, 2012

Dear Ms Daenzer:

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 class II (Special Controls), 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

{6}------------------------------------------------

Page 2 - Ms. VeRonica Daenzer

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); 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Reena Philip

on Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{7}------------------------------------------------

Indications for Use

510(k) Number (if known):___K112818

Device Name: VIDAS® D-Dimer Exclusion II Assay

Indications For Use:

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 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)

Division Sign-Off

Office of In-Vitro Diagnostic Device Evaluation and Safety

510(k) K112818

Page 1 of 1

Regulation Number and Section

§ 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).