HemosIL D-Dimer HS is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude venous thromboembolism (VTE) in outpatients suspected of deep venous thrombosis (DVT) and pulmonary embolism (PE).

For in vitro diagnostic use.

Device Description

The D-Dimer HS Latex Reagent is a suspension of polystyrene latex particles of uniform size coated with the F(ab')2 fragment of a monoclonal antibody highly specific for the D-Dimer domain included in fibrin soluble derivatives. The use of the F(ab')2 fragment allows a more specific D-Dimer detection avoiding the interference of some endogenous factors like the Rheumatoid Factor. When a plasma containing D-Dimer is mixed with the Latex Reagent and the Reaction Buffer included in the D-Dimer HS kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of D-Dimer in the sample and is determined by measuring the decrease of the transmitted light caused by the aggregates (turbidimetric immunoassay).

AI/ML Overview

This document is a 510(k) summary for the HemosIL D-Dimer HS device, which is an in vitro diagnostic (IVD) test. This specific submission (K160885) is a "Special 510(k)" to update the Limit of Detection (LoD) claim for the device.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Key Takeaway: The "device" in this context is an in vitro diagnostic assay (HemosIL D-Dimer HS) used to quantitatively determine D-Dimer levels in human plasma. The primary focus of this specific 510(k) submission is to update a performance claim, specifically the Limit of Detection (LoD), rather than introducing a new product or a significant change in intended use.

Given this, the questions provided in the prompt, which are commonly associated with AI/ML-driven medical imaging devices, need to be reinterpreted or noted as "not applicable" for this type of IVD 510(k) submission.

Acceptance Criteria and Reported Device Performance

The core acceptance criterion for this submission is the updated Limit of Detection (LoD). The device's performance is reported directly against this criterion.

1. Table of acceptance criteria and the reported device performance:

Acceptance Criterion	Original Claim (Predicate)	Updated Claim (Proposed/Reported Performance)
Limit of Detection (LoD)	21 ng/mL	137 ng/mL

Note: The submission states that the only change is to the LoD claim based on additional testing. All other performance claims (linearity, cut-off, etc.) remain the same as the predicate device.

Study Details (Reinterpreted for IVD Context)

Many of the points in the prompt are more relevant to AI/ML image analysis rather than an IVD assay. Where applicable, the information is provided. Where not applicable, it is noted.

2. Sample size used for the test set and the data provenance:

Sample Size: The document states that the testing was "additional testing done to current CLSI EP17-A2 requirements" to establish the updated LoD. However, the specific number of samples (e.g., patient samples, spiked samples, replicates) used for this testing to calculate the LoD is not provided in this summary. CLSI EP17-A2 is a standard guideline for evaluation of detection capability for clinical laboratory measurement procedures. This guideline typically involves a statistically significant number of replicates (e.g., 20 or more) of blank/low-level samples across multiple runs.
Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given it's an in vitro diagnostic, samples would typically be analyzed fresh or from appropriately stored biobanks.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not Applicable in this context. For an IVD assay like D-Dimer, the "ground truth" for the test set is established by the known concentrations of calibrators and controls, or by reference methods/materials of traceable value (e.g., a known concentration of D-Dimer in a sample matrix). It does not involve human expert interpretation in the same way an imaging study would.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

Not Applicable. This concept is for diagnostic interpretation, typically by human readers, not for quantitative analytical performance of an IVD assay.

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 an IVD assay, not an AI-assisted diagnostic imaging system. Its performance is measured analytically (e.g., precision, accuracy, LoD, linearity) against known values or reference methods, not against human reader performance.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Yes, in the context of an IVD. The HemosIL D-Dimer HS device is an automated, standalone assay run on ACL TOP instruments. Its performance (e.g., LoD) is determined analytically by the instrument and reagents, independent of human interpretive input. Human operators load samples and reagents, and review results, but the analytical measurement itself is automated.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

For an analytical performance evaluation like Limit of Detection, the ground truth is established based on statistical analysis of replicate measurements of samples with very low (or zero) analyte concentration. This would involve:
- Defined Calibrators: Solutions with known, precise concentrations of D-Dimer.
- Controls: Materials with target D-Dimer concentrations used for quality control.
- Reference Materials/Methods: Comparison to a highly accurate reference method or certified reference materials, if available, though for LoD, it's more about statistical confidence in detecting low levels.
- Statistical Methods: LoD is determined using statistical approaches defined by guidelines like CLSI EP17-A2, which typically involves measuring blank samples and low-level samples and calculating the concentration at which detection is statistically reliable. This does not involve "expert consensus" in the clinical diagnostic sense.

8. The sample size for the training set:

Not Applicable in the AI/ML sense. This is not an AI/ML algorithm that requires a "training set." The assay is a chemical and immunoturbidimetric reaction. The development of such an assay involves extensive R&D and optimization, but not typically a "training set" in the machine learning paradigm.

9. How the ground truth for the training set was established:

Not Applicable. See point 8. The "ground truth" for developing the assay itself involves ensuring the reagents specifically bind to D-Dimer and that the turbidimetric measurement accurately correlates with its concentration. This is achieved through chemical and biological validation, not through annotated training data.

Summary

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

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an emblem featuring a stylized representation of three human profiles facing to the right, stacked one behind the other.

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

October 27, 2016

Instrumentation Laboratory Co. Ms. Carol Marble Regulatory Affairs Director 180 Hartwell Road Bedford, MA 01730

Re: K160885

Trade/Device Name: HemosIL D-Dimer HS Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/fibrin degradation products assay Regulatory Class: Class II Product Code: DAP Dated: September 28, 2016 Received: September 29, 2016

Dear Ms. Marble:

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

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

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.

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

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

Indications for Use

510(k) Number (if known) K160885

Device Name HemosIL D-Dimer HS

Indications for Use (Describe)

For in vitro diagnostic use.

Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

Image /page/3/Picture/0 description: The image shows the logo for Instrumentation Laboratory, a Werfen Company. The logo consists of a stylized graphic element in shades of blue and green, resembling overlapping shapes. To the right of the graphic is the company name, "Instrumentation Laboratory," in a clear, sans-serif font. Below the company name is the tagline "A Werfen Company" in a smaller font size.

510(k) Summary

This 510(k) Summary is being submitted in accordance with the requirements of 21 CER 807.92 and the Safe Medical Device Act of 1990.

Submission Type	Special 510(k)
Submitter's Information	Instrumentation Laboratory (IL) Co.180 Hartwell RoadBedford, MA 01730, USA
Contact Person	Carol Marble, Regulatory Affairs DirectorPhone: 781-861-4467Fax: 781-861-4207Email: cmarble@ilww.com
Preparation Date	September 28, 2016
Device Trade Name	HemosIL D-Dimer HS
Regulatory Information	Classification:Regulation No.:Common Name:Panel:Product Code:	Class II21 CFR 864.7320Fibrinogen and Fibrin split products, Antigen, Antiserum, ControlHematology (81)DAP
Predicate Device	HemosIL D-Dimer HS	510(k) No.: K151534
Device Description	The D-Dimer HS Latex Reagent is a suspension of polystyrene latexparticles of uniform size coated with the F(ab')2 fragment of amonoclonal antibody highly specific for the D-Dimer domainincluded in fibrin soluble derivatives. The use of the F(ab')2fragment allows a more specific D-Dimer detection avoiding theinterference of some endogenous factors like the RheumatoidFactor. When a plasma containing D-Dimer is mixed with the LatexReagent and the Reaction Buffer included in the D-Dimer HS kit, thecoated latex particles agglutinate. The degree of agglutination isdirectly proportional to the concentration of D-Dimer in the sampleand is determined by measuring the decrease of the transmittedlight caused by the aggregates (turbidimetric immunoassay).
Device Indications for Use	HemosIL D-Dimer HS is an automated latex enhancedimmunoassay for the quantitative determination of D-Dimer inhuman citrated plasma on the ACL TOP for use in conjunctionwith a clinical pretest probability (PTP) assessment model toexclude venous thromboembolism (VTE) in outpatients suspectedof deep venous thrombosis (DVT) and pulmonary embolism (PE).

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

Description of the Modification	The Limit of Detection (LoD) claim in the HemosIL D-Dimer HSinsert sheet is being updated as follows based on additionaltesting done to current CLSI EP17-A2 requirements.
Current LoD Claim: 21 ng/mL	Updated LoD Claim: 137 ng/mL

Reason Submission Qualifiesas Special 510(k)	The submission meets the criteria for a Special 510(k) based on thefollowing:
	• No change in indications for use or intended use
	• No change in operating principle
	• No change to labeled performance claims, except for the LoDclaim based on an additional study
	• No change to stability claims or to storage instructions
	• No change to reagent preparation
	• No change to specimen collection and preparation
	• No change to formulation or materials
	• No change to data reduction software
	• No change to test parameters
	• No change to calibration

	The verification testing to establish the updated Limit of Detection(LoD) claim for the HemosIL D-Dimer HS assay was conducted underdesign control and in accordance with CLSI EP17-A2.
Design Control Activities	Per the Risk Management Report, the proposed change to the LoDclaim does not introduce any additional risk and has no impact onthe safety or effectiveness of the currently marketed device.

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

Comparison to Predicate:

Similarities
Item	Predicate (K151534)	Modified Device
Intended Use	HemosIL D-Dimer HS is an automated latexenhanced immunoassay for the quantitativedetermination of D-Dimer in human citratedplasma on the ACL TOP Family and ACL TOPFamily 50 Series for use, in conjunction with aclinical pretest probability (PTP) assessmentmodel to exclude venous thromboembolism(VTE) in outpatients suspected of deepvenous thrombosis (DVT) and pulmonaryembolism (PE).	Same
Analyte	D-Dimer	Same
Methodology	Latex-enhanced immuoturbidimetric assay	Same
ClaimedAnalyzers	ACL TOP Family:ACL TOP 300 CTS ACL TOP 500 CTS ACL TOP 700 ACL TOP 700 CTS ACL TOP 700 LAS ACL TOP Family 50 Series: ACL TOP 350 CTS ACL TOP 550 CTS ACL TOP 750 ACL TOP 750 CTS ACL TOP 750 LAS	Same
Sample Type	Citrated Plasma	Same
Cut-off	230 ng/mL	Same
Linearity	150 – 69000 ng/mL	Same
Differences
Detection Limit	21 ng/mL	137 ng/mL

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).