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-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

AI/ML Overview

This document, K151534, is a 510(k) premarket notification for the HemosIL D-Dimer HS device. The submission is a "Special 510(k)" to add information about the association of patient age with D-Dimer levels to the device's insert sheet. This means there are no changes to the device's performance, indications for use, or operating principles. Therefore, there is no new study conducted to demonstrate that the device meets new acceptance criteria. Instead, the focus is on the substantial equivalence to the predicate device (K070927) based on the absence of changes to performance claims.

Given that this is a Special 510(k) submission for minor labeling changes and explicitly states "No change to labeled performance claims", there isn't a new study presented in this document proving the device meets new acceptance criteria. The existing performance acceptance criteria and their proof are derived from the original clearance of the predicate device (K070927).

However, I can extract the reported performance of the device (which remains unchanged from the predicate) and details relevant to a typical device submission, even though a new study isn't detailed here for new acceptance criteria.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a Special 510(k) for labeling changes, the acceptance criteria and reported performance are implicitly those established during the original clearance of the predicate device (K070927). The document explicitly states "No change to labeled performance claims."

Acceptance Criteria	Reported Device Performance
Indications for Use	Automated latex enhanced immunoassay for quantitative determination of D-Dimer in human citrated plasma on ACL TOP, for use with clinical pretest probability (PTP) assessment model to exclude VTE in outpatients suspected of DVT and PE.
Analyte	D-Dimer
Methodology	Latex-enhanced immunoturbidimetric assay
Analyzers	ACL TOP Family
Sample Type	Citrated Plasma
Cut-off	230 ng/mL
Linearity	150 – 69000 ng/mL
Detection Limit	21 ng/mL
Performance Claims	No change to labeled performance claims from predicate (K070927)

2. Sample size used for the test set and the data provenance
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
4. Adjudication method for the test set
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
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
8. The sample size for the training set
9. How the ground truth for the training set was established

The provided document (K151534) is a Special 510(k) submission that does not include a new study to establish performance for the device. It states, "No change to labeled performance claims, including no change to the assay cut-off." This submission is solely to add general information to the device's insert sheet regarding the association of patient age with D-Dimer levels, citing "peer-reviewed published literature."

Therefore, the information requested in points 2-9 about test sets, experts, adjudication, MRMC studies, standalone performance, ground truth, and training sets is not available in this document. Such details would have been part of the original 510(k) submission (K070927) for the predicate device, which established its performance characteristics. This current submission does not involve new clinical or performance studies for the device itself.

Summary

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

July 6, 2015

INSTRUMENTATION LABORATORY CO. NIKITA MALLADI REGULATORY AFFAIRS SPECIALIST 180 HARTWELL ROAD BEDFORD, MA 01730

Re: K151534

Trade/Device Name: HemosIL D-Dimer HS Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/fibrin degradation products assay Regulatory Class: II Product Code: DAP Dated: June 5, 2015 Received: June 8, 2015

Dear Ms. Malladi:

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 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

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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 regulations (21 CFR Parts 801 and 809), 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" (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 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)

K151534

Device Name HemosIL D-Dimer HS

Indications for Use (Describe)

Hemos!L 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.

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)

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510(k) Summary

The submission meets the criteria for a Special 510(k) under the FDA guidance "The New 510(k) Paradigm -Alternate Approaches to Demonstrating Substantial Equivalence in Premarket Notifications".

Submitter's Information	Instrumentation Laboratory (IL) Co.180 Hartwell RoadBedford, MA 01730, USA
Contact Person	Nikita Malladi, Regulatory Affairs Specialist IIPhone: 781-674-3245Fax: 781-861-4207Email: nmalladi@ilww.com
Preparation Date	June 5, 2015
Device Trade Name	HemosIL D-Dimer HS
Regulatory Information	Classification: Class IIRegulation No.: 21 CFR 864.7320Common Name: Fibrinogen and Fibrin split products, Antigen, Antiserum, ControlPanel: Hematology (81)Product Code: DAP
Predicate Device	HemosIL D-Dimer HS 510(k) No.: K070927
Device Indications for Use /Intended Use	HemosIL D-Dimer HS is an automated latex enhanced immunoassayfor the quantitative determination of D-Dimer in human citratedplasma on the ACL TOP for use in conjunction with a clinical pretestprobability (PTP) assessment model to exclude venousthromboembolism (VTE) in outpatients suspected of deep venousthrombosis (DVT) and pulmonary embolism (PE)For in vitro diagnostic use.
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 transmitted

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Comparison to Predicate:

This Special 510(k) is being submitted to add general information from peer-reviewed published literature to the Summary and Principle section of the HemoslL D-Dimer HS insert sheet regarding the association of patient age with D-Dimer levels.

The submission meets the criteria for a Special 510(k) based on the following:

No change in indications for use or intended use
No change in operating principle
No change to labeled performance claims, including no change to the assay cut-off ●
. 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
. No change to quality controls

Following is a description of the similarities and differences between the currently marketed HemosIL D-Dimer HS (K070927) and HemosIL D-Dimer HS with the insert sheet modifications:

Similarities
Item	Predicate (K070927)	Modified Device
Indications for Use	HemosIL D-Dimer HS is an automatedlatex enhanced immunoassay for thequantitative determination of D-Dimerin human citrated plasma on the ACLTOP Family for use in conjunction with aclinical pretest probability(PTP)assessment model to exclude venousthromboembolism (VTE) in outpatientssuspected of deep venous thrombosis(DVT) and pulmonary embolism (PE).	Same
Analyte	D-Dimer	Same
Methodology	Latex-enhanced immuoturbidimetricassay	Same
Analyzers	ACL TOP Family	Same
Sample Type	Citrated Plasma	Same
Cut-off	230 ng/mL	Same
Linearity	150 – 69000 ng/mL	Same
Detection Limit	21 ng/mL	Same
Performance Claims	No change to labeled performance claims	Same

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Comparison to Predicate (Cont.):

Differences
Item	Predicate (K070927)	Modified Device
Insert SheetSummary and PrincipleSection	Current insert language:Elevated levels of D-Dimer arefound in clinical conditions suchas deep vein thrombosis (DVT),pulmonary embolism (PE) anddisseminated intravascularcoagulation (DIC).D-Dimer levels also rise duringthe normal pregnancy, but veryhigh levels are associated withcomplications.	Insert revisions in italic :Elevated levels of D-Dimer arefound in clinical conditions such asdeep vein thrombosis (DVT),pulmonary embolism (PE) anddisseminated intravascularcoagulation (DIC).D-Dimer levels also rise with age,and during the normal pregnancy,but very high levels are associatedwith complications.Further, age-adjusted cut-off valuesfor DVT and PE suspicion have beenshown to increase the specificity ofD-Dimer and reduce the number ofunnecessary imaging studies inpatient populations greater than 50years.NOTE: Bibliography in insertupdated with applicablesupporting references.

Conclusion:

HemosIL D-Dimer HS, with the modified Summary and Principle insert section, is substantially equivalent to the legally marketed predicate device FDA cleared under K070927.

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).