HemosIL D-Dimer HS 500 is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP® Family and ACL TOP Family 50 Series Systems 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 500 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 HemosIL D-Dimer HS 500 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 transmitted light caused by the aggregates (turbidimetric immunoassay).

AI/ML Overview

The provided document is a 510(k) summary for the HemosIL D-Dimer HS 500 device. This particular submission (K172903) is a Special 510(k), meaning it's for modifications to an already cleared device (predicate K090264) and not for a de novo clearance. Special 510(k)s typically do not require new clinical studies to demonstrate device performance against acceptance criteria, as the performance claims are carried over from the predicate device.

The main purpose of K172903 is to add general information from peer-reviewed published literature to the Summary and Principle section of the HemosIL D-Dimer HS 500 insert sheet regarding the association of patient age with D-Dimer levels and to clarify that the device's performance has not been validated for age-adjusted cut-off values.

Therefore, many of the requested items regarding a new clinical study and ground truth establishment would not be applicable to this specific submission. However, I can extract the acceptance criteria and performance claims that apply to the predicate device and are carried over to this modified device.

Here's the breakdown based on the provided text:

1. A table of acceptance criteria and the reported device performance

Since this is a Special 510(k) for an insert sheet modification and not a new device, the acceptance criteria and reported performance are implicitly the same as the predicate (K090264). The document explicitly states "No change to labeled performance claims, including no change to the assay cut-off."

Performance Criterion	Acceptance Criteria (from predicate K090264)	Reported Device Performance (for K172903, same as predicate)
Cut-off	500 ng/mL	500 ng/mL
Linearity	215 - 128000 ng/mL	215 - 128000 ng/mL
Detection Limit	203 ng/mL	203 ng/mL
Indications for Use	Automated latex enhanced immunoassay for quantitative determination of D-Dimer in human citrated plasma on ACL TOP Family and ACL TOP Family 50 Series Systems for use, in conjunction with a clinical pretest probability (PTP) assessment model to exclude VTE in outpatients suspected of DVT and PE.	Same as predicate.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

This information is not provided in this Special 510(k) summary (K172903) because no new clinical test set was used or presented for this particular submission. The performance claims are based on the predicate device (K090264). To obtain this information, one would need to refer to the 510(k) summary for K090264.

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 information is not provided in this Special 510(k) summary (K172903) as no new clinical test set (requiring expert ground truth) was used for this submission. This type of detail would be found in the original 510(k) for the predicate device (K090264) which established the clinical performance.

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

This information is not provided in this Special 510(k) summary (K172903) as no new clinical test set requiring adjudication was used for this submission. This type of detail would be found in the original 510(k) for the predicate device (K090264).

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

This device is an in vitro diagnostic for D-Dimer measurement, not an imaging device typically analyzed by human readers in the context of MRMC studies or AI assistance in reading. Therefore, an MRMC comparative effectiveness study, as described, is not applicable.

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

The HemosIL D-Dimer HS 500 is an automated immunoassay for quantitative determination. Its performance is inherently "standalone" in the sense that it provides a quantitative result based on the immunoassay reaction, without direct human cognitive input in interpreting the raw signal for the D-Dimer concentration. The result is then used in conjunction with a clinical pretest probability (PTP) assessment model by a clinician. The validation of its quantitative accuracy would have been performed during the original clearance (K090264).

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

For an in vitro diagnostic device like a D-Dimer assay, the ground truth for performance measures like linearity, detection limit, and cut-off would typically be established by:

Reference methods/calibrators: For analytical performance (linearity, detection limit), certified reference materials or highly accurate reference methods would be used.
Clinical outcomes/diagnosis: For the diagnostic performance (sensitivity, specificity, NPV for VTE exclusion), the ground truth for DVT/PE would be established through definitive diagnostic imaging (e.g., ultrasound, CTPA, ventilation-perfusion scan) or other established clinical diagnostic criteria for the patient cohort recruited for the original predicate study (K090264).

This specific Special 510(k) (K172903) does not provide these details as it relies on the predicate (K090264).

8. The sample size for the training set

This information is not provided in this Special 510(k) summary (K172903). For an immunoassay, the concept of a "training set" in the context of machine learning (as often implied by this question) is not directly applicable. However, method development and optimization would involve numerous samples, with calibration curves and reagents being "trained" or optimized during the development phase of the original predicate device (K090264), but described in terms of analytical validation rather than a machine learning 'training set'.

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

As above, while not a "training set" in the common AI sense, the ground truth for optimizing assay parameters and establishing analytical performance (for the original predicate K090264) would have been established using reference standards or established, validated methods. Clinical training data, if any, for setting the original cut-off would have involved patients with confirmed (or ruled out) DVT/PE, as validated by definitive diagnostic tests. This information is not within this K172903 document.

Summary

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

November 22, 2017

Instrumentation Laboratory Co. Shajunath Nirupama Regulatory Affairs Specialist I 180 Hartwell Road Bedford, MA 01730

Re: K172903

Trade/Device Name: HemosIL D-Dimer HS 500 Regulation Number: 21 CFR 864.7320 Regulation Name: Fibrinogen/fibrin degradation products assay Regulatory Class: Class II Product Code: DAP Dated: October 26, 2017 Received: October 27, 2017

Dear Ms. Nirupama:

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

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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

Lea Carrington 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) K172903

Device Name

HemosIL, D-Dimer HS 500

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)

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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	Shajunath Nirupama,Regulatory Affairs Specialist IPhone: 781-861-4083Fax: 781-861-4207Email: snirupama@ilww.com
Preparation Date	November 17, 2017
Device Trade Name	HemosIL D-Dimer HS 500
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 500 510(k) No: K090264
Device Indications for Use /Intended Use	HemosIL D-Dimer HS 500 is an automated latex enhancedimmunoassay for the quantitative determination of D-Dimer inhuman citrated plasma on the ACL TOP® Family and ACL TOP Family50 Series Systems 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 500 Latex Reagent is a suspension of polystyrenelatex particles 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')2 fragmentallows a more specific D-Dimer detection avoiding the interferenceof some endogenous factors like the Rheumatoid Factor. When aplasma containing D-Dimer is mixed with the Latex Reagent and theReaction Buffer included in the HemosIL D-Dimer HS 500 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 transmitted lightcaused by the aggregates (turbidimetric immunoassay).

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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 HemosIL D-Dimer HS 500 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:

ん No change in indications for use or intended use
Σ No change in operating principle
Σ No change to labeled performance claims, including no change to the assay cut-off
と No change to stability claims or to storage instructions
Σ No change to reagent preparation
ル No change to specimen collection and preparation
2 No change to formulation or materials
) No change to data reduction software
No change to test parameters A
No change to calibration 人
No change to quality controls

Following is a description of the similarities and differences between the currently marketed HemosIL D-Dimer HS 500 (K090264) and HemosIL D-Dimer HS 500 with the insert sheet modifications:

Similarities
Item	Predicate (K090264)	Modified Device
Indications for Use	HemosIL D-Dimer HS 500 is an automated latexenhanced immunoassay for the quantitativedetermination of D-Dimer in human citratedplasma on the ACL TOP® Family and ACL TOPFamily 50 Series Systems for use, in conjunctionwith a clinical pretest probability (PTP)assessment model to exclude venousthromboembolism (VTE) in outpatientssuspected of deep venous thrombosis (DVT) andpulmonary embolism (PE).For in vitro diagnostic use	Same
Analyte	D-Dimer	Same
Methodology	Latex-enhanced immunoturbidimetric assay	Same
Analyzers	ACL TOP Family and ACL TOP Family 50 Series	Same
Sample Type	Citrated Plasma	Same
Cut-off	500 ng/mL	Same
Linearity	215 - 128000 ng/mL	Same
Detection Limit	203 ng/mL	Same
Performance Claims	No change to labeled performance claims

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Comparison to Predicate (Cont.):

Differences
Item	Predicate (K090264)	Modified Device
Insert Sheet	Current insert language	Insert revisions in italic
Summary and Principle(Insert Section)	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 duringnormal pregnancy but very highlevels are associated withcomplications.	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 normal pregnancy butvery high levels are associated withcomplications.Further, age-adjusted cut-offvalues for DVT and PE suspicionhave been shown to increasespecificity ofD-Dimer and reduce the number ofunnecessary imaging studies inpatient populations greater than50 years.NOTE: Bibliography in insertupdated with applicablesupporting references.
Limitations/InterferingSubstances(Insert Section)	Specimens from patients whohave received preparation ofmouse monoclonal antibody fordiagnosis or therapy maycontain human anti-mouseantibody (HAMA). The presenceof HAMA may cause an over-estimation of results inimmunoassays that utilizemouse monoclonal antibodies.The Reaction Buffer contains ablocking agent against HAMA tominimize this interference onthe assay results.	Specimens from patients who havereceived preparation of mousemonoclonal antibody for diagnosisor therapy may contain humananti-mouse antibody (HAMA). Thepresence of HAMA may cause anover-estimation of results inimmunoassays that utilize mousemonoclonal antibodies. TheReaction Buffer contains a blockingagent against HAMA to minimizethis interference on the assayresults.The performance of this assay hasnot been validated for use withage-adjusted cut-off values.

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Conclusion:

HemosIL D-Dimer HS 500, with the modified Summary and Principle and Limitations/Interfering Substances insert sections, is substantially equivalent to the legally marketed predicate device FDA cleared under K090264.

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).