HemosIL Liquid Anti-Xa is an automated chromogenic assay for in vitro diagnostic use by laboratory professionals in clinical laboratories. The assay provides quantitative results on 3.2% citrated human plasma for the following analytes based on the calibrators used:

· When used with HemosIL Heparin Calibrators: Quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity on the ACL TOP Family and ACL TOP Family 50 Series.
· When used with HemosIL Apixaban Calibrators:

Quantitative determination of apixaban on the ACL TOP Family 50 Series through measurement of Factor Xa activity, which is inversely proportional to the apixaban level. With HemosIL Apixaban Calibrators, the assay is intended to measure apixaban concentrations in patients on apixaban therapy in the following situations where measurement of apixaban levels could be useful to have as additional information:

Patients at risk for major bleeding
Patients experiencing a bleeding episode

The assay is not a stand-alone test and the results should be used in conjunction with other clinical and laboratory findings.

For use in adult population. For prescription use only.

Device Description

HemosIL Liquid Anti-Xa is a one stage chromogenic assay based on a synthetic chromogenic substrate and on Factor Xa inactivation. The assay provides quantitative results on 3.2% citrated human plasma for the following analytes based on the calibrators used:

. When used with HemosIL Heparin Calibrators:

Heparin levels in patient plasma are measured automatically on ACL TOP Family and ACL TOP Family 50 Series when this assay is calibrated with HemosIL Heparin Calibrators.

Heparin is analyzed as a complex with antithrombin present in the sample. The concentration of this complex is dependent on the availability of the patient's endogenous antithrombin. When the heparinantithrombin complex is formed, two competing reactions take place.

1. Factor Xa is neutralized by heparin-antithrombin complex.
1. Residual Factor Xa is quantified with a synthetic chromogenic substrate. The paranitroaniline released is monitored kinetically at 405 nm and is inversely proportional to the heparin level in the sample.

In order to reduce the influence from heparin antagonists, such as platelet factor 4 (PF4), dextran sulfate is included in the reaction mixture.

When used with HemosIL Apixaban Calibrators: .

Apixaban levels in patient plasma are measured automatically on ACL TOP Family and ACL TOP Family 50 Series when this assay is calibrated with HemosIL Apixaban Calibrators.

Apixaban directly inhibits Factor Xa activity independent of the antithrombin present. The Factor Xa activity measured by the assay is exogenous. Factor Xa is neutralized directly by apixaban.

Residual Factor Xa is quantified with a synthetic chromogenic substrate. The paranitroaniline released is monitored kinetically at 405 nm and is inversely proportional to the apixaban level in the sample.

Measurement of apixaban concentration is recommended by the International Society of Thrombosis and Hemostasis Subcommittee on Control of Anticoagulation in certain clinical scenarios including bleeding episodes, perioperative management, and suspicion of overdose.

AI/ML Overview

The provided document is a 510(k) summary for a medical device (HemosIL Liquid Anti-Xa), primarily focused on a specific change: modifying the labeled on-board instrument stability claim from 7 days to 4 days and removing claims for a particular instrument family (ACL Elite/Elite Pro). This type of submission (Special 510(k)) indicates that the core device and its fundamental performance characteristics are already established and the submission is for a minor modification.

Therefore, the document does not contain the information typically found in a clinical study report that would establish the initial acceptance criteria and prove the device meets them from scratch. It refers to a guideline (CLSI EP25-A) for the testing conducted for the stability claim change, but doesn't detail the acceptance criteria for the entire device's performance (e.g., accuracy, precision, linearity, etc., across its full analytical range).

The information requested in the prompt (sample size for test set, data provenance, number/qualifications of experts, adjudication method, MRMC study, standalone performance, ground truth establishment for training and test sets) is characteristic of studies for diagnostic devices, particularly AI/software-as-a-medical-device (SaMD) products, where performance is often evaluated against human expert consensus or clinical outcomes. The HemosIL Liquid Anti-Xa is an in vitro diagnostic (IVD) assay, not an AI/SaMD product that requires human expert review of images or signals for ground truth. Its performance validation relies on analytical studies (e.g., accuracy against reference methods, precision, linearity, interference studies).

Based on the provided document, I cannot fulfill most of the requested information because it is not contained within this 510(k) summary.

Specifically, the document:

Does not provide a full table of acceptance criteria for the device's overall performance (only discusses a change in stability claim).
Does not discuss aspects like sample size for test sets in the context of clinical performance evaluation against a human-established ground truth, data provenance for such sets, expert numbers/qualifications, or adjudication methods, as these are typically not relevant for an IVD reagent's analytical performance assessment in the same way they are for image-based AI diagnostics.
Does not mention any multi-reader multi-case (MRMC) comparative effectiveness study, as it's not an AI-assisted diagnostic tool.
Does not discuss standalone algorithm performance, as it's a reagent for an automated instrument.
Does not specify the type of ground truth used in the context of human expert review. For an IVD, "ground truth" would typically refer to reference method results or clinical diagnosis established through established laboratory and clinical procedures.
Does not provide information on training set sample size or how ground truth was established for a training set, as it is not an AI/machine learning device that undergoes a training phase in the typical sense.

The only relevant information that can be extracted regarding a "study" is for the change being submitted:

1. Acceptance Criteria and Device Performance (for On-Board Stability Change):

The document states the study was conducted "based on testing to the current CLSI EP25-A guideline" to support the change in on-board stability from 7 days to 4 days. While it doesn't explicitly list the numerical acceptance criteria for this specific study, the implication is that the data collected over 4 days met the performance specifications (e.g., accuracy, precision) as defined by the CLSI EP25-A guideline for reagent stability. The reported performance is that the device meets the 4-day stability claim, leading to the regulatory approval.

Acceptance Criteria (Implied by CLSI EP25-A for Stability)	Reported Device Performance (within 4 days)
Performance (e.g., accuracy, precision) within specifications for the stated analyte range.	Met for 4 days at 15-25°C

2. Sample Size and Data Provenance for Stability Test: While the specific sample size for the stability study is not detailed, it would involve multiple replicates of control and/or patient samples measured over the 4-day period on the specified instruments (ACL TOP Family and ACL TOP Family 50 Series) stored at 15-25°C. Data provenance would be from internal laboratory studies of Instrumentation Laboratory Co. (the manufacturer). This would be a prospective analytical study designed to assess reagent stability under defined conditions.

3. Number of Experts and Qualifications / Adjudication Method / MRMC Study / Standalone Performance: Not applicable for this type of IVD reagent validation. There are no human experts involved in establishing ground truth for analytical performance, nor is there a multi-reader study or standalone algorithm.

4. Type of Ground Truth Used: For analytical performance like stability, the "ground truth" would be the initial performance of the freshly prepared reagent or its performance compared to a reference method, against which subsequent measurements over time are compared to assess degradation. This is an analytical ground truth, not a clinical ground truth established by human experts.

5. Training Set Sample Size and Ground Truth Establishment: Not applicable. This is an IVD reagent and not an AI/ML device that requires a "training set" in the sense of machine learning. The design and parameters of the assay are established through chemical and biological research and development, not data-driven machine learning.

Summary

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October 4, 2022

Instrumentation Laboratory Co. Carol Marble Sr. Regulatory Affairs Director 180 Hartwell Road Bedford, Massachusetts 01730

Re: K213464

Trade/Device Name: HemosIL Liquid Anti-Xa Regulation Number: 21 CFR 864.7525 Regulation Name: Heparin Assay Regulatory Class: Class II Product Code: KFF, QLU Dated: June 3, 2022 Received: June 6, 2022

Dear Carol 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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Min Wu Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

Device Name HemosIL Liquid Anti-Xa

Indications for Use (Describe)

· When used with HemosIL Heparin Calibrators: Quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity on the ACL TOP Family and ACL TOP Family 50 Series.
· When used with HemosIL Apixaban Calibrators:

Patients at risk for major bleeding
Patients experiencing a bleeding episode

The assay is not a stand-alone test and the results should be used in conjunction with other clinical and laboratory findings.

For use in adult population. For prescription use only.

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

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

Submitter's Information	Instrumentation Laboratory Company180 Hartwell RoadBedford, MA 01730-2443 (USA)
-------------------------	-----------------------------------------------------------------------------------------

Contact Person	Carol MarbleSenior Director of Quality Assurance and Regulatory Affairs
	Phone: 781-861-4467
	Fax: 781-861-4207
	Email: cmarble@werfen.com

Preparation Date	June, 2022
------------------	------------

Device Trade Name	HemosIL Liquid Anti-Xa
-------------------	------------------------

Predicate Device	HemosIL Liquid Anti-Xa	K090209, DEN190032
------------------	------------------------	--------------------

Regulatory Information
Analyte	RegulationSection	Regulatory Description	Class	ProductCode	Panel
Heparin	864.7525	Heparin Assay	II	KFF	81
Apixaban	864.7295	Anti-factor Xa Activity Test System, Apixaban	II	QLU

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Device Description

. When used with HemosIL Heparin Calibrators:

Heparin levels in patient plasma are measured automatically on ACL TOP Family and ACL TOP Family 50 Series when this assay is calibrated with HemosIL Heparin Calibrators.

1. Factor Xa is neutralized by heparin-antithrombin complex.
1. Residual Factor Xa is quantified with a synthetic chromogenic substrate. The paranitroaniline released is monitored kinetically at 405 nm and is inversely proportional to the heparin level in the sample.

In order to reduce the influence from heparin antagonists, such as platelet factor 4 (PF4), dextran sulfate is included in the reaction mixture.

When used with HemosIL Apixaban Calibrators: .

Apixaban levels in patient plasma are measured automatically on ACL TOP Family and ACL TOP Family 50 Series when this assay is calibrated with HemosIL Apixaban Calibrators.

Apixaban directly inhibits Factor Xa activity independent of the antithrombin present. The Factor Xa activity measured by the assay is exogenous. Factor Xa is neutralized directly by apixaban.

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Indications for Use / Intended Use

When used with HemosIL Heparin Calibrators: .

Quantitative determination of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) activity on the ACL TOP Family and ACL TOP Family 50 Series.

. When used with HemosIL Apixaban Calibrators:

Quantitative determination of apixaban on the ACL TOP Family and ACL TOP Family 50 Series through measurement of Factor Xa activity, which is inversely proportional to the apixaban level. With HemosIL Apixaban Calibrators, the assay is intended to measure apixaban concentrations in patients on apixaban therapy in the following situations where measurement of apixaban levels could be useful to have as additional information:

-Patients at risk for major bleeding
-Patients experiencing a bleeding episode

The assay is not a stand-alone test and the results should be used in conjunction with other clinical and laboratory findings.

For use in adult population. For prescription use only.

Reason for Submission

This Special 510(k) is being submitted to modify the labeled on-board instrument stability claims for HemosIL Liquid Anti-Xa on the ACL TOP Family and ACL TOP Family 50 Series from 7 days to 4 days for heparin and apixaban based on testing to the current CLSI EP25-A guideline. This submission also removes claims for heparin measurement on the ACL Elite/Elite Pro instrument family from the HemosIL Liquid Anti-Xa labeling.

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

The proposed changes are submitted by the manufacturer legally authorized to market the existing . device.
There is a well-established method to evaluate the change: CLSI EP25-A.
The data can be reviewed in a summary or risk analysis format. ●

In addition, the changes in this submission do not introduce:

. Changes to indications for use or intended use, except to remove the ACL Elite/Elite Pro instrument family
Changes to operating principle ●
Changes to formulation ●
Changes to labeled performance claims, except to reduce the on-board instrument stability claims for ● the ACL TOP Family/ACL TOP Family 50 Series to 4 days for heparin and apixaban and to remove all claims for heparin measurement with the ACL Elite/Elite Pro instrument family

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Comparison to Predicate
Item	Predicate Device[K090209 (heparin), DEN190032 (apixaban)]	Subject Device
Similarities
Trade Name	HemosIL Liquid Anti-Xa	Same
Manufacturer	Instrumentation Laboratory Company	Same
Intended Use/Indications forUse(Changes in BlueandStrikethrough)	HemosIL Liquid Anti-Xa is an automated chromogenic assay forin vitro diagnostic use by laboratory professionals in clinicallaboratories. The assay provides quantitative results on 3.2%citrated human plasma for the following analytes based on thecalibrators used:When used with HemosIL Heparin Calibrators:Quantitative determination of unfractionated heparin (UFH)and low molecular weight heparin (LMWH) activity on theACL TOP Family, and ACL TOP Family 50 Series, andACL Elite/Elite Pro. When used with HemosIL Apixaban Calibrators:Quantitative determination of apixaban on the ACL TOPFamily and ACL TOP Family 50 Series throughmeasurement of Factor Xa activity, which is inverselyproportional to the apixaban level. With HemosIL ApixabanCalibrators, the assay is intended to measure apixabanconcentrations in patients on apixaban therapy in thefollowing situations where measurement of apixaban levelscould be useful to have as additional information:- Patients at risk for major bleeding- Patients experiencing a bleeding episode The assay is not a stand-alone test and the results should be usedin conjunction with other clinical and laboratory findings.For use in adult population. For prescription use only.	Same, exceptfor removal ofACL Elite/ElitePro instrumentfamily
Comparison to Predicate
Item	Predicate Device[K090209 (heparin), DEN190032 (apixaban)]	Subject Device
Similarities (Cont.)
Test Principle	One stage chromogenic assay based on a syntheticchromogenic substrate and on factor Xa inactivation	Same
Sample Type	3.2% Citrated Plasma	Same
Measurement	Quantitative	Same
Reporting Units	HeparinIU/mL	Same
	Apixabanng/mL
Quality Control	Automated QC	Same
Limit of Detection	Heparin0.04 IU/mL	Same
	Apixaban9 ng/mL
Linearity	HeparinUp to 2 IU/mL	Same
	Apixaban20 ng/mL – 1000 ng/mL

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Item	Predicate Device[K090209 (heparin),DEN190032 (apixaban)]	Subject Device
Differences
Instrumentation	ACL TOP Family (K160276)ACL TOP Family 50 Series (K150877)ACL Elite/Elite Pro (K060162)	ACL TOP Family (K160276)ACL TOP Family 50 Series (K150877)Note: ACL Elite/Elite Pro claims removed
On-BoardStability	7 days at 15-25°C on the ACL TOPFamily/ACL TOP Family 50 Series forheparin and apixaban	4 days at 15-25°C on the ACL TOPFamily/ACL TOP Family 50 Series forheparin and apixaban

Regulation Number and Section

§ 864.7525 Heparin assay.

(a)
Identification. A heparin assay is a device used to determine the level of the anticoagulant heparin in the patient's circulation. These assays are quantitative clotting time procedures using the effect of heparin on activated coagulation factor X (Stuart factor) or procedures based on the neutralization of heparin by protamine sulfate (a protein that neutralizes heparin).(b)
Classification. Class II (performance standards).