HemosIL von Willebrand Factor Antigen by Instrumentation Laboratory Co.

Automated latex enhanced immunoassay for the quantitative determination of von Willebrand Factor Antigen (VWF:Ag) in human citrated plasma on IL Coagulation Systems.

Device Description

The VWF:Ag kit is a latex particle enhanced immunoturbidimetric assay to quantify VWF:Ag in plasma. When a plasma containing VWF:Ag is mixed with the Latex Reagent and the Reaction Buffer included in the kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of VWF:Ag in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.

AI/ML Overview

The provided document is a 510(k) Summary for the HemosIL von Willebrand Factor Antigen device. It describes a Special 510(k) submission rather than a traditional premarket notification that would typically include substantial new performance data. The core of this submission is a modification to a limitation/interference claim regarding Rheumatoid Factor (RF) rather than a broader study proving overall device performance against new acceptance criteria.

Therefore, the requested information, particularly regarding a comprehensive study with a test set, expert adjudication, MRMC studies, and standalone performance for an AI/algorithm-based device, is not present in this document. This submission pertains to an in-vitro diagnostic (IVD) assay that measures a biological marker, not an AI-powered diagnostic device.

However, I can extract the relevant information from the document regarding the acceptance criteria related to the modified claim and the "study" (which in this context refers to the basis for the change, here being a literature reference and internal design control activities rather than a new clinical trial).

Here's an attempt to answer based on the provided document, while clarifying what information is missing due to the nature of this particular 510(k) submission:

Acceptance Criteria and Device Performance for HemosIL von Willebrand Factor Antigen (K200033) - Modifed Rheumatoid Factor Interference Claim

This 510(k) submission is a Special 510(k), indicating a minor change to an already cleared device. The "acceptance criteria" and "study" are specifically focused on the modified claim regarding Rheumatoid Factor interference, rather than a broad re-evaluation of the device's overall performance. No new clinical study was conducted for this specific submission to prove general device performance. Instead, the modification is based on internal design control activities and a literature reference.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criterion for this specific modification is the non-interference within a certain concentration range of Rheumatoid Factor (RF). The "reported device performance" reflects a change in the claimed non-interference level.

Acceptance Criterion (for RF interference)	Reported Device Performance (Modified Claim)
Previous Claim:	New Claim:
VWF:Ag results on ACL Family Systems not affected by RF up to 750 IU/mL. (Note: Original document states "may produce an overestimation" for ACL Family, but for ACL TOP it says "not affected up to 750 IU/mL").	VWF:Ag results on ACL Family Systems are not affected by Rheumatoid Factor up to 50 IU/mL.
VWF:Ag results on ACL TOP Family and ACL TOP Family 50 Series not affected by RF up to 750 IU/mL.	VWF:Ag results on ACL TOP Family and ACL TOP Family 50 Series are not affected by Rheumatoid Factor up to 50 IU/mL.
Interpretation: The new claim reduces the stated non-interference level for RF on all listed systems to 50 IU/mL. This implies that the previous claim of 750 IU/mL for ACL TOP systems was either incorrect or no longer supported, and for ACL Family systems, the previous "overestimation" warning is being replaced with a non-interference claim up to 50 IU/mL.

Note on "Acceptance Criteria" for a Special 510(k): For this type of submission, the primary acceptance criterion is that the modified device remains substantially equivalent to the predicate device and that the change does not introduce new questions of safety or effectiveness. For the specific change (RF interference), the acceptance is based on the rationale provided (literature reference). No specific quantitative performance metric (e.g., accuracy, sensitivity, specificity) for the RF non-interference claim is explicitly stated, other than the new 50 IU/mL threshold being deemed acceptable.

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

Test Set Sample Size: Not applicable. The document explicitly states: "Performance data are unnecessary since the current Rheumatoid Factor claim in the HemosIL von Willebrand Factor Antigen insert is being replaced with a limitation and a supporting literature reference." This indicates that a dedicated new test set for this specific change was not used for performance validation.
Data Provenance: Not explicitly stated as new data was not generated. The basis for the change is a "supporting literature reference."

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

Not applicable. There was no new test set requiring expert ground truth establishment for this specific change.

4. Adjudication Method for the Test Set

Not applicable. No new test set requiring adjudication was used.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not applicable. This device is an in-vitro diagnostic assay, not an AI-assisted diagnostic tool that would typically involve human readers.

6. Standalone Performance Study (Algorithm Only)

Not applicable. This device is an in-vitro diagnostic assay. The concept of "standalone performance" typically applies to AI algorithms operating independently of human interpretation.

7. Type of Ground Truth Used

For the modified RF interference claim: The "ground truth" for the new claim (non-interference up to 50 IU/mL) is based on a "supporting literature reference" combined with internal design control activities and possibly previous knowledge/studies that led to the revised understanding of RF interference. No new direct "ground truth" (e.g., from pathology, clinical outcomes, or expert consensus on new data) was established for this specific special 510(k).

8. Sample Size for the Training Set

Not applicable. This is an IVD assay, not an AI/machine learning algorithm that requires a training set.

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

Not applicable. No training set was used.

Summary of Key Takeaway from the Document:

This 510(k) submission (K200033) is a Special 510(k) for the HemosIL von Willebrand Factor Antigen. The purpose is to modify the product insert's "Limitations/Interfering substances" section concerning Rheumatoid Factor interference. The submission states that no new performance data was generated or deemed necessary for this change because it relies on existing knowledge and a literature reference. Therefore, the detailed requirements for a study proving device performance (especially for an AI/algorithm) are not met by this particular regulatory filing, as it pertains to a different type of device and a very specific, limited modification.

Summary

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August 19, 2020

Instrumentation Laboratory Co. Nikita Malladi Principal Regulatory Affairs Specialist 180 Hartwell Road Bedford, Massachusetts 01730

Re: K200033

Trade/Device Name: HemosIL von Willebrand Factor Antigen Regulation Number: 21 CFR 864.7290 Regulation Name: Factor deficiency test Regulatory Class: Class II Product Code: GGP Dated: July 17, 2020 Received: July 20, 2020

Dear Nikita 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. 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,

for Takeesha Taylor-Bell Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health 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) K200033

Device Name

HemosIL von Willebrand Factor Antigen

Indications for Use (Describe)

Automated latex enhanced immunoassay for the quantitative determination of von Willebrand Factor Antigen (VWF:Ag) in human citrated plasma on IL Coagulation Systems.

Type of Use (Select one or both, as applicable)
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X | 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 is being submitted in accordance with the requirements of 21 CFR 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	Nikita Malladi, Principal Regulatory Affairs Specialist
	Phone: 781-674-3245
	Fax: 781-861-4207
	Email: nmalladi@ilww.com

Preparation Date	August 4, 2020
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Device Trade Name	HemosIL von Willebrand Factor Antigen
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	Regulation Number	21 CFR 864.7290
	Regulation Description	Factor Deficiency Test
Regulatory Information	Classification	Class II
	Product Code	GGP
	Classification Panel	Hematology (81)

Predicate Device	K992704	HemosIL von Willebrand FactorAntigen
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Device Description	The VWF:Ag kit is a latex particle enhanced immunoturbidimetricassay to quantify VWF:Ag in plasma. When a plasma containingVWF:Ag is mixed with the Latex Reagent and the Reaction Bufferincluded in the kit, the coated latex particles agglutinate. Thedegree of agglutination is directly proportional to theconcentration of VWF:Ag in the sample and is determined bymeasuring the decrease of transmitted light caused by theaggregates.
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Device Description

The VWF:Ag kit is a latex particle enhanced immunoturbidimetricassay to quantify VWF:Ag in plasma. When a plasma containingVWF:Ag is mixed with the Latex Reagent and the Reaction Bufferincluded in the kit, the coated latex particles agglutinate. Thedegree of agglutination is directly proportional to theconcentration of VWF:Ag in the sample and is determined bymeasuring the decrease of transmitted light caused by theaggregates.

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Intended Use/Indications for Use	Automated latex enhanced immunoassay for the quantitativedetermination of von Willebrand Factor Antigen (VWF:Ag) inhuman citrated plasma on IL Coagulation Systems.
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	The claim for Rheumatoid Factor in the “Limitations/Interferingsubstances” section of the HemosIL von Willebrand Factor Antigeninsert sheet is being modified as follows:
	Current Insert Claim	Modified Insert Claim
Description of the Modification	The presence of RheumatoidFactor may produce anoverestimation of VWF:Agresults on ACL Family Systems.VWF:Ag results on ACL TOPFamily and ACL TOP Family 50Series are not affected byRheumatoid Factor up to 750IU/mL.	VWF:Ag results on ACL FamilySystems are not affected byRheumatoid Factor up to 50IU/mL.VWF:Ag results on ACL TOPFamily and ACL TOP Family 50Series are not affected byRheumatoid Factor up to 50IU/mL.

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Reason SubmissionQualifies as Special 510(k)	This submission for the Hemosll von Willebrand Factor Antigenmeets the criteria for a Special 510(k) outlined in the FDA guidance"The Special 510(k) Program: Guidance for Industry and Food andDrug Administration Staff" (September 13, 2019) based on thefollowing:
	• The proposed change is submitted by the manufacturer legallyauthorized to market the existing device.
	• Performance data are unnecessary since the currentRheumatoid Factor claim in the HemosIL von WillebrandFactor Antigen insert is being replaced with a limitation and asupporting literature reference.
	In addition, the change described in this submission does notintroduce:
	• Changes to indications for use or intended use
	• Changes to operating principle
	• Changes to assay formulation
	• Changes to analytical performance claims, except toRheumatoid Factor interference claim
	• Changes to assay algorithms or data reduction software

Design Control Activities	The Rheumatoid Factor interference claim in the HemosIL vonWillebrand Factor Antigen insert sheet is being modified to indicatethat VWF:Ag results on ACL Family Systems, ACL TOP Family and ACLTOP Family 50 Series are not affected by Rheumatoid Factor up to	50 IU/mL.
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Comparison to Predicate
Similarities
Item	Predicate (K992704)	Modified Device
Intended Use	Automated latex enhanced immunoassayfor the quantitative determination of vonWillebrand Factor Antigen (VWF:Ag) inhuman citrated plasma on IL CoagulationSystems.	Same
Measurand	von Willebrand Factor Antigen	Same
Type of Test	Latex immunoassay	Same
Methodology	The VWF:Ag kit is a latex particle enhancedimmunoturbidimetric assay to quantifyVWF:Ag in plasma. When a plasmacontaining VWF:Ag is mixed with the LatexReagent and the Reaction Buffer included inthekit, the coated latex particlesagglutinate. The degree of agglutination isdirectly proportional to the concentrationof VWF:Ag in the sample and is determinedby measuring the decrease of transmittedlight caused by the aggregates.	Same
Sample Type	Citrated Plasma	Same
Kit Composition	Latex Reagent: 2 vials x 3 mL of a suspensionof polystyrene latex particles coated with arabbit polyclonal antibody directed againstVWF containing bovine serum albumin,buffer, stabilizer and preservative.Reaction Buffer: 2 vials x 4 mL of HEPESbuffer containing bovine serum albumin,stabilizers and preservative.	Same
Differences
	Current Insert Claim	Modified Insert Claim
Limitations/InterferingSubstances	The presence of Rheumatoid Factormay produce an overestimation ofVWF:Ag results on ACL FamilySystems.VWF:Ag results on ACL TOP Familyand ACL TOP Family 50 Series arenot affected by Rheumatoid Factorup to 750 IU/mL.	VWF:Ag results on ACL FamilySystems are not affected byRheumatoid Factor up to 50 IU/mL.VWF:Ag results on ACL TOP Familyand ACL TOP Family 50 Series are notaffected by Rheumatoid Factor up to50 IU/mL.

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Conclusion	HemosIL von Willebrand Factor Antigen and the currently marketed assayshare the same Intended Use/Indications for Use, same operating principle,same formulation and comparable performance characteristics, except forthe modified claim of no interference from Rheumatoid Factor up to 50IU/mL. Therefore, HemosIL von Willebrand Factor Antigen with a modifiedRheumatoid Factor interference claim is substantially equivalent to thecurrently marketed predicate device FDA cleared under K992704.
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Conclusion

HemosIL von Willebrand Factor Antigen and the currently marketed assayshare the same Intended Use/Indications for Use, same operating principle,same formulation and comparable performance characteristics, except forthe modified claim of no interference from Rheumatoid Factor up to 50IU/mL. Therefore, HemosIL von Willebrand Factor Antigen with a modifiedRheumatoid Factor interference claim is substantially equivalent to thecurrently marketed predicate device FDA cleared under K992704.

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Regulation Number and Section

§ 864.7290 Factor deficiency test.

(a)
Identification. A factor deficiency test is a device used to diagnose specific coagulation defects, to monitor certain types of therapy, to detect coagulation inhibitors, and to detect a carrier state (a person carrying both a recessive gene for a coagulation factor deficiency such as hemophilia and the corresponding normal gene).(b)
Classification. Class II (performance standards).