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 text describes a Special 510(k) submission for the HemosIL von Willebrand Factor Antigen assay. This submission focuses on a modification to the reagent's open vial stability claim, reducing it from 3 months to 14 days, rather than introducing a new AI/ML device or significant performance changes. Therefore, many of the requested categories related to AI/ML device performance, ground truth, and expert evaluation are not directly applicable.

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

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

Performance Characteristic	Acceptance Criteria	Reported Device Performance
Reagent Open Vial Stability	Not explicitly stated in terms of quantitative metric, but the change implies that the reagent must maintain its performance within acceptable limits for 14 days.	The study supported the claim that opened reagents are stable for 14 days at 2-8°C in the original vial.

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

Sample Size: Not specified in the provided text. The text only mentions "testing."
Data Provenance: Not specified in the provided text.
Retrospective or Prospective: Not specified.

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)

Not applicable. This submission concerns a chemical reagent's stability, not an AI/ML device requiring expert ground truth for interpretation. The "ground truth" here is the chemical performance of the reagent over time.

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

Not applicable. Adjudication methods are relevant for subjective interpretations, typically in diagnostic imaging or similar fields. This study assesses objective chemical stability.

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 not an AI/ML device or a diagnostic interpretation study involving human readers.

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

Not applicable. This is not an AI/ML diagnostic algorithm. The study assesses the standalone performance of the reagent's stability.

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

The "ground truth" for this study is the measured performance characteristics of the HemosIL von Willebrand Factor Antigen reagent (e.g., accuracy, precision, linearity) after being opened and stored for various durations up to 14 days, compared to its performance when fresh or within its original 3-month stability claim. The study aims to demonstrate that the reagent's performance remains acceptable throughout the 14-day open-vial period.

8. The sample size for the training set

Not applicable. There is no "training set" as this is not an AI/ML model being developed. The study is a stability test.

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

Not applicable. Refer to point 8.

Summary of the Study:

The study described is an open vial stability study for the HemosIL von Willebrand Factor Antigen reagent. The purpose was to provide data to support a change in the labeled open vial stability claim from 3 months to 14 days.

Study Design: The study was likely a prospective laboratory study where the reagent was opened, stored at 2-8°C, and then tested at various time points (e.g., day 0, day 7, day 14) to assess its performance.
Methodology: The testing was performed in accordance with the established CLSI EP25-A guideline, which provides guidance for evaluating reagent stability. This guideline would specify how to conduct the study, what performance parameters to measure (e.g., accuracy, precision, linearity), and acceptance criteria.
Acceptance Criteria for the Study: While not explicitly listed in quantitative terms, the acceptance criteria would dictate the permissible deviation in performance (e.g., % bias, % CV) of the open and stored reagent compared to a freshly opened reagent or a reference measurement, over the 14-day period. The text states "Testing verified all acceptance criteria were met," implying these criteria were predefined and successfully achieved.
Conclusion: The study demonstrated that the reagent maintained its defined performance specifications for 14 days after opening when stored at 2-8°C, thus supporting the modified insert claim.

Summary

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December 9, 2022

Instrumentation Laboratory Co. Nikita Malladi Regulatory Affairs Manager I 180 Hartwell Road Bedford, Massachusetts 01730

Re: K223402

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: November 8, 2022 Received: November 9, 2022

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,

Takeesha Taylor-bell -S

Deputy Director 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) K223402

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)
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 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.

Submission Type	Special 510(k)
Submitter's Information	Instrumentation Laboratory Company180 Hartwell RoadBedford, MA 01730-2443 (USA)
Contact Person	Nikita MalladiRegulatory Affairs Manager IPhone: 781-674-3245Fax: 781-861-4207Email: nmalladi@werfen.com

Preparation Date	November 08, 2022
Device Trade Name	HemosIL von Willebrand Factor Antigen
Predicate Deviceand 510(k) Number	HemosIL von Willebrand Factor Antigen	K200033

Regulatory Information	Regulation Section No.	21 CFR 864.7290
	Regulation Description	Factor Deficiency Test
	Classification	Class II
	Product Code	GGP
	Classification Panel	Hematology (81)

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Device Description

Indications for Use / Intended Use

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

Reason Submission Qualifies as Special 510(k)

This Special 510(k) is being submitted to modify the open vial stability labeled claim for HemosIL von Willebrand Factor Antigen from 3 months to 14 days based on testing to the current CLSI EP25-A guideline.

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

. The proposed change is 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 change in this submission does not introduce:

Changes to indications for use or intended use .
. Changes to operating principle
Changes to formulation .
Changes to labeled performance claims, except to reduce the open vial stability claim to 14 days ●
Changes to assay algorithms or data reduction software ●

Design Control Activities

The open vial stability study was performed in accordance to an established plan and protocol and design control procedures. Testing verified all acceptance criteria were met.

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Comparison to Predicate Device
Similarities
Item	Predicate (K200033)	Subject Device
Trade Name	HemosIL von Willebrand Factor Antigen	Same
Manufacturer	Instrumentation Laboratory Company	Same
Intended Use/Indications for Use	Automated latex enhanced immunoassay forthe 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 plasma containingVWF:Ag is mixed with the Latex Reagent andthe Reaction Buffer included in the kit, thecoated latex particles agglutinate. The degreeof agglutination is directly proportional to theconcentration of VWF:Ag in the sample and isdetermined by measuring the decrease oftransmitted light 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
Instrumentation	ACL Elite / ACL Elite Pro K060162ACL TOP Family K160276ACL TOP Family 50 Series K150877	Same
Comparison to Predicate Device (Cont.)
Differences
Item	Predicate (K200033)	Subject Device
Reagent Open VialStability	Current Insert ClaimOpened reagents are stable 3 months at2-8°C in the original vial.	Modified Insert ClaimOpened reagents are stable 14 days at2-8°C in the original vial.

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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).