HemosIL Factor XII Deficient Plasma by Instrumentation Laboratory Co.

HemosIL Factor XII Deficient Plasma immunodepleted of factor XII and intended for the in vitro diagnostic quantitative determination of factor XII activity in citrated plasma, based on the activated partial thromboplastin time (APTT) assay, on IL Coagulation Systems.

Device Description

Factor XII activity in a patient's plasma is determined by performing a modified activated partial thromboplastin time test (APTT). Patient plasma is diluted and added to plasma deficient in factor XII. Correction of the clotting time of the deficient plasma is proportional to the concentration (% activity) of that factor in the patient plasma, interpolated from a calibration curve.

AI/ML Overview

The provided text describes a 510(k) submission for a medical device called "HemosIL Factor XII Deficient Plasma." This submission is a "Special 510(k)" because the changes are limited to an updated on-board instrument stability claim, which means only specific performance characteristics related to this change were tested.

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

Key Takeaway from the Document: This is not a study proving the overall efficacy or safety of a new diagnostic algorithm or AI system. Instead, it's a regulatory submission for a minor modification to an existing reagent used in a diagnostic test. The study described focuses solely on validating a change in the reagent's "on-board instrument stability" claim, meaning how long the reagent is stable once placed on the testing instrument. Therefore, many of the typical acceptance criteria and study aspects found in AI/algorithm submissions (like MRMC studies, expert consensus on images, etc.) are not applicable here.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by standard laboratory validation practices for a changed stability claim, specifically referencing CLSI EP25-A. The performance is the outcome of this validation.

Acceptance Criterion (Implied)	Reported Device Performance
Validation of "on-board instrument stability" claim	New claim of 6 Hours for on-board stability on ACL TOP Family and ACL TOP Family 50 Series coagulation systems. (Previously 24 Hours)
Compliance with CLSI EP25-A requirements for validation of stability	Testing was conducted "under design control and in accordance with CLSI EP25-A."
Continued equivalence to predicate device in other performance characteristics	Stated: "HemosIL Factor XII Deficient Plasma ... share the same Intended Use/ Indications for Use, same test principle, same formulation and the same performance characteristics, except for the updated on-board instrument claim."

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

Sample Size: The document does not explicitly state the sample size (number of patient samples, runs, or measurements) used for the stability testing. It only mentions "additional testing done to current CLSI EP25-A requirements" and that "verification testing to establish the modified on-board instrument stability claim... was conducted under design control."
Data Provenance: The document does not specify the country of origin of the data or whether the testing was retrospective or prospective. It implies the testing was conducted by Instrumentation Laboratory Co. as part of their design control process. Given it's a stability study for a reagent, it would inherently be a prospective study conducted in a laboratory setting.

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

Not Applicable. This is not a study involving expert readers interpreting medical images or data where "ground truth" is established by human consensus. The "ground truth" for a reagent's stability is determined by laboratory measurements and adherence to pre-defined acceptance limits for analytical performance (e.g., maintaining accuracy, precision within a certain range over time).

4. Adjudication Method for the Test Set

Not Applicable. As this is a laboratory stability study for a reagent, there is no "adjudication" of human interpretations involved. The "adjudication" would be based on objective analytical measurements compared against pre-defined statistical criteria (e.g., drift, bias within acceptable limits according to CLSI EP25-A).

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No. An MRMC study is relevant for evaluating human performance (e.g., diagnostic accuracy of radiologists) with and without AI assistance. This submission is for a reagent, not an AI system or diagnostic algorithm that interacts with human readers.

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

No. This is not an algorithm or AI system. It's a laboratory reagent. The "performance" being evaluated is the chemical stability of the reagent on an automated instrument.

7. The Type of Ground Truth Used

Analytical Performance Data / Reference Method. The "ground truth" for reagent stability in this context would be defined by the reagent's ability to produce accurate and precise results when tested immediately after reconstitution (time zero) and then over the claimed stability period (e.g., 6 hours). This would be compared against a reliable reference method or pre-established acceptable analytical performance ranges. The CLSI EP25-A guideline would specify how this analytical "ground truth" is established and evaluated.

8. The Sample Size for the Training Set

Not Applicable. There is no "training set" as this is not a machine learning model or AI algorithm. This is a chemical reagent.

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

Not Applicable. As there is no training set, this question is not relevant.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" in a square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION".

March 22, 2018

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

Re: K180486

Trade/Device Name: HemosIL Factor XII Deficient Plasma Regulation Number: 21 CFR 864.7290 Regulation Name: Factor deficiency test Regulatory Class: Class II Product Code: GJT Dated: February 22, 2018 Received: February 23, 2018

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. 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 Part 801 and Part 809); medical device 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

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Part 820); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

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) K180486

Device Name HemosIL Factor XII Deficient Plasma

Indications for Use (Describe)

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 is being submitted in accordance with the requirements of 21 CER 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	Carol Marble, Regulatory Affairs DirectorPhone: 781-861-4467Fax: 781-861-4207Email: cmarble@ilww.com
Preparation Date	February 22, 2018
Device Trade Name	HemosIL Factor XII Deficient Plasma
Regulatory Information	Regulation Number	21 CFR 864.7290
	Regulation Description	Factor Deficiency Test
	Classification	Class II
	Product Code	GJT
	Classification Panel	Hematology (81)
Predicate Device	K043459	HemosIL Factor XII Deficient Plasma
Device Description	Factor XII activity in a patient's plasma is determined by performinga modified activated partial thromboplastin time test (APTT).Patient plasma is diluted and added to plasma deficient in factor XII.Correction of the clotting time of the deficient plasma isproportional to the concentration (% activity) of that factor in thepatient plasma, interpolated from a calibration curve.
Intended Use	Human plasma immunodepleted of factor XII for the quantitative determination of factor XII (FXII) activity in citrated plasma, based on activated partial thromboplastin time (APTT) assay, on IL Coagulation Systems.

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Indications for Use	HemosIL Factor XII Deficient Plasma is human plasmaimmunodepleted of factor XII and intended for the in vitrodiagnostic quantitative determination of factor XII activity incitrated plasma, based on the activated partial thromboplastintime (APTT) assay, on IL Coagulation Systems.
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Description of the Modification	The on-board instrument claim in the HemosIL Factor XII DeficientPlasma insert sheet is being updated as follows based on additionaltesting done to current CLSI EP25-A requirements.
	Current Claim: 24 Hours	Modified Claim: 6 Hours

Reason SubmissionQualifies as Special 510(k)	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 performance claims, except for the on-board stability
	• 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 calibration
	• No change to quality controls

Design Control Activities	The verification testing to establish the modified on-boardinstrument stability claim for HemosIL Factor XII Deficient Plasmawas conducted under design control and in accordance with CLSIEP25-A.
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Comparison to Predicate
Similarities
Item	Predicate (K043459)	Modified Device
Intended Use	Human plasma immunodepleted of factor XIIfor the quantitative determination of factor XII(FXII) activity in citrated plasma, based onactivated partial thromboplastin time (APTT)assay, on IL Coagulation Systems.	Same
Indications for Use	HemosIL Factor XII Deficient Plasma is humanplasma immunodepleted of factor XII andintended for the in vitro diagnosticquantitative determination of factor XIIactivity in citrated plasma, based on theactivated partial thromboplastin time (APTT)assay, on IL Coagulation Systems.	Same
Measurand	Factor XII Activity	Same
Type of Test	Functional Clotting Assay	Same
Methodology	Abnormalities of the intrinsic pathway factorsare determined by performing a modifiedactivated partial thromboplastin time (APTT)test. Patient plasma is diluted and added toplasma deficient in factor XII. Correction of theclotting time of the deficient plasma isproportional to the concentration (% activity)of factor XII in the patient plasma,interpolated from a calibration curve.	Same
Sample Type	Citrated Plasma	Same
On-Board InstrumentStability withFollowing Analyzers	ACL TOP Family:ACL TOP 300 CTS ACL TOP 500 CTS ACL TOP 700 ACL TOP 700 CTS ACL TOP 700 LAS ACL TOP Family 50 Series: ACL TOP 350 CTS ACL TOP 550 CTS ACL TOP 750 ACL TOP 750 CTS ACL TOP 750 LAS	Same
Expected Value Range	50-150% (0.50-1.50 IU/mL)	Same
Differences
On-Board Claim	24 Hours	6 Hours

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Conclusion	HemosIL Factor XII Deficient Plasma and the currently marketed deficientplasma share the same Intended Use/ Indications for Use, same testprinciple, same formulation and the same performance characteristics,except for the updated on-board instrument claim for the ACL TOP Familyand ACL TOP Family 50 Series.
	Therefore, HemosIL Factor XII Deficient Plasma with an updated on-boardinstrument claim is substantially equivalent to the currently marketedpredicate device that is FDA cleared under K043459.

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).