HemosIL Factor XII Deficient Plasma is human 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 and ELECTRA Systems. Abnormalities of the intrinsic pathway factors are determined by performing a modified activated partial thromboplastin time (APTT) test. Patient plasma is diluted and added to a plasma deficient in factor XII. Correction of the clotting time of the deficient plasma is proportional to the concentration (% activity) of the factor XII in the patient plasma, interpolated from a calibration curve.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the HemosIL Factor XII Deficient Plasma, based on the provided text:

Acceptance Criteria and Reported Device Performance

For this specific device, the acceptance criteria are not explicitly stated as numerical cutoffs. Instead, the study aims to demonstrate substantial equivalence to predicate devices. This means that the new device's performance, as measured by method comparison and precision, should be comparable to the legally marketed predicates.

The summary highlights:

Method Comparison: Consistency in results (slope and correlation coefficients) when compared to predicate devices across different IL systems. A slope close to 1 and a correlation coefficient (r) close to 1 indicate strong agreement.
Precision: Acceptably low variability (Within run %CV and Between Run %CV) for both normal and abnormal controls.

Performance Metric	Specific Criterion (Implied for Substantial Equivalence)	Reported Device Performance
Method Comparison (New vs. Predicate HemosIL Factor XII Deficient Plasma on ACL Family)
ACL 3000 (n=71)	Slope ≈ 1, r ≈ 1	Slope: 0.9284, r: 0.9882
ACL 10000 (n=71)	Slope ≈ 1, r ≈ 1	Slope: 0.9116, r: 0.9704
ACL Advance (n=70)	Slope ≈ 1, r ≈ 1	Slope: 1.0065, r: 0.9687
ACL TOP (n=72)	Slope ≈ 1, r ≈ 1	Slope: 1.0739, r: 0.9551
Method Comparison (New vs. Predicate Hemoliance Factor XII Deficient Plasma on ELECTRA)
E1600C (n=73)	Slope ≈ 1, r ≈ 1	Slope: 0.9918, r: 0.9863
Within Run Precision (%CV)	Low %CV for both normal and abnormal controls
ACL 9000 Normal Control		1.9 %CV
ACL 9000 Special Test Control Level 2		2.6 %CV
ACL Futura Normal Control		3.0 %CV
ACL Futura Special Test Control Level 2		2.3 %CV
ACL TOP Normal Control		4.7 %CV
ACL TOP Special Test Control Level 2		6.1 %CV
ELECTRA 1600C Normal Control		3.4 %CV
ELECTRA 1600C Special Test Control Level 2		3.5 %CV
Between Run Precision (%CV)	Low %CV for both normal and abnormal controls
ACL 9000 Normal Control		3.4 %CV
ACL 9000 Special Test Control Level 2		3.3 %CV
ACL Futura Normal Control		2.9 %CV
ACL Futura Special Test Control Level 2		3.8 %CV
ACL TOP Normal Control		3.1 %CV
ACL TOP Special Test Control Level 2		3.2 %CV
ELECTRA 1600C Normal Control		7.8 %CV
ELECTRA 1600C Special Test Control Level 2		4.3 %CV

Study Information

Sample size used for the test set and the data provenance:
- Sample Size (Method Comparison): Approximately 70-73 citrated plasma samples per comparison (e.g., 71 for ACL 3000, 70 for ACL Advance, 73 for ELECTRA 1600C).
- Sample Size (Precision): Not explicitly stated how many unique samples were used to create the controls, but precision was assessed over multiple runs (n=80) for each instrument and control type.
- Data Provenance: "In-house method comparison study." This suggests the data was generated by the manufacturer, likely in a controlled laboratory setting. The country of origin is not specified, but the manufacturer is based in Lexington, MA, USA. The study appears to be prospective for the new device as it's being compared to established predicates.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable. This device is an in vitro diagnostic (IVD) for quantitative determination of factor XII activity, not an image-based diagnostic or clinical decision support system that relies on expert human interpretation for ground truth. The "ground truth" (or reference standard) in this context is the measurement obtained from the predicate devices.
Adjudication method for the test set:
- Not applicable. As above, this is an IVD device measuring a quantitative value, not subject to expert adjudication in the way an imaging study or qualitative diagnostic might be. The comparison is objective, based on measured values.
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 an IVD device, not an AI-assisted diagnostic tool that involves human readers interpreting results.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is a standalone device. Its performance is evaluated directly on patient samples (or controls) by comparing its measurements to those of predicate devices. The "algorithm" here is the biochemical assay and the instrument's processing of the reaction, without human interpretation as a performance variable.
The type of ground truth used:
- For the method comparison, the "ground truth" or reference standard for comparison was the measurements obtained from the predicate devices (HemosIL Factor XII Deficient Plasma on ACL Family and Hemoliance Factor XII Deficient Plasma on ELECTRA). These are established, legally marketed devices.
- For precision, the ground truth is against the statistical mean of the measurements themselves, for "Normal Control" and "Special Test Control Level 2" materials.
The sample size for the training set:
- Not applicable in the typical sense of machine learning. This device functions as a biochemical assay, not an AI/ML model that requires a "training set" to learn from data. Its performance is based on the inherent chemical and biological principles of the assay and its manufacturing quality, not a learned algorithm.
How the ground truth for the training set was established:
- Not applicable for the reasons stated above.

Summary

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K043559

Section 3 HemosIL Factor XII Deficient Plasma - 510(k) Summary (Summary of Safety and Effectiveness)

Submitted by:

Instrumentation Laboratory Co. 113 Hartwell Avenue Lexington, MA 02421 Phone: 781-861-4467 781-861-4207 Fax:

Contact Person:

Carol Marble, Regulatory Affairs Director Phone: 781-861-4467 / Fax: 781-861-4207

Summary Prepared:

December 14, 2004

Name of the Device:

HemosIL Factor XII Deficient Plasma

Regulatory Information:

Regulation Section:	Factor Deficiency Test (864.7290)
Classification:	Class II
Product Code:	GJT
Panel:	Hematology

Identification of Predicate Device(s):

K893534	Hemoliance Factor XII Deficient Plasma on ELECTRA Series Analyzers
K002400	HemosIL Factor XII Deficient Plasma* on ACL Family of Analyzers
*NOTE: FDA cleared as part of the each ACL instrument 510(k): for
example, the ACL Advance (K002400)

Description of the Device/Intended Use(s):

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

Statement of Technological Characteristics of the Device Compared to Predicate Device:

The new HemosIL Factor XII Deficient Plasma is substantially equivalent to Hemoliance Factor XII Deficient Plasma (on ELECTRA Series Analyzers) and HemosIL Factor XII Deficient Plasma (on ACL Family of Analyzers) in performance, intended use and safety and effectiveness.

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Section 3 HemosIL Factor XII Deficient Plasma - 510(k) Summary (Summary of Safety and Effectiveness)

Summary of Performance Data:

Method Comparison

In an in-house method comparison study evaluating approximately 70 citrated plasma samples, the slopes and correlation coefficients (r) for HemosIL Factor XII Deficient Plasma versus the predicate devices are shown below:

NOTE: HemosIL APTT-SP and SynthASil were used as the APTT reagents in testing.

New HemosIL Factor XII Deficient Plasma vs. Predicate HemosIL Factor XII Deficient Plasma on ACL Family

IL System	n	Slope	r
ACL 3000	71	0.9284	0.9882
ACL 10000	71	0.9116	0.9704
ACL Advance	70	1.0065	0.9687
ACL TOP	72	1.0739	0.9551

New HemosIL Factor XII Deficient Plasma vs. Predicate Hemoliance Factor XII Deficient Plasma on ELECTRA

IL System	n	Slope	r
E1600C	73	0.9918	0.9863

Within Run Precision

Within run and between run precision was assessed over multiple runs (n=80) on different instruments using a specific lot of APTT reagent (APTT-SP and SynthASil) and both normal and abnormal controls.

Instrument	Control	Mean% Factor XII	Within run%CV	Between Run%CV
ACL 9000	Normal Control	100.0	1.9	3.4
ACL 9000	Special Test Control Level 2	30.4	2.6	3.3
ACL Futura	Normal Control	95.1	3.0	2.9
ACL Futura	Special Test Control Level 2	31.4	2.3	3.8
ACL TOP	Normal Control	103.0	4.7	3.1
ACL TOP	Special Test Control Level 2	33.9	6.1	3.2
ELECTRA1600C	Normal Control	102.4	3.4	7.8
ELECTRA1600C	Special Test Control Level 2	36.0	3.5	4.3

HemosIL Factor XII Deficient Plasma 510(k)

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus, a symbol often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus.

FEB - 9 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Carol Marble Regulatory Affairs Director Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, Massachusetts 02421

Re: K043459

Trade/Device Name: HemosIL Factor XII Deficient Plasma Regulation Number: 21 CFR § 864.7290 Regulation Name: Plasma, coagulation deficient Regulatory Class: II Product Code: GJT Dated: December 14, 2004 Received: December 15, 2004

Dear Ms. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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Page 2 -

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

Robert L. Becker Jr.

Robert L. Becker, Jr., MD, PH.D Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: HemosIL Factor XII Deficient Plasma

Indications for Use:

Prescription Use
(Part 21 CFR 801 Subpart D)

Over-The-
(21 CFR 8

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K043459

HemosIL Factor XII Deficient Plasma 510(k)

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).