HemosIL RecombiPlasTin is a high sensitivity thromboplastin reagent based on recombinant human tissue factor (RTF) for the quantitative in virro diagnostic determination in human citrated plasma of:

Prothrombin Time (PT) on IL Coagulation and ELECTRA Systems .
Fibrinogen on IL Coagulation Systems only .
The product is used for the evaluation of the extrinsic coagulation pathway and the monitoring of Oral Anticoagulant Therapy (OAT).

Device Description

HemosIL RecombiPlasTin is a high sensitivity thromboplastin reagent based on recombinant human tissue factor (RTF) for the quantitative in vitro diagnostic determination in human citrated plasma of:

Prothrombin Time (PT) on IL Coagulation and ELECTRA Systems .
. Fibrinogen on IL Coagulation Systems only
The product is used for the evaluation of the extrinsic coagulation pathway and the monitoring of Oral Anticoagulant Therapy (OAT).
The PT and fibrinogen parameter settings for HemosIL RecombiPlasTin on the ACL Futura and ACL Advance are being optimized for improved correlation with the ACL TOP, impacting the instrument-specific performance claims in the product insert.

AI/ML Overview

Here's an analysis of the provided text regarding the HemosIL RecombiPlasTin device, focusing on acceptance criteria, study details, and ground truth establishment:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device appear to be primarily focused on its analytical performance metrics, specifically method comparison (correlation coefficient and slope) and precision (CV%). The document compares the new parameter settings on the ACL Futura/Advance to a legally marketed predicate device on the ACL TOP.

Metric	Acceptance Criteria (Implied by Predicate Performance)	Reported Device Performance (HemosIL RecombiPlasTin with optimized parameters on ACL Advance)
Prothrombin Time (PT)
CV% (Within run)	Not explicitly stated (but shown for predicate)	Normal Control: 0.9%, Low Abnormal: 1.4%, High Abnormal: 1.4%
CV% (Total)	Not explicitly stated (but shown for predicate)	Normal Control: 1.3%, Low Abnormal: 2.3%, High Abnormal: 3.9%
Correlation Coefficient (r)	Close to 1.0 (High correlation with predicate)	0.9985
Slope	Close to 1.0 (Agreement with predicate)	1.039
Fibrinogen
CV% (Within run)	Not explicitly stated (but shown for predicate)	Not provided for Fibrinogen in this table
CV% (Total)	Not explicitly stated (but shown for predicate)	Not provided for Fibrinogen in this table
Correlation Coefficient (r)	Close to 1.0 (High correlation with predicate)	0.9811
Slope	Close to 1.0 (Agreement with predicate)	0.938

Note: The exact numerical acceptance criteria are not explicitly stated as "must be greater than X" or "less than Y." Instead, the performance values of the legally marketed predicate device (HemosIL RecombiPlasTin on ACL TOP and HemosIL Fibrinogen-C on ACL TOP) serve as the benchmark for substantial equivalence. The reported values demonstrate very strong correlation and close agreement with the predicate for both PT and Fibrinogen, indicating the device meets the implied acceptance criteria for equivalence.

2. Sample Size and Data Provenance for the Test Set

Sample Size for Test Set: 98 citrated plasma samples used for the method comparison study.
Data Provenance: Not explicitly stated (e.g., country of origin). The study involved "citrated plasma samples," which are human biological specimens. It's not specified if they were prospective or retrospective samples. As this is an in vitro diagnostic test for coagulation, the samples would likely be from a clinical setting, but further details are not provided.

3. Number of Experts and Qualifications for Ground Truth of the Test Set

This type of device (Prothrombin Time and Fibrinogen determination) relies on quantitative measurements, not subjective interpretation. Therefore, there are no "experts" in the traditional sense establishing a ground truth based on visual or interpretive assessment. The "ground truth" or reference method is the measurement obtained from the legally marketed predicate device (HemosIL RecombiPlasTin on ACL TOP for PT and HemosIL Fibrinogen-C on ACL TOP for fibrinogen).

4. Adjudication Method for the Test Set

Not applicable. As described above, the ground truth is established by a reference measurement from a predicate device, not through expert consensus or adjudication.

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

Not applicable.

This is an in vitro diagnostic (IVD) device, specifically a reagent for automated coagulation analyzers.
It does not involve human readers interpreting images or data in a way that would necessitate an MRMC study.
The comparison is between two automated systems (the new device on ACL Futura/Advance vs. the predicate on ACL TOP), not between human readers with and without AI assistance.

6. Standalone (Algorithm Only) Performance

Yes, this is essentially a standalone performance study. The HemosIL RecombiPlasTin reagent, when run on the ACL Futura/Advance, performs the measurements automatically. The reported performance metrics (precision, slope, correlation) represent the analytical performance of the optimized reagent-instrument combination without human intervention in the measurement process itself. The "comparison" is the standalone performance of the new configuration against the standalone performance of the predicate configuration.

7. Type of Ground Truth Used

The ground truth used is a reference measurement from a legally marketed predicate device. Specifically:

For Prothrombin Time (PT), the reference was the HemosIL RecombiPlasTin on the ACL TOP.
For Fibrinogen, the reference was the HemosIL Fibrinogen-C on the ACL TOP.
This is a common approach for demonstrating substantial equivalence for IVD devices, comparing the new device's measurements to those of an established, cleared device.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" in the context of machine learning or AI models. This device is a reagent with optimized parameters for existing instruments. The text states:
"The PT and fibrinogen parameter settings for HemosIL RecombiPlasTin on the ACL Futura and ACL Advance are being optimized for improved correlation with the ACL TOP, impacting the instrument-specific performance claims in the product insert."

This "optimization" process would involve internal development and testing to fine-tune the parameters. However, the specific size of the dataset used during this optimization phase is not provided in this 510(k) summary. The 98 plasma samples are explicitly described as being part of the method comparison study (which acts as the test set for regulatory submission).

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

As there isn't a "training set" in the common AI/machine learning sense, the ground truth for any internal optimization would likely have been established in a similar manner to the test set: by running control plasmas and potentially patient samples on the predicate device (ACL TOP) to define the target reference values that the optimized parameters on the new instruments (ACL Futura/Advance) aimed to match. The goal was to achieve "improved correlation with the ACL TOP."

Summary

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K043184

DEC 22 2004

Section 3 HemosIL RecombiPlasTin 510(k) Summary (Summary of Safety and Effectiveness)

Submitted by:

Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02421

Contact Person:

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

Summary Prepared:

November 16, 2004

Device Name:

HemosIL RecombiPlasTin

Classification Name:

864.7750	Prothrombin Time Test	Class II
81GJS	Test, Time, Prothrombin
864.7340	Fibrinogen Determination System	Class II
81GIS	Test, Fibrinogen

Legally Marketed Device:

K012768 HemosIL RecombiPlasTin

Device Description:

HemosIL RecombiPlasTin is a high sensitivity thromboplastin reagent based on recombinant human tissue factor (RTF) for the quantitative in vitro diagnostic determination in human citrated plasma of:

Prothrombin Time (PT) on IL Coagulation and ELECTRA Systems .
. Fibrinogen on IL Coagulation Systems only

The product is used for the evaluation of the extrinsic coagulation pathway and the monitoring of Oral Anticoagulant Therapy (OAT).

The PT and fibrinogen parameter settings for HemosIL RecombiPlasTin on the ACL Futura and ACL Advance are being optimized for improved correlation with the ACL TOP, impacting the instrument-specific performance claims in the product insert.

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

The performance of HemosIL RecombiPlasTin with optimized PT and fibrinogen parameter settings on the ACL Futura (K951891) and ACL Advance (K002400) is substantially Pauinalers to the performance of the current legally marketed device on the ACL TOP (K033414).

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Section 3 HemosIL RecombiPlasTin 510(k) Summary (Summary of Safety and Effectiveness)

Summary of Performance Data:

Within Run Precision

Within run and total precision assessed over multiple runs using three levels of control plasma for PT and two levels of control plasma for fibrinogen gave the following results:

Prothrombin Time (PT)	Mean (Seconds)	CV% (Within run)	CV% (Total)
Normal Control	11.6	0.9	1.3
Low Abnormal Control	30.3	1.4	2.3
High Abnormal Control	51.1	1.4	3.9

Method Comparison

In a method comparison study evaluating 98 citrated plasma samples, the slopes and correlation coefficients (r) are shown below for the legally marketed HemosIL RecombiPlasTin on an ACL Advance with optimized PT and fibrinogen parameters versus Hemos L RecombiPlasTin for PT and HemosIL Fibrinogen-C (K931721) for fibrinogen on the ACL TOP:

	Slope	r
PT (seconds)	1.039	0.9985
Fibrinogen (mg/dL)	0.938	0.9811

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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 depiction of an eagle or bird-like figure, composed of three curved lines that suggest wings or feathers. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged around the bird symbol in a circular fashion.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 22 2004

Ms. Carol Marble Regulatory Affairs Director Instrumentation Laboratory Co. 113 Hartwell Avenue Lexington, MA 02421

K043184 Re:

Trade/Device Name: HemosIL RecombiPlasTin- Optimized Parameter Settings on the ACL Futura/ ACL Advance

Regulation Number: 21 CFR 864.7750 Regulation Name: Prothrombin time set Regulatory Class: Class II Product Code: GJS Dated: December 6, 2004 Received: December 8, 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 (OS) 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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours,

Robert L. Becker Jr.

Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices 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 RecombiPlasTin - Optimized Parameter Settings on the ACL Futura/ACL Advance

Indications for Use:

HemosIL RecombiPlasTin is a high sensitivity thromboplastin reagent based on recombinant human tissue factor (RTF) for the quantitative in virro diagnostic determination in human citrated plasma of:

Prothrombin Time (PT) on IL Coagulation and ELECTRA Systems .
Fibrinogen on IL Coagulation Systems only .

The product is used for the evaluation of the extrinsic coagulation pathway and the monitoring of Oral Anticoagulant Therapy (OAT).

Prescription Use
(Part 21 CFR 801 Subpart D)

AND/OR

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

(OIVD)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices

Divis
Offic
Evalua.
510(k)	K043184

Regulation Number and Section

§ 864.7750 Prothrombin time test.

(a)
Identification. A prothrombin time test is a device used as a general screening procedure for the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin therapy (the administration of one of the coumarin anticoagulants in the treatment of venous thrombosis or pulmonary embolism).(b)
Classification. Class II (performance standards).