HemosIL Fibrinogen-C is intended for the quantitative determination of fibrinogen, based on the Clauss method, in human citrated plasma on IL Coagulation Systems. For in vitro diagnostic use.

Device Description

The Fibrinogen-C kit uses an excess of thrombin to convert fibrinogen to fibrin in diluted plasma. At high thrombin and low fibrinogen concentration, the rate of reaction is a function of the fibrinogen concentration.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the HemosIL Fibrinogen-C device, based on the provided text:

Acceptance Criteria and Device Performance for HemosIL Fibrinogen-C

The submission details modifications to the HemosIL Fibrinogen-C test parameters on the ACL TOP system. The study aims to demonstrate that these modified parameters are substantially equivalent to the previously marketed device.

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a separate set of pass/fail thresholds. Instead, it presents the performance of both the "Current Parameters" (predicate device) and the "Modified Parameters" (new device) for comparison, implying that similar or improved performance for the modified parameters constitutes acceptance.

Performance Characteristic	Current Parameters (Predicate Device Performance)	Modified Parameters (Reported Device Performance)	Implied Acceptance Criteria (Goal)
Interference			No significant increase in interference compared to predicate.
Heparin	Up to 1 U/mL (no interference)	Up to 1 U/mL (no interference)	$\le$ 1 U/mL (no interference)
Hemoglobin	Up to 375 mg/dL (no interference)	Up to 375 mg/dL (no interference)	$\le$ 375 mg/dL (no interference)
Triglycerides	Up to 890 mg/dL (no interference)	Up to 750 mg/dL (no interference)	Comparable or better than predicate
Bilirubin	Up to 21 mg/dL (no interference)	Up to 21 mg/dL (no interference)	$\le$ 21 mg/dL (no interference)
Fibrinogen Degradation Products (FDP)	Up to 100 µg/mL (no interference)	New testing showed interference from FDP. Insert will indicate results "may be affected."	Acknowledge and communicate any interference.
Precision (Within Run CV)			Comparable or better precision than predicate.
Normal Control Level	7.9% @ 365 mg/dL	4.5% @ 303 mg/dL	$\le$ 7.9% (ideally lower)
Low Fibrinogen Control Level	7.7% @ 93 mg/dL	5.1% @ 107 mg/dL	$\le$ 7.7% (ideally lower)
Linearity	80 - 700 mg/dL	35 - 1000 mg/dL	Expanded to 35 - 1000 mg/dL

Note on FDP Interference: For FDP, the acceptance criteria are not to maintain "no interference" but rather to accurately characterize and communicate any newly identified interference. The modified parameters identified interference at FDP levels where the current parameters showed none (up to 100 µg/mL), leading to an update in the product insert.

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

The document does not specify the exact sample sizes used for the test sets contributing to the performance data (interference, precision, and linearity).

The document does not explicitly state the data provenance (e.g., country of origin of the data, retrospective or prospective). However, given that this is a 510(k) submission for a medical device in the US, it is implied that the studies were conducted under appropriate regulatory guidelines, likely in the US, and typically involve prospective testing for performance characteristics.

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

This type of in vitro diagnostic (IVD) device (fibrinogen determination) does not typically involve "experts establishing ground truth" in the same way imaging or clinical diagnostic devices might. Instead, the "ground truth" for performance studies of IVD assays is established by:

Reference Methods: For accuracy and linearity, the "ground truth" would be established by comparing the device's measurements to a known, highly accurate reference method or gravimetric/volumetric preparation of analytes.
Known Concentrations: For precision studies, specific control levels (Normal, Low Fibrinogen) with known target concentrations are used.
Spiked Samples: For interference studies, potentially interfering substances are added to samples at known concentrations.

Therefore, no information on the number or qualifications of "experts" for ground truth establishment is provided, as it's not applicable in the traditional sense for this kind of device.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1 or 3+1) are typically used for subjective assessments, such as interpreting medical images or clinical outcomes, where human expert consensus is needed. For an IVD device like HemosIL Fibrinogen-C, which provides quantitative measurements, formal adjudication by experts is not applicable. The measurements are objective and evaluated against established analytical performance metrics.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are used to evaluate the diagnostic performance of devices (often imaging-based AI) when interpreted by multiple human readers, often comparing performance with and without AI assistance. This device is an in vitro diagnostic assay that produces a quantitative result, not an interpretation requiring human readers in the MRMC sense.

6. Standalone Performance (Algorithm Only)

Yes, a standalone performance assessment was effectively done. The performance data presented (interference, precision, linearity) directly reflects the capabilities of the HemosIL Fibrinogen-C reagent and the ACL TOP system's analytical process, independent of human interpretation or intervention beyond standard laboratory procedures for operating the instrument and running the assay. The "algorithm" here refers to the optimized test parameters, incubation time, and math model.

7. Type of Ground Truth Used

The type of ground truth for these studies would be based on:

Analytical Measurement Standards: For linearity and accuracy, traceable reference materials or highly characterized plasma samples with known fibrinogen concentrations.
Known Fibrinogen Concentrations: For precision, commercially prepared control materials with assigned target values.
Spiked Interferent Concentrations: For interference studies, specific concentrations of potentially interfering substances (Heparin, Hemoglobin, Triglycerides, Bilirubin, FDP) added to plasma samples.

The document does not explicitly state the specific reference methods or standards used, but these are standard practices for IVD validation.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" or its sample size. For an IVD like HemosIL Fibrinogen-C, the "training" analogous to an AI model would be the development and optimization of the assay parameters, calibration levels, incubation time, and math model. This ongoing development process happens internally, often involving numerous experiments, but these are generally not characterized as a distinct "training set" in regulatory submissions, which focus on the final validation data.

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

As with the "test set" ground truth, for the optimization/development (analogous to "training") phase of an IVD, the ground truth would be established through a combination of:

Analytical Chemistry Principles: Ensuring the Clauss method is accurately implemented.
Reference Materials: Using validated reference materials for calibration and early performance checks.
Methodology Development: Iteratively testing and refining parameters (e.g., thrombin concentration, reaction time, dilution protocols, mathematical models) to achieve desired analytical performance characteristics (sensitivity, specificity, linearity, precision) against known standards and characterized samples.

The specific details of this internal development process for establishing ground truth are not provided in this 510(k) summary, which focuses on the final validation results.

Summary

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K073367

Submitted by:

Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02421

Contact Person:

Carol Marble, Regulatory Affairs Director Phone No .: 781-861-4467 Fax No .: 781-861-4207

Prepared:

November 29, 2007

Device Name:

HemosIL Fibrinogen-C

Regulatory Information:

KQJ	System, Fibrinogen Determination
864.7340	Fibrinogen Determination System	Class II

Predicate Device:

K931721 HemosIL Fibrinogen-C

Device Intended Use:

HemosIL Fibrinogen-C is intended for the quantitative determination of fibrinogen, based on the Clauss method, in human citrated plasma on IL Coagulation Systems.

Device Description:

Reason for Submission:

The HemosIL Fibrinogen-C test parameters on the ACL TOP are being modified as follows:

. Separate low-end and high-end reflex test parameters are being added to expand the linearity claims on the ACL TOP from the current labeled 80-700 mg/dL to 35-1000 mg/dL.
. The calibration levels are now prepared by aspirating the calibrator directly from the calibrator vial (direct dilution instead of serial dilution).
The robustness of the assay is increased by optimizing the incubation time and math model. .

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

The performance of the optimized test parameters for HemosIL Fibrinogen-C on the ACL TOP is substantially equivalent to the performance of the current legally marketed test parameters.

. There are no changes in the reagent's intended use, formulation or operating principle and no changes to the instrument system software, intended use, operating principle or labeled performance claims with this submission.
DEC 2 7 2007

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510(k) Summary (Cont.)

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Summary of Performance Data:

Limitations
Current Parameters			Modified Parameters
No Interference
•	Heparin	Up to 1 U/mL	•	Heparin	Up to 1 U/mL
•	Hemoglobin	Up to 375 mg/dL	•	Hemoglobin	Up to 375 mg/dL
•	Triglycerides	Up to 890 mg/dL	•	Triglycerides	Up to 750 mg/dL
•	Bilirubin	Up to 21 mg/dL	•	Bilirubin	Up to 21 mg/dL
•	Fibrinogen Degradation ProductsUp to 100 µg/mL		•	Fibrinogen Degradation Products:New testing showed interference from FDP.Therefore, the insert will indicate thatFibrinogen-C assay results on the ACL TOPmay be affected by degradation products(fibrin or fibrinogen) in the plasma assayed.This statement is consistent with thelanguage already in use for the other ACLinstrument platforms. An associatedliterature reference regarding FDPinterference will be added.
Precision
Current Parameters			Modified Parameters
Control Level	Mean	Within Run CV		Control Level	Mean	Within Run CV
Normal	365 mg/dL	7.9%		Normal	303 mg/dL	4.5%
Low Fibrinogen	93 mg/dL	7.7%		Low Fibrinogen	107 mg/dL	5.1%
Linearity
Current Parameters			Modified Parameters
80 - 700 mg/dL			35 - 1000 mg/dL

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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird symbol, with three curved lines forming its body and wings. The bird is positioned above a circular text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES, USA". The text is arranged around the circumference of the circle, with the bird symbol placed in the center.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 2 7 2007

Instrumentation Laboratory Co. C/O Carol Marble 113 Hartwell Avenue Lexington, Massachusetts 02421

Re: K073367

Trade/Device Name: Hemosil Fibrinogen-C Regulation Number: 21 CFR 864.7340 Regulation Name: Fibrinogen Determination System Regulatory Class: Class II Product Code: KQJ Dated: November 29, 2007 Received: November 30, 2007

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

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Page 2 - Instrumentation Laboratory Co.

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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (240) 276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Tabat Broderf

Robert L. Becker, Jr., M.D., 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 Fibrinogen-C

Indications for Use:

HemosIL Fibrinogen-C is intended for the quantitative determination of fibrinogen, based on the Clauss method, in human citrated plasma on IL Coagulation Systems.

For in vitro diagnostic use.

ﮯ Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use ____________ (21 CFR 801 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)

Jacqueline Bautista
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Ko73367

Special 510(k): HemosIL Fibrinogen-C

Regulation Number and Section

§ 864.7340 Fibrinogen determination system.

(a)
Identification. A fibrinogen determination system is a device that consists of the instruments, reagents, standards, and controls used to determine the fibrinogen levels in disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot).(b)
Classification. Class II (special controls). A control or fibrinogen standard intended for use with a fibrinogen determination system is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.