HemosIL Protein C is an in vitro diagnostic test for the quantitative determination of Protein C in human citrated plasma based on a synthetic chromogenic substrate. Protein C deficiency is associated with recurrent venous thrombosis, especially in young adults. Acquired deficiencies of Protein C are associated with hepatic disorders, oral anticoagulant therapy and disseminated intravascular coagulation.

Device Description

HemosIL Protein C is an in vitro diagnostic test for the quantitative determination of Protein C in human citrated plasma based on a synthetic chromogenic substrate.

AI/ML Overview

This documentation is a 510(k) premarket notification for a modification to an existing device, the HemosIL Protein C. The core device itself remains unchanged; the submission is specifically about modifying the "Expected Values" section of the product insert. Therefore, the traditional acceptance criteria and performance study as one might expect for a new device or significant modification are not present in this document.

Here's an analysis based on the provided text, focusing on the reason for this specific submission:

1. Table of Acceptance Criteria and Reported Device Performance:

Based on the nature of this 510(k) submission, the "acceptance criteria" are not related to a specific numerical performance metric of the device's accuracy or precision. Instead, the acceptance criteria implicitly revolve around:

Consistency with established medical literature: The modified insert references a published normal range.
Emphasis on local laboratory validation: The insert reinforces the need for each laboratory to establish its own normal range due to variables.
Lack of material difference: The core regulatory acceptance criterion for this submission is that the device with the modified insert is not materially different from the FDA-cleared predicate device K980875.

Acceptance Criterion (Implicit for this type of submission)	Reported Device Performance (as per submission)
The device, with the modified product insert, is not materially different from the predicate device K980875.	The submission asserts this directly: "HemosIL Protein C with the modified Expected Values section in the product insert is not materially different from the FDA cleared device." The FDA's clearance implies agreement with this statement for the specific change submitted. The core technology and function of the assay remain identical.
The modified "Expected Values" section accurately reflects established medical knowledge regarding Protein C levels.	The insert states: "Protein C activity levels in healthy individuals are approximately in the range of 70 - 140%. Protein C levels are low in neonates and increase to adult levels during adolescence." This is supported by a citation from published literature: Kottke-Marchant K, Comp P. Laboratory Issues in Diagnosing Abnormalities of Protein C, Thrombomodulin, and Endothelial Cell Protein C Receptor, Arch Pathol Lab med 2002; 126:1337-1348.
The modified "Expected Values" section appropriately warns users about the need for local laboratory validation of normal ranges.	The insert clearly states: "Due to many variables which may affect results, each laboratory should establish its own normal range."

No traditional performance study (e.g., sensitivity, specificity, accuracy against a gold standard) was conducted or presented in this document because the device itself and its underlying technology are not changing. The study referenced (Kottke-Marchant K, Comp P. et al.) is external published literature used to support the content of the modified insert, not a study conducted by the device manufacturer for this specific 510(k).

The rest of the questions pertain to performance studies and are not applicable to this specific submission, which is purely an administrative change to labeling based on existing knowledge.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective): Not applicable, as no new performance study was conducted. The reference information is from published medical literature.

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, as no new performance study was conducted. The ground truth for the "Expected Values" is based on the consensus found in the cited medical literature, which is peer-reviewed.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not applicable, as no new performance study was conducted.

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 an in vitro diagnostic test, not an AI-enabled diagnostic imaging device or similar system involving human interpretation of results in a comparative study.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: Not applicable. The HemosIL Protein C is a laboratory assay.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc): For the modified label content, the ground truth is expert consensus/published medical literature.

8. The sample size for the training set: Not applicable, as no new performance study or AI algorithm was being trained.

9. How the ground truth for the training set was established: Not applicable, as no new performance study or AI algorithm was being trained.

Summary

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K062430

SEP - 1 2006

Submitted by:

Instrumentation Laboratory Company 113 Hartwell Avenue Lexington, MA 02421

Contact Person:

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

Summary Prepared:

August 18, 2006

Name of the Device:

HemosIL Protein C

Regulatory Information:

	864.7290 Factor Deficiency Test	Class II
81GGP	Test, Qualitative and Quantitative Factor Deficient

Identification of Predicate Device(s):

K980875 HemosIL Protein C

Device Description:

ﺔ

Reason for Submission:

The Expected Values section of the HemosIL Protein C insert is being modified to reference a normal range from published literature, reinforcing the need for each laboratory to establish its own normal [reference] range due to the many variables which may affect results.

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

HemosIL Protein C with the modified Expected Values section in the product insert is not materially different from the FDA cleared device.

Summary of Expected Values Section to the Modified Product Insert:

Protein C activity levels in healthy individuals are approximately in the range of 70 - 140%. Protein C levels are low in neonates and increase to adult levels during adolescence.*

Due to many variables which may affect results, each laboratory should establish its own normal range.

Kottke-Marchant K, Comp P. Laboratory Issues in Diagnosing Abnormalities of Protein C, Thrombomodulin, and * Endothelial Cell Protein C Receptor, Arch Pathol Lab med 2002; 126:1337-1348.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/1/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle. The seal is black and white.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

EP - 1 2006

Re: K062430

Trade/Device Name: HemosIL Protein C Regulation Number: 21 CFR § 864.7290 Regulation Name: Factor Deficiency Test Regulatory Class: II Product Code: GGP Dated: August 18, 2006 Received: August 21, 2006

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 Beckerh

Robert L. Becker, Jr., MD, Pa 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): K062430

Device Name: HemosIL Protein C

Indications for Use:

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)

Josephine Bautista

Division Sign Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K062430

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).