SIGMA DIAGNOSTICS FIBRINOGEN KIT (886A/887A) by SIGMA DIAGNOSTICS, INC.

The Sigma Diagnostics Fibrinogen Kit is a device used to determine the fibrinogen levels in disseminated intravascular coagulation (nonlocalized clotting within blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot).

Device Description

The method of Clauss measures the rate of fibrin conversion in the presence of excess thrombin and has been shown to be rapid, sensitive and precise. When diluted plasma is clotted with excess thrombin, the fibrinogen level is inversely proportional to the clotting time, vielding a curvilinear relationship when plotted on loglog paper. A calibration curve prepared from a fibrinogen reference is used to determine the fibrinogen concentration in the test sample.

AI/ML Overview

Here's an analysis of the provided text to extract information about the acceptance criteria and the study that proves the device meets them:

Device: Sigma Diagnostics Fibrinogen Determination Kit (Procedure No. 886/887)

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria Category	Specific Criteria (Target)	Reported Device Performance (Result)
Correlation with Predicate Device	Substantial equivalence to Sigma Diagnostics Fibrinogen Determination Kit, Procedure No. 880/881.	Correlation coefficient of 0.96 with a regression equation of y = 0.91x + 28.3 when compared to Procedure No. 880/881.
Precision (Within-Run)	Coefficient of Variation (CV) less than 5%	Within-run CV of less than 5%
Precision (Total)	Total precision of 6% or less	Total precision of 6% or less
Linearity	Not explicitly stated as a numerical target, but implied requirement for general clinical assay.	Determined to be linear to 1000 mg/dL
Range of Measurement	Not explicitly stated as a numerical target, but implied for clinical utility.	Tested with samples having fibrinogen concentrations ranging from 95 to 764 mg/dL.

2. Sample size used for the test set and the data provenance:

Sample Size: 102 samples
Data Provenance: Not explicitly stated, but the reference to "samples having fibrinogen concentrations ranging from 95 to 764 mg/dL" implies clinical samples. No information on country of origin or whether they were retrospective or prospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

Not applicable. The study is a comparison of two diagnostic kits, where one (Procedure No. 880/881) serves as the "established reagent" or reference method for the ground truth. There's no indication of human expert adjudication for individual sample results.

4. Adjudication method for the test set:

Not applicable. The ground truth was established by another "established reagent" (Sigma Diagnostics Fibrinogen Determination Kit, Procedure No. 880/881), not through expert adjudication.

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 not an AI-assisted device. It's an in-vitro diagnostic kit for fibrinogen determination.

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

Not applicable in the context of an algorithm. This device is a manual or semi-automated laboratory kit. The "standalone" performance is assessed by its direct measurements and comparison to a predicate device.

7. The type of ground truth used:

Comparative Ground Truth: The ground truth for this study was established using an "established reagent", specifically the Sigma Diagnostics Fibrinogen Determination Kit, Procedure No. 880/881. This means the new device (Procedure No. 886/887) was compared to an already accepted and marketed device.

8. The sample size for the training set:

No specific "training set" is mentioned as this device is not based on machine learning or AI. The study describes a verification and validation process against an existing method.

9. How the ground truth for the training set was established:

Not applicable, as there is no training set in the AI/ML sense. The "ground truth" for the performance evaluation was the results obtained from the predicate device (Procedure No. 880/881).

Summary

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K-11852

9 1997 nct

SUMMARY OF SAFETY AND EFFECTIVENESS FIBRINOGEN DETERMINATION KIT (PROC NO. 886/887)

Fibrinogen is the plasma protein precursor of fibrin, which when cross-linked, becomes the principal component of the fibrin clot. Thrombin cleaves fibrinogen to form a fibrin monomer. Fibrin monomers aggregate to form the insoluble fibrin polymers. Fibrinogen can be deficient in such conditions as congenital afibrinogenemia, hypofibrinogenemia and in some cases of dysfibrinogenemia. It can also be depressed in a number of disease states such as disseminated intravascular coagulation, systemic fibrinolysis, pancreatitis and severe hepatic dysfunction. Fibrinogen is an acute phase reactant protein whose concentration increases in response to many different physiological stimuli. It can be increased as a response to inflammatory states, with infections, during pregnancy and after trauma. It is elevated among smokers. 12 High fibrinogen levels in plasma have been associated with prethrombotic states. Fibrinogen levels have also been positively correlated to development of atherosclerotic cardiovascular disease and with the occurrence of myocardial infarction and stroke. 34 Because of the increased importance of the assessing fibrinogen levels, a reliable, sensitive procedure is necessary.

The method of Clauss measures the rate of fibrin conversion in the presence of excess thrombin and has been shown to be rapid, sensitive and precise.57 When diluted plasma is clotted with excess thrombin, the fibrinogen level is inversely proportional to the clotting time, vielding a curvilinear relationship when plotted on loglog paper. A calibration curve prepared from a fibrinogen reference is used to determine the fibrinogen concentration in the test sample.

The safety and effectiveness of Sigma Diagnostics Fibrinogen Determination Kit, Procedure No. 888/887 has been demonstrated by showing its substantial equivalence to Sigma Diagnostics Fibrinogen Determination Kit, Procedure No. 880/881. One hundred two samples having fibrinogen concentrations ranging from 95 to 764 mg/dL were assayed on the Fibrometer with the described reagent (y) and with an established reagent (x). Comparison of the results vielded a correlation coefficient of 0.96 and a regression equation of y = 0.91x + 28.3. Precision studies demonstrated a within-run CV of less than 5% and total precision of 6% or less. The Sigma Diagnostics Fibrinogen Kit, Procedure No. 886/887 has been determined to be linear to 1000 mg/dL.

REFERENCES

Day HJ, Arkin C F, Bovill EG, Bowie EJW, Carroll JJ, Joist JH, Lenahan JG, 1. Marlar RA, Triplett DA: Procedure for the Determination of Fibrinogen in Plasma; Approved Guideline. NCCLS Document H30-A. Villanova PA: National Committee for Clinical Laboratory Standards; 14(2): 1-13, 1994
1. Tan V, Doyle CJ, Budzynski: Comparison of the Kinetic Fibrinogen Assay With the von Clauss Method and the Clot Recovery Method in Plasma of Patients

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With Conditions Affecting Fibrinogen Coagulability. Am. J. Clin. Pathol. 104:455-462. 1995.

Kannel WB, Wolf PA, Castelli WP, D'Agostino RB. Fibrinogen and risk of 3. cardiovascular disease: The Framingham Study. JAMA 258:1183-1186, 1987.
Meade TW. Brozovic M. Chakrabarti RR, Haines AP, Imeson JD, Mellows S. 4. Miller GJ, North WRS, Stirling Y, Thrompson SG: Haemostatic Function and Ischaemic Heart Disease: Principal Results of the Northwick Park Heart Study. Lancet 2:533-537, 1987.
ട. Clauss. A: Gerinungs physiologische schnell Methods zur bestimmung des Fibrinogens. Acta Haematol 17:237, 1957
Koepke JA, Gilmer PH, Filip DJ et al: Studies of fibrinogen measurement in the 6. CAP survey program. Am J Clin Pathol 63:984, 1975
Bovill EG, McDonagh J, Triplett DA, Arkin CF, Brand JT, Hayes TE, Kaczmarek 7. E. Long T. Rock WA: Performance Characteristics of Fibrinogen Assays; Results of the College of American Pathologists Proficiency Testing Program 1988-1991. Arch, Pathol, Lab. Med, 117:58-66, 1993.

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Image /page/2/Picture/2 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" written around the perimeter. Inside the circle is an abstract image of an eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

William R. Gilbert, Ph.D. Manager, Scientific Affairs Sigma Diagnostics® 545 South Ewing Avenue St. Louis, Missouri 63103

Re: K971858 Fibrinogen Kit Trade Name: Regulatory Class: II Product Code: KQJ Dated: Auqust 6, 1997 Received: August 8, 1997

Dear Dr. Gilbert:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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, qood manufacturing practice, labeling, and prohibitions aqainst misbranding and adulteration.

OCT - 9 1997

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.

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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a leqally 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 and additionally 809.10 for in vitro diaqnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the requlation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page 1 __of __1

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: __ Sigma Diagnostics Fibrinogen Kit

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off) ( Division of Clinical Labor
Division of Clinical Labor
5100) 510(k) Number _

Over-The-Counter Use

Prescription Use ✓
(Per 21 CFR 801.109)

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.