Von Willebrand Reagent is used for the determination of ristocetin cofactor activity in human plasma. The determination of ristocetin cofactor activity is important in:

The diagnosis of Von Willebrand's disease.
The diagnosis of diseases characterized by changes in the ristocetin cofactor.
Pre-operative screening of haemorrhagic diatheses.

Device Description

The Von Willebrand Reagent consists of lyophilized platelets and ristocetin.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device called "Von Willebrand Reagent" by Behring Diagnostics. The key information for determining acceptance criteria and the study that proves the device meets them is in the "510(k) SUMMARY OF SAFETY AND EFFECTIVENESS" section (page 2).

Here's a breakdown of the requested information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" with pass/fail thresholds in a formal table format. However, it reports performance characteristics and compares them to a predicate device, implying these are the metrics used for demonstrating substantial equivalence. Acceptance is based on the substantial equivalence to the predicate device, Helena Laboratories Ristocetin Cofactor Assay.

Performance Characteristic	Acceptance Criteria (Implied by Comparison)	Reported Device Performance (Von Willebrand Reagent)
Comparative Analysis
Correlation Coefficient	High correlation to predicate device	0.94 (vs. predicate device)
Slope	Close to 1 (vs. predicate device)	0.97 (vs. predicate device)
Y-intercept	Close to 0 (vs. predicate device)	-4.4 (vs. predicate device)
Precision
Within-run precision	Acceptable range for diagnostic assay	6.1% to 16.2%
Total precision	Acceptable range for diagnostic assay	7.6% to 16.9%

2. Sample Size and Data Provenance for the Test Set

Sample Size for Test Set: A total of 70 patients (normal and pathological samples).
Data Provenance: Not explicitly stated, but given the manufacturer (Behring Diagnostics GmbH, Marburg, Germany) and contact information (San Jose, CA, USA), it's likely a prospective study conducted for regulatory submission. The country of origin of the data is not specified.

3. Number of Experts and their Qualifications for Ground Truth

This information is not provided in the document. The determination of "normal and pathological samples" for Von Willebrand disease is usually based on clinical diagnosis and often confirmed by laboratory tests, but the specific process for establishing ground truth for these specific samples (e.g., number of clinicians, their specialties, and experience) is not detailed.

4. Adjudication Method for the Test Set

This information is not provided in the document. For laboratory assays like this, ground truth is typically assessed by established diagnostic criteria and reference methods rather than expert adjudication in the same way as, for example, image interpretation.

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

No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic reagent, not an imaging device or AI-assisted diagnostic tool that would typically involve multiple human readers interpreting results. The comparison is between the new reagent and a predicate reagent.

6. Standalone Performance Study

Yes, a standalone performance study was done for the Von Willebrand Reagent. The "Comparative Analysis" and "Precision" sections describe the device's performance characteristics in determining ristocetin cofactor activity, independent of human interpretation or assistance beyond standard laboratory procedures.

7. Type of Ground Truth Used

The ground truth was based on clinical classification of "normal and pathological samples" combined with the results from the predicate device (Helena Laboratories Ristocetin Cofactor Assay), against which the new device's performance was compared using regression analysis.

8. Sample Size for the Training Set

The document does not mention a separate training set. For in-vitro diagnostic reagents of this type, the development often involves optimization and verification using various samples, but a formally defined "training set" in the context of machine learning is not applicable here. The 70 patients mentioned are for the comparative analysis and likely serve as the primary validation dataset.

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

As no separate training set is mentioned, this information is not applicable.

Summary

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Paul L. Rogers, Jr. Behring Diagnostics, Inc. 3403 Yerba Buena Road P.O. Box 49013 San Jose, California as 161

K972116 Re: Von Willebrand Reagent Regulatory Class: II Product Code: GGP Dated: June 4, 1997 Received: June 5, 1997

Dear Mr. Rogers:

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, 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 (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. ਸ 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 requlatory In addition, FDA may publish further announcements action. 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 Requlations.

Jul 2 5 1997

. . . .

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Page 2

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 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 and additionally 809.10 for in vitro diagnostic 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 regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other qeneral 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 (301) 443-6597 or at its internet address "http://www.fda.qov/cdrh/dsmamain.html".

Sincerely yours,
Steven Aitman

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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BEHRING

L. Behring

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS For Von Willebrand Reagent

1. Manufacturer and Contact Information:

JUL 25 1997 972116

Behring Diagnostics GmbH Manufacturer: P.O. Box 1149 35001 Marburg, Germany

Paul Rogers Contact Information: Behring Diagnostics Inc. 3403 Yerba Buena Road P.O. Box 49013 San Jose, CA 95161-9013 Tel: 408-239-2000

2. Device Classification Name:

The Von Willebrand Reagent is a Class II device and has a classification name of Test, Qualitative and Quantitative Factor Deficiency.

3. Intended Use:

The Von Willebrand Reagent is intended for the determination of the ristocetin cofactor activity in human plasma.

4. Device Description and Characteristics:

The Von Willebrand Reagent consists of lyophilized platelets and ristocetin. This is similar to the Helena Laboratories Ristocetin Cofactor Assay (the predicate device) which consists of a lyophilized Platelet Reagent and a lyophilized Ristocetin Reagent.

A total of 70 patients (normal and pathological samples) were Comparative Analysis: tested with the Von Willebrand Reagent and compared with the predicate device. Regression analysis of the test results gave a correlation coefficient of 0.94, a slope of 0.97, and a yintercept of -4.4.

Precision: Precision studies were performed following the NCCLS EP5 guideline using normal and pathological plasma samples. The within-run precision ranged from 6.1% to 16.2%. The total precision ranged from 7.6 to 16.9%.

છં.

પંચ Substantial Equivalence:

Behring Diagnostics Inc. considers Von Willebrand Reagent to be substantially equivalent to the Helena Laboratories Ristocetin Cofactor Assay in terms of intended use, reagent composition, and overall performance characteristics.

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510(k) Number (if known):

Von Willebrand Reagent Device Name:

Indications For Use:

Von Willebrand Reagent is used for the determination of ristocetin cofactor activity in human Volt Willebrand Reagent is of ristocetin cofactor activity is important in:

The diagnosis of Von Willebrand's disease. .
The diagnosis of diseases characterized by changes in the ristocetin cofactor. .
Pre-operative screening of haemorrhagic diatheses. .

Concurrence of CDRH,

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

Office of Device Evaluation (ODE)

(Division Sign-Off)Division of Clinical Laboratory Device
510(k) Number	K972216

Prescription Use
(Per 21 CFR 801.109)

Over-The-Crunter Use __

(Opennal Format 1-2-96)

్రామం

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).