Reference Check is recommended for use in controlling the accuracy of quantitative hemostasis assays Reference Check is recommended for use in controlling the following parameters in the normal range:

Fibrinogen .
Factor II .
Factor V .
Factor VII .
Factor VIII:C
vWF: antigen ●
vWF: Ristocetin Cofactor ●
Factor IX ●
Factor X .
Factor XI .
Factor XII .
Factor XIII ●
Prekallikrein .
Protein C: antigen ●
Protein C: activity ●
Protein S: activity .
Protein S: total .
Protein S: free .
Antithrombin: activity ●
Antithrombin: antigen .
Alpha-2-antiplasmin .
Plasminogen .

Device Description

Reference Check is citrated human plasma collected from 20 or more carefully screened normal donors. Plasmas are pooled, buffered using 0.01M HEPES buffer, aliquoted and rapidly frozen.

AI/ML Overview

The provided text focuses on the 510(k) summary for "Reference Check," a normal control plasma, and strongly emphasizes its substantial equivalence to a predicate device, "Control Plasma N (K001256)." The information details the device's characteristics and its intended use for controlling the accuracy of quantitative hemostasis assays. However, it does not contain the specifics of a study proving the device meets acceptance criteria in the manner of a typical AI/ML device submission. Instead, the "study" is an argument for substantial equivalence.

Based on the provided text, here's an attempt to answer your questions, highlighting where information is absent for this type of medical device submission:

1. A table of acceptance criteria and the reported device performance

The acceptance criteria are implicitly met by demonstrating substantial equivalence to the predicate device. The performance is described in terms of its characteristics and intended use being similar to the predicate.

Acceptance Criteria (Implicit from Substantial Equivalence to Predicate)	Reported Device Performance (Reference Check)
Intended Use: Assayed Control - Normal	Assayed control for accuracy of quantitative hemostasis assays in the normal range.
Analytes Controlled: Fibrinogen, Coagulation factors II, V, VII, VIII, vWF: Antigen, vWF: Ristocetin Cofactor, IX, X, XI, XII, XIII, prekallikrein, Protein C (antigen and activity), Protein S (activity, total and free), antithrombin (antigen and activity), Alpha-2 antiplasmin, plasminogen	Controls Fibrinogen, Factor II, Factor V, Factor VII, Factor VIII:C, vWF: antigen, vWF: Ristocetin Cofactor, Factor IX, Factor X, Factor XI, Factor XII, Factor XIII, Prekallikrein, Protein C: antigen, Protein C: activity, Protein S: activity, Protein S: total, Protein S: free, Antithrombin: activity, Antithrombin: antigen, Alpha-2-antiplasmin, Plasminogen.
Matrix: Reagent from human plasma	Citrated human plasma collected from 20 or more carefully screened normal donors, pooled and buffered using 0.01M HEPES buffer.
Format: (Predicate is Lyophilized)	Frozen
Volume: 1 mL per vial	1 mL per vial

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

This information is not provided. The submission focuses on comparing the characteristics of the Reference Check product to a predicate device rather than presenting a performance study with a test set of data. The device itself is derived from "citrated human plasma collected from 20 or more carefully screened normal donors."

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)

This information is not provided. As this is a control plasma and not an AI/ML diagnostic device analyzing complex data, the concept of "experts establishing ground truth for a test set" does not directly apply in the usual sense. The "ground truth" for a control plasma is its assigned values for the analytes it controls, which would be established through laboratory methods and standardization.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

This information is not provided. Adjudication methods are typically relevant for studies involving human interpretation (e.g., of medical images) where discrepancies need resolution. This is not applicable to a control plasma product.

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

There was no MRMC study conducted. This type of study is relevant for AI/ML diagnostic tools that assist human readers, which Reference Check is not.

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

There was no standalone performance study in the context of an algorithm. Reference Check is a physical laboratory reagent, not an algorithm. Its "standalone" performance would be its stability, consistency, and assigned values, which are inherent to its manufacturing and quality control.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for a control plasma would be the assigned values (ranges) for the various analytes (e.g., Fibrinogen, Factor II, Protein C activity) determined through standardized laboratory assays. The document states both products are "assayed and provide reference ranges."

8. The sample size for the training set

This information is not applicable/provided. There is no "training set" in the context of a manufactured control plasma. Its characteristics are determined by the pooled human plasma used in its production.

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

This information is not applicable/provided. As above, there's no training set. The "ground truth" (assigned values) for the product is established through rigorous laboratory testing and calibration methods during its manufacture. The device description mentions it is "citrated human plasma collected from 20 or more carefully screened normal donors," indicating the source material for establishing its normal range.

Summary

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DEC 1 0 2001

510(K) Summary Reference Check

This summary of 510(k) safety and effectiveness information is being submitted in accordance

11 accordance of 510(k) safety and effective a 100 accord and CCCR 007 02 ro(K) Salety and Chock. Choos. Choose of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________ ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Submitters Name & Address:	Precision BioLogic Incorporated900 Windmill Road, Suite 100Dartmouth, Nova Scotia B3B 1P7Canada
Contact Name:	Stephen L. Duff – Director of New Business DevelopmentPhone: 902-468-6422 ext. 224Fax: 902-468-6421Email: sduff@precisionbiologic.com
Preparation Date:	November 7, 2001
Device Name & Classification:	Reference CheckCommon Name: Normal Control PlasmaClassification Name: Plasma, Control, NormalRegulatory Class II, 81 GIZ
Predicate Device:	Control Plasma N (K001256)Dade Behring Inc.Newark, Delaware 19714USA
Device Description:	Reference Check is citrated human plasma collected from 20 ormore carefully screened normal donors. Plasmas are pooled,buffered using 0.01M HEPES buffer, aliquoted and rapidly frozen.
Device Intended Use:	Reference Check is recommended for use in controlling theaccuracy of quantitative hemostasis assays in the normal range.

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Comparison to Predicate Device:

Parameter	Reference Check	Control Plasma N (K001256)
Intended Use	Assayed Control - Normal	Assayed Control - Normal
Analytes	Fibrinogen, Coagulation factors II, V,VII, VIII, vWF: Antigen, vWF: RistocetinCofactor, IX, X, XI, XII, XIII,prekallikrein, Protein C (antigen andactivity), Protein S (activity, total andfree), antithrombin (antigen andactivity), Alpha-2 antiplasmin,plasminogen	PT, aPTT, TT, Batroxobin time,Fibrinogen, Coagulation factors, II, V,VII, VIII, IX, X, XI, XII, XIII, VWFRistocetin Cofactor, Antithrombin III,Protein C, Protein S, Alpha-2antiplasmin, C1-inhibitor,Plasminogen, Lupus anticoagulants not available in the US
Matrix	Reagent from human plasma (citratedhuman plasma collected from 20 ormore carefully screened donors that ispooled and buffered using HEPESbuffer).	Reagent from human plasma(obtained from pooled plasmacollected from selected healthy blooddonors and stabilized with HEPESbuffer solution).
Format	Frozen	Lyophilized
Volume	1 mL per vial	1 mL per vial

Comments on Substantial Equivalence:

It is the opinion of Precision BioLogic Inc. that Reference Check is substantially equivalent to Control Plasma N (K001256), manufactured by Dade Behring Marburg GmbH, and currently marketed in the United States by Dade Behring Inc. This opinion is based on the following:

. Both products consist of pooled citrated normal human plasma
Both products are assayed and provide reference ranges for fibrinolytic and . coagulation parameters
Both products are intended for use in the accuracy and control of assays for . coagulation and fibrinolysis (i.e. hemostasis) in the normal range

Conclusion:

Reference Check is substantially equivalent to Control Plasma N.

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Image /page/2/Picture/0 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features an abstract image of an eagle with three curved lines representing its wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Stephen Duff Director of New Business Development Precision Biologic 900 Windmill Road, Suite 100 Dartmouth, N.S., Canada

DEC 1 0 2001

Re: K013708

Trade/Device Name: Reference Check Regulation Number: 21 CFR 864.5425 Regulation Name: Multipurpose system for in vitro coagulation studies Regulatory Class: Class II Product Code: GIZ Dated: November 7, 2001 Received: November 8, 2001

Dear Mr. Duff:

We have reviewed your Section 510(k) premarket notification of intent to market the device w o no re ro rowe 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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,

Steven Butman

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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Indications for Use Statement

510(k) Number:

K013708

Device Name:

Reference Check

Indications for Use:

Fibrinogen .
Factor II .
Factor V .
Factor VII .
Factor VIII:C �
vWF: antigen ●
vWF: Ristocetin Cofactor ●
Factor IX ●
Factor X .
Factor XI .
Factor XII .
Factor XIII ●
Prekallikrein .
Protein C: antigen ●
Protein C: activity ●
Protein S: activity .
Protein S: total .
Protein S: free .
Antithrombin: activity ●
Antithrombin: antigen .
Alpha-2-antiplasmin .
Plasminogen .

Josephine Buettner

(Division Syln-Off) (Division of Clinical Laboratory Deving of 510(k) Number ________________________________________________________________________________________________________________________________________________________________

Regulation Number and Section

§ 864.5425 Multipurpose system for in vitro coagulation studies.

(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.