NoFact VIII Deficient Plasma is a human plasma immunodepleted of Factor VIII and intended for the quantitative determination of Factor VIII activity in citrated plasma from patients suspected of FVIII deficiency. FVIII activity is based on the activated partial thromboplastin time. For in vitro diagnostic use.

Device Description

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the NoFact VIII Deficient Plasma device, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary for NoFact VIII Deficient Plasma focuses on demonstrating substantial equivalence to a predicate device (Stago VIII Deficient Plasma) through performance comparison and precision evaluation. While explicit "acceptance criteria" for each metric are not stated numerically, the narrative implies that the performance must be comparable to the predicate device and demonstrate acceptable precision.

Metric	Acceptance Criteria (Implied)	Reported Device Performance (NoFact VIII Deficient Plasma)
Comparative Performance	High correlation and agreement with predicate device.	Linear Regression: y = 0.8453x + 4.2111 (across all labs)
(NoFact vs. Predicate)	Slope close to 1, Intercept close to 0, R² close to 1.	R² = 0.9683 (across all labs)
		Site 1: Slope 0.861, Intercept 2.8, R² 0.991
		Site 2: Slope 0.914, Intercept 2.5, R² 0.986
		Site 3: Slope 0.831, Intercept 5.9, R² 0.953
Precision (CV%)	Acceptable precision for quantitative measurement methods.	Normal Control Plasma (91.6% FVIII): Within-run CV 4.2%, Lot-to-Lot CV 0.63%, Within-Device CV 6.8%
	(Often defined by CLSI guidelines or industry standards for similar assays)*	Abnormal Control Plasma (33.3% FVIII): Within-run CV 4.9%, Lot-to-Lot CV 3.8%, Within-Device CV 8.0%
		Low FVIII Pooled Patient Plasma (11.8% FVIII): Within-run CV 5.7%, Lot-to-Lot CV 0.0%, Within-Device CV 8.5%

Note: The document states "NoFact VIII Deficient Plasma provided acceptable precision" without numerical thresholds, implying adherence to general CLSI guidelines for precision for such assays.

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

Sample Size: 233 frozen plasma samples.
Data Provenance: The samples were analyzed across three different laboratories. The document does not specify the country of origin but implies a multi-site study within a regulatory context that often points to domestic (US) or internationally recognized sites. The data is retrospective as it refers to "frozen plasma samples."

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

This type of in vitro diagnostic device (IVD) for factor deficiency measurement typically does not use human experts to establish "ground truth" for individual samples in the way a diagnostic imaging AI might. Instead, the "ground truth" for the test set is established by the measurement of Factor VIII activity using the predicate device's reagent (Stago FVIII deficient plasma) coupled with the Stago PTT-A FVIII assay. The comparison is between the new device's performance and the established performance of the legally marketed predicate. Therefore, no experts were specifically used to establish ground truth in the context of interpretation or diagnosis for each sample.

4. Adjudication Method for the Test Set

As explained above, this study design compares the new device’s performance to an existing, validated method (the predicate device). There is no "adjudication" in the sense of resolving discrepancies between multiple human readers or between an AI and a human. The "ground truth" is the result obtained with the predicate device, and the new device's results are compared directly to those values.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic reagent, not an AI-powered diagnostic system that assists human readers in interpreting complex data like medical images. Therefore, the concept of "human readers improving with AI assistance" does not apply here.

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

Yes, in spirit, a standalone performance was done. The "NoFact VIII Deficient Plasma" is a reagent. Its performance is evaluated directly in an assay (Stago PTT-A FVIII assay) on an automated analyzer (STA Compact). The results (Factor VIII activity) are generated solely by the interaction of the sample, the reagent, and the analyzer, and then compared to the results obtained with the predicate reagent on the same analyzer using the same assay. There is no human "loop" involved in generating the primary measurement data, only in setting up the assay and validating the results.

7. The Type of Ground Truth Used

The ground truth used for performance comparison was the quantitative Factor VIII activity values obtained from the predicate device (Stago VIII Deficient Plasma) using the Stago PTT-A FVIII assay. This represents a "reference standard" established by an already legally marketed and validated assay.

8. The Sample Size for the Training Set

The document does not provide information on a "training set." This is typical for an in vitro diagnostic reagent. Reagents are generally developed and then their performance is validated against predicate devices or established methods. There isn't an "AI model" that requires a distinct training phase with labeled data in the same way an imaging algorithm would. The development (analogous to training) would involve optimizing the reagent's formulation and manufacturing processes, but this isn't detailed as a "training set" in the context of performance studies.

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

Since no specific "training set" is mentioned for an AI model, the concept of establishing ground truth for it is not applicable here. The focus is on validating the performance of the final reagent product against a recognized standard (the predicate device).

Summary

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510(k) Summary

This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K102851.

Applicant Name and Address 1)

Applicant:	r2 Diagnostics, Inc.
Address:	1801 Commerce DriveSouth Bend, IN 46628
Contact Person:	Marc D. Goldford
Phone #:	574-288-4377
Fax #:	574-288-2272
Email:	marc@r2diagnostics.com
Date of Preparation:	15 November 2010

2) Device Name(s)

Trade Name:	NoFact VIII Deficient Plasma
Classification Name:	Plasma, Factor Deficient (21CFR 864.7290, Product Code GJT

3) Predicate Device(s)

Stago VIII Deficient Plasma (K892859)

4) Device Description(s)

5) Intended Use(s)

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6) Technological Characteristic Summary

Comparison of the submitted kit and the predicate kit is summarized in the table below: a.

Comparison of submitted device NoFact VIII Deficient Plasma to
predicate device STA Deficient VIII
Similarities
Item	Submitted Device	Predicate Device
Intended use	NoFact VIII Deficient Plasmais a human plasmaimmunodepleted of Factor VIIIand intended for the quantitativedetermination of Factor VIIIactivity in citrated plasma frompatients suspected of FVIIIdeficiency. FVIII activity isbased on the activated partialthromboplastin time. For invitro diagnostic use.	STA Deficient VIII is animmunodepleted humanplasma intended for use in testsfor the determination of factorVIII activity in plasma byanalyzers of the STA linesuitable with this reagent.
Constituent material	Citrated human plasmaimmunodepleted of Factor VIII.	Citrated human plasmaimmunodepleted of Factor VIII.
Measurement principle	Diluted patient sample is mixedwith factor VIII deficient plasmaand then tested with an APTT.In these conditions the clottingtime of the mixture isdependent on theconcentration of FVIII in thepatient sample.	Diluted patient sample is mixedwith factor VIII deficient plasmaand then tested with an APTT.In these conditions the clottingtime of the mixture isdependent on theconcentration of FVIII in thepatient sample.
Format	Lyophilized plasma	Lyophilized plasma
Analyte being tested	Factor VIII activity	Factor VIII activity
Differences
Item	Submitted Device	Predicate Device
Reconstituted Stability	2-8C: 8 hrRT: 4 hr	2-8C: not listedRT: not listedOn-board STA Compact: 4 hrs

NoFact VIII Deficient Plasma was compared to the predicate STA FVIII Deficient plasma using the ﻘ Stago PTT-A FVIII assay on the STA Compact. Plasma samples were assayed in parallel with the Stago PTT-A assay using the STA FVIII deficient plasma ("Stago results"), and also with the same assay but where the NoFact VIII deficient plasma was substituted for the STA FVIII deficient plasma ("NoFact results"). A total of two hundred thirty three frozen plasma samples in three

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laboratories were analyzed. The linear regression equation of this comparison was: y = 0.8453x + 4.2111, with a coefficient of determination of 0.9683.

	All Labs	Site 1	Site 2	Site 3
	n=233	n=90	n=90	n=53
Slope	0.845 (0.825-0.865)	0.861 (0.844-0.878)	0.914 (0.891-0.936)	0.831 (0.777-0.884)
Intercept	4.2 (1.9-6.5)	2.8 (1.1-4.5)	2.5 (-0.1-5.1)	5.9 (-0.606-12.422)
R2	0.968	0.991	0.986	0.953

The regression statistics (with 95% confidence intervals for slope and intercept) by site were:

The Stago PTT-A FVIII assay was evaluated for precision with three lots of NoFact VIII Deficient ﻦ Plasma according to the CLSI guideline EP5-A2 "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-200 Edition":

Plasma	Mean FVIIIactivity, %	% CV, Within-run(S-r)	% CV, Lot-to-Lot(S-lot)	% CV, Within-Device(S-device)
System N(Normal ControlPlasma)n=240	91.6%	4.2%	0.63%	6.8%
System P(Abnormal ControlPlasma)n=240	33.3%	4.9%	3.8%	8.0%
Low FVIII pooledpatient plasman=120	11.8%	5.7%	0.0%	8.5%

NoFact VIII Deficient Plasma provided acceptable precision.

NoFact VIII Deficient Plasma is substantially equivalent to Stago VIII Deficient Plasma.

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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo consists of a circular arrangement of text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". Inside the circle is a stylized image of an eagle or bird-like figure with outstretched wings.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

r2 Diagnostics, Inc. c/o Mr. Marc D. Goldford Director, Research and Development 1801 Commerce Drive. South Bend, IN 46628

DEC 1 9 2011

Re: K102851

Trade/Device Name: NoFact VIII Deficient Plasma Regulation Number: 21 CFR § 864.7290 Regulation Name: Factor deficiency test Regulatory Class: Class II Product Code: GJT Dated: December 7, 2011 Received: December 8, 2011

Dear Mr. Goldford:

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 class II (Special Controls), 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter

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Page 2 - Mr. Marc D. Goldford

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.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803). please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Reena Philip

$f_{oh}$

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K102851

Device Name: NoFact VIII Deficient Plasma

Indications For Use: NoFact VIII Deficient Plasma is a human plasma immunodepleted of Factor VIII and intended for the quantitative determination of Factor VIII activity in citrated plasma from patients suspected of FVIII deficiency. FVIII activity is based on the activated partial thromboplastin time. For in vitro diagnostic use.

Prescription Use _ X (21 CFR Part 801 Subpart D)

And/Or Over the Counter Use_ (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K102851

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).