The VisuLize™ Factor IX Antigen Kit is intended for use as an in vitro diagnostic assay for the quantitative determination of Factor IX antigen in human plasma samples and Factor IX concentrates using the double antibody enzyme linked immuno-sorbent assay (ELISA).

Device Description

The VisuLize™ Factor IX Antigen kit is a sandwich enzyme-linked immuno-sorbent assay (ELISA) using a polyclonal antibody coated 96-microwell format. Plasma samples are diluted and applied to the pre-coated wells. After washing away unbound proteins, a horseradish peroxidase (HRP) labelled polyclonal antibody is applied to detect the captured Factor IX. A chromogenic substrate (TMB containing H2O2) is added to allow for color development. The color formed is measured spectrophotometrically at 450 nm, with the absorbance being directly proportional to the concentration of Factor IX that was in the sample.

AI/ML Overview

Here's the breakdown of the acceptance criteria and the study details for the VisuLize Factor IX Antigen Kit, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria (Implied)	Reported Device Performance (VisuLize™ Factor IX Antigen Kit)	Predicate Device Performance (Asserachrom IX:AG Kit)
Intra-Assay Precision (CV%)	3.24% - 8.78%	5.31% - 5.84%
Inter-Assay Precision (CV%)	2.96% - 6.84%	5.99% - 6.39%
Linearity	Log-log curve, R² ≥ 0.990	Log-log graph (no specific R² mentioned)
Detection Limit	0.005 IU/mL (equivalent to 0.5%)	1%
Clinical Correlation (r)	Internal Testing: 0.987	Not applicable (this is a comparison metric)
P-value (ANOVA)	Internal Testing: 0.528	Not applicable (this is a comparison metric)
Clinical Correlation (r)	External Testing Site #1: 0.976	Not applicable (this is a comparison metric)
P-value (ANOVA)	External Testing Site #1: 0.458	Not applicable (this is a comparison metric)
Clinical Correlation (r)	External Testing Site #2: 0.982	Not applicable (this is a comparison metric)
P-value (ANOVA)	External Testing Site #2: 0.228	Not applicable (this is a comparison metric)

Note: The document does not explicitly state numerical acceptance criteria for the VisuLize kit. Instead, it demonstrates "substantial equivalence" to the predicate device by showing comparable or better performance for analytical metrics (precision, linearity, detection limit) and excellent correlation in clinical studies. The "acceptance criteria" are therefore inferred from the comparison to the predicate device, implying that performance similar to or better than the predicate is acceptable.

2. Sample Sizes Used for the Test Set and Data Provenance:

Internal Testing: 134 samples
External Testing Site #1: 114 samples
External Testing Site #2: 109 samples
Total Test Set Sample Size: 357 samples (134 + 114 + 109)
Data Provenance: The document states "Testing of clinical samples across the clinical range was conducted internally and by two external testing sites." It doesn't explicitly state the country of origin for the samples or whether they were retrospective or prospective, but the company is based in Ancaster, ON, Canada, hinting at Canadian origin for internal testing. The external sites are not specified geographically. Given this is a 510(k) summary, it's highly likely these were retrospective samples from stored banks, or an observational study, rather than a prospective clinical trial, focused on method comparison.

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

This information is not provided in the document. For an immunoassay like this, the "ground truth" for the clinical performance comparison is the result obtained from the predicate device (Asserachrom IX:AG Kit). The study compares the results of the proposed device to the predicate device, assuming the predicate device provides the established "truth" for Factor IX antigen levels. It doesn't involve expert consensus on the diagnosis of a condition but rather the measurement of an analyte.

4. Adjudication Method for the Test Set:

This information is not applicable and not provided. Adjudication typically refers to resolving discrepancies between multiple readers or diagnostic methods for qualitative assessments (e.g., presence/absence of a disease). In this quantitative assay, the comparison is made between two analytical methods, and statistical measures like Pearson correlation and ANOVA are used to assess agreement, not adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size:

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study focuses on human readers' performance with and without AI assistance, which is not relevant for a standalone in-vitro diagnostic (IVD) kit that quantitatively measures an analyte. The study conducted was a method comparison study between a new IVD kit and a legally marketed predicate IVD kit.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, a standalone performance study was done. The VisuLize™ Factor IX Antigen Kit is an in-vitro diagnostic assay. Its performance (precision, linearity, detection limit, and correlation with the predicate) was evaluated based on the kit's direct output, without human interpretation or intervention in the measurement itself. The human involvement is limited to performing the assay according to instructions and interpreting the quantitative result.

7. The Type of Ground Truth Used:

The "ground truth" for the clinical performance comparison was the quantitative Factor IX Antigen measurements obtained from the predicate device, the Asserachrom IX:AG Kit. The study aimed to show that the new device produced results consistent with an already legally marketed and accepted device.

8. The Sample Size for the Training Set:

The document does not provide information about a specific "training set" or its sample size. For an ELISA kit, "training" is more about optimizing the assay components and protocol during development rather than training a machine learning model on a distinct dataset. The presented data are for validation/testing of the finalized kit's performance against the predicate.

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

As there is no explicit mention of a "training set" in the context of machine learning, this question is not applicable. The development of the assay would have involved standard laboratory practices for optimizing reagent concentrations, incubation times, wash steps, etc. The "ground truth" during this development phase would have been established through internal validation experiments, likely using reference materials and potentially comparing early versions of the assay to existing methods, but this is not explicitly detailed as a formal "training set" with established ground truth in the context of this 510(k) submission.

Summary

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K05105-54

JUN 2 9 2005

Section H

510(k) Summary for VisuLize™ Factor IX Antigen Kit (Summary of Safety and Effectiveness)

This summary of 510(k) safety and effectiveness information is being submitted in Sammary of STO(K) Sarety in ments of SMDA 1990 and 21 CFR 807.92.

Submitted By:	Affinity Biologicals Inc.1395 Sandhill DriveAncaster, ONCanada, L9G 4V5Phone: 905-304-9896Fax: 905-304-9897
Contact Person:	Denise Foulon, Scientific DirectorPhone: 905-304-9896Fax: 905-304-9897
Summary Prepared:	April 25, 2005
Name of the Device:	VisuLize™ Factor IX Antigen KitCommon Name: Factor IX ELISA assay
Classification of Device:	Class II21 CFR 864.7290, Factor Deficiency TestSubpart H, Hematology Kits and PackagesProduct Code: GGP
Predicate Device:	Asserachrom IX:AG, K854312Diagnostica Stago (formerly American Bioproducts)
Device Description:	The VisuLize™ Factor IX Antigen kit is a sandwich enzyme-linked immuno-sorbent assay (ELISA) using a polyclonalantibody coated 96-microwell format. Plasma samples arediluted and applied to the pre-coated wells. After washing awayunbound proteins, a horseradish peroxidase (HRP) labelledpolyclonal antibody is applied to detect the captured Factor IX. Achromogenic substrate (TMB containing H2O2) is added to allowfor color development. The color formed is measuredspectrophotometrically at 450 nm, with the absorbance beingdirectly proportional to the concentration of Factor IX that was inthe sample.
Device Intended Use:	The VisuLize™ Factor IX Antigen Kit is an Enzyme Immunoassayfor the quantitative determination of Factor IX Antigen in humanplasma samples and Factor IX concentrates using the doubleantibody enzyme linked immuno-sorbent assay (ELISA).

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Comparison to Predicate Device:

following table:
	VisuLize™ Factor IX AntigenKit (Proposed Device)	Asserachrom IX:AG Kit(Predicate Device)
Assay Principle	Quantitative determination of FactorIX antigen by sandwich ELISA(polyclonal - polyclonal HRP)	Quantitative determination of FactorIX antigen by sandwich ELISA(polyclonal - polyclonal HRP)
Intended Use	An enzyme immunoassay for thequantitative determination of FactorIX antigen in human plasma samplesand Factor IX concentrates using thedouble antibody enzyme linkedimmuno-sorbent assay (ELISA).	An enzyme immunoassay (EIA)procedure for the quantitativedetermination of Factor IX by thesandwich technique also known asenzyme-linked immunosorbentassay (ELISA).
Sample Matrix	Human plasma derived from bloodcollected into 3.2% buffered citrate	Human plasma derived from bloodcollected into 3.2% buffered citrate
Intra-assayprecision (CV%)	3.24% - 8.78%	5.31% - 5.84%
Inter-assayprecision (CV%)	2.96% - 6.84%	5.99% - 6.39%
Linearity	Log-log curve, R2 ≥ 0.990	Log-log graph
Detection Limit	0.005 IU/mL (0.5%)	1%
Traceability ofCalibrator Plasma	Calibrator plasma is standardizedagainst a secondary standard that istraceable to the WHO InternationalStandard for Factor IX Activity99/826	Calibrator plasma is standardizedagainst a secondary standard that istraceable to the WHO InternationalStandard for Factor IX Activity99/826

A technical comparison of the proposed device and the predicate device is illustrated in the

Clinical Performance Comparison:

The clinical performance of the VisuLize™ Factor IX Antigen Kit versus the Asserachrom IX:AG rine oliniour performance of the substantial equivalence. Testing of clinical samples across the kir was confider range was conducted internally and by two external testing sites. The results ohtained by the three testing sites demonstrated excellent correlations between the proposed and predicate devices, as illustrated in the following table:

Summary of all Clinical Data from 3 Testing Sites

	INTERNALTESTING	EXTERNAL TESTINGSITE #1	EXTERNAL TESTINGSITE #2
Number of Samples	134	114	109
Pearson ProductMoment correlation co-efficient (r)	0.987	0.976	0.982
P-value (Single factorANOVA)	0.528	0.458	0.228

Conclusion: Based on the technical comparison and clinical performance results, it is concluded that the VisuLize™ Factor IX Antigen kit is substantially equivalent to the Asserachrom IX:AG enzyme immunoassay.

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JUN 2 9 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Denise Foulon Scientific Director Affinity Biologicals Inc. 1395 Sandhill Drive Ancaster, ON Canada, L9G 4V5

Re: K051054

Trade/Device Name: VisuLize™ Factor IX Antigen Kit Regulation Number: 21 CFR § 864.7290 Regulation Name: Factor Deficiency Test Regulatory Class: II Product Code: GGP Dated: April 25, 2005 Received: April 26, 2005

Dear Ms. Foulon:

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 L. Becker Jr.

Robert L. Becker, Jr., MD, PH. 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): K051054

Device Name: VisuLize™ Factor IX Antigen Kit

Indications for Use:

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ AND/OR (21 CFR 807 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)

Souchesi Buntuta
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) Kos1054

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).