The B12 Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of Vitamin B12 in human serum and plasma on the Dimension Vista® system. Measurements obtained by this device are used in the diagnosis and treatment of gastrointestinal malabsorption.

The FOL Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of folate in human serum and plasma on the Dimension Vista® system. Measurements obtained by this device are used in the diagnosis and treatment of megaloblastic anemia.

The LOCI 4 Calibrator is an in vitro diagnostic product for the calibration of Ferritin (FERR), Vitamin B12 (B12), and Folate (FOL) methods on the Dimension Vista® system.

Device Description

B12: The Dimension Vista® Vitamin B12 method is a homogeneous, competitive chemiluminescent immunoassay based on LOCTM technology. LOCT™ reagents include two synthetic bead reagents and biotinylated intrinsic factor (IF). The first bead reagent (Chemibeads) is coated with a B12 derivative and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. The patient sample is pretreated with NaOH to release the serum B12 from its carrier proteins. Potassium cyanide (KCN) is added to convert all the forms of B12 into a single, cyanocobalamin form, and dicyanocobinamide is added to keep the B12 from rebinding with the carrier proteins. After the sample pretreatment, the biotinylated IF and Chemibead reagents are added sequentially to the reaction vessel. Vitamin B12 from the sample competes with the B12-Chemibead for a limited amount of biotinylated IF. Sensibeads are then added and bind to the biotin to form bead pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of vitamin B12 in the sample.

FOL: The Dimension Vista® Folate method is a homogenous, competitive chemiluminescent immunoassay based on LOCT™ technology. LOCT™ reagents include two synthetic bead reagents and labeled folate binding protein (FBP). The first bead reagent (Chemibeads) is coated with a folic acid derivative and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. Before the immunological portion of the reaction is initiated, the patient sample is pretreated with NaOH and DTT to release serum folate from endogenous folate binding protein and to maintain 5-methyl tetrahydrofolate in its reduced form. After the sample pretreatment, Chemibeads and labeled folate binding reagent are added sequentially to the reaction vessel. Folate from the patient sample competes with the folate-Chemibead for a limited amount of labeled FBP. Sensibeads are then added and bind to the biotinylated portion of the labeled FBP to form bead pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of folate in the sample.

Calibrator: The Dimension Vista® LOCI 4 Calibrator is a five level, liquid calibrator. It is packaged as a kit of 10 vials, two vials each of five levels. The product matrix is 6% bovine serum albumin with buffer, stabilizer and preservatives. Level A is zero. Levels B through E contain Ferritin, Vitamin B12, and Folate at the following target concentrations: Level A: Ferritin 0 ng/mL, B12 0 pg/mL, Folate 0.0 ng/mL; Level B: Ferritin 26 ng/mL, B12 200 pg/mL, Folate 2.5 ng/mL; Level C: Ferritin 210 ng/mL, B12 500 pg/mL, Folate 5.0 ng/mL; Level D: Ferritin 1050 ng/mL, B12 1000 pg/mL, Folate 10.0 ng/mL; Level E: Ferritin 2000 ng/mL, B12 2100 pg/mL, Folate 21.0 ng/mL. Values are assigned to new lots from a masterpool that is referenced to the WHO standard for FERR, 3 14 IS 94/572 and United States Pharmacopoeia materials for B12 and Folate.

AI/ML Overview

This document describes the regulatory submission for three in-vitro diagnostic products: Dimension Vista® Vitamin B12 Flex® reagent cartridge (B12), Dimension Vista® Folate Flex® reagent cartridge (FOL), and Dimension Vista® LOCI 4 Calibrator. The submission aims to demonstrate substantial equivalence to previously cleared predicate devices.

1. Table of Acceptance Criteria and Reported Device Performance

For the Dimension Vista® B12 and FOL Flex® reagent cartridge assays, the acceptance criteria are implicitly based on demonstrating comparable performance (correlation, slope, and intercept) to their respective predicate devices. The reported performance is based on a split-sample comparison study.

Device/Assay	Acceptance Criteria (Implied by Predicate Comparison)	Reported Device Performance (vs. Predicate)
B12 Flex® reagent cartridge	Performance comparable to VB12 for ADVIA Centaur® System (similar correlation, slope, and intercept)	Slope: 0.93Intercept: -14.4 pg/mLCorrelation Coefficient (r): 0.98
FOL Flex® reagent cartridge	Performance comparable to FOL for ADVIA Centaur® System (similar correlation, slope, and intercept)	Slope: 1.02Intercept: -0.07 ng/mLCorrelation Coefficient (r): 0.96
LOCI 4 Calibrator	Calibrates Ferritin, Vitamin B12, and Folate methods on the Dimension Vista® system and is traceable to international standards (WHO, USP).	Traceable to WHO Standard for ferritin 3rd IS 94/572, and USP material for B12 and Folate.

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

The test set consisted of clinical patient samples.

B12: 124 clinical patient samples
FOL: 110 clinical patient samples

The data provenance is not explicitly stated in terms of country of origin but is referred to as "clinical patient samples," implying retrospective. The study type is a "split sample comparison" study, which means portions of the same patient sample were tested on both the new device and the predicate device.

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 in-vitro diagnostic comparative studies like this, the "ground truth" for individual patient samples is usually established by the predicate device's measurement, which is considered the established method. There is no mention of independent expert review of results or a separate ground truth determination method by experts.

4. Adjudication Method for the Test Set

This information is not applicable/provided as the study design is a direct comparison to a predicate device, not a classification task requiring adjudication of expert opinions.

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

This information is not applicable. The device is an in-vitro diagnostic assay for measuring biomarkers (Vitamin B12 and Folate) and a calibrator. It is not an imaging or diagnostic aid that would involve human "readers" or AI assistance in interpretation.

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

The performance data presented is for the standalone performance of the Dimension Vista® B12 and FOL Flex® reagent cartridge assays, as they are fully automated in-vitro diagnostic tests. There is no human interpretation component in the measurement itself, only in the clinical application of the results.

7. The Type of Ground Truth Used

The ground truth for the performance study (comparison to predicate) was established by the measurements obtained from the legally marketed predicate devices (VB12 and FOL assays on the ADVIA Centaur® System). This is a common approach for demonstrating substantial equivalence for in-vitro diagnostic devices.

8. The Sample Size for the Training Set

This information is not provided. As an in-vitro diagnostic reagent and calibrator kit, these devices do not typically have an "algorithm" in the sense of machine learning that requires a separate training set. Their development involves R&D and validation steps, but not a distinct "training set" like an AI product would.

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

This information is not provided and is generally not applicable in the context of these types of IVD reagent kits and calibrators. The development and manufacturing of these products involve rigorous quality control and calibration processes, often referenced to international standards, but not a "ground truth for a training set" in the common AI/machine learning sense.

Summary

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510(k) Summary of Safety and Effectiveness Information

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Submitter's Name:	Lorraine H PiestrakDade Behring Inc.P.O. Box 6101Newark, DE 19714-6101
Date of Preparation:	April 30, 2007
Name of Product:	1. Dimension Vista® Vitamin B12 Flex® reagent cartridge (B12)2. Dimension Vista® Folate Flex® reagent cartridge (FOL)3. Dimension Vista® LOCI 4 Calibrator

FDA Classification Name:

Radioassay, Vitamin B12 2. Acid, Folic, Radioimmunoassay 3. Calibrator

Predicate Device:

The following table describes the predicate device classification, regulation and product code associated with this pre-market notification:

NewProduct	PredicateDevice	510(k)number	DeviceClass	Regulation	ProductCode
B12 Flex® reagent cartridge forthe Dimension Vista® system	VB12 for the ADVIACentaur® System	K041133	II	862.1810	CDD
FOL Flex® reagent cartridge forthe Dimension Vista® system	FOL for the ADVIACentaur® system	K010050	II	862.1295	CGN
LOCI 4 Calibrator for theDimension Vista® system	FERR Calibrator for theDimension system	K983548	II	862.1150	JIX

Device Description:

B12

The Dimension Vista® Vitamin B12 method is a homogeneous, competitive chemiluminescent immunoassay based on LOCTM technology. LOCT™ reagents include two synthetic bead reagents and biotinylated intrinsic factor (IF). The first bead reagent (Chemibeads) is coated with a B12 derivative and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. The patient sample is pretreated with NaOH to release the serum B12 from its carrier proteins. Potassium cyanide (KCN) is added to convert all the forms of B12 into a single, cyanocobalamin form, and dicyanocobinamide is added to keep the B12 from rebinding with the carrier proteins. After the sample pretreatment, the biotinylated IF and Chemibead reagents are added sequentially to the reaction vessel. Vitamin B12 from the sample competes with the B12-Chemibead for a limited amount of biotinylated IF. Sensibeads are then added and bind to the biotin to form bead pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the

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Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of vitamin B12 in the sample. FOL

The Dimension Vista® Folate method is a homogenous, competitive chemiluminescent immunoassay based on LOCT™ technology. LOCT™ reagents include two synthetic bead reagents and labeled folate binding protein (FBP). The first bead reagent (Chemibeads) is coated with a folic acid derivative and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. Before the immunological portion of the reaction is initiated, the patient sample is pretreated with NaOH and DTT to release serum folate from endogenous folate binding protein and to maintain 5-methyl tetrahydrofolate in its reduced form. After the sample pretreatment, Chemibeads and labeled folate binding reagent are added sequentially to the reaction vessel. Folate from the patient sample competes with the folate-Chemibead for a limited amount of labeled FBP. Sensibeads are then added and bind to the biotinylated portion of the labeled FBP to form bead pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of folate in the sample. Calibrator

The Dimension Vista® LOCI 4 Calibrator is a five level, liquid calibrator. It is packaged as a kit of 10 vials, two vials each of five levels. The product matrix is 6% bovine serum albumin with buffer, stabilizer and preservatives. Level A is zero. Levels B through E contain Ferritin, Vitamin B12, and Folate at the following target concentrations :

Level	Ferritinng/mL	B12pg/mL	Folateng/mL
A	0	0	0.0
B	26	200	2.5
C	210	500	5.0
D	1050	1000	10.0
E	2000	2100	21.0

Values are assigned to new lots from a masterpool that is referenced to the WHO standard for FERR, 3 14 IS 94/572 and United States Pharmacopoeia materials for B12 and Folate

Intended Use:

B12

The B12 method is an in-vitro diagnostic test for the quantitative measurement of Vitamin B12 in human serum and plasma on the Dimension Vista® system.

FOL

The FOL method is an in-vitro diagnostic test for the quantitative measurement of folate in human serum and plasma on the Dimension Vista® system.

Calibrator

The LOCI 4 Calibrator is an in vitro diagnostic product for the calibration of the Ferritin (FERR), Vitamin B12 (B12), and Folate (FOL) methods on the Dimension Vista® system.

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Comparison to Predicate Device:

Both the Dimension Vitamin B12 Flex® reagent cartridge (B12) assay and the predicate VB12 assay on the ADVIA Centaur® System employ prepackaged reagents for use on automated clinical chemistry test systems. A comparison of the important similarities and differences of these methods is provided in the following table:

Feature	Dimension Vista® B12 Flex®reagent cartridge	VB12 on the ADVIACentaur® System
Intended Use	in vitro diagnostic use	in vitro diagnostic use
Sample Type	Serum and Plasma	Serum and Plasma
Assay Range	50 - 2000 pg/mL	45 - 2000 pg/mL
Technology	Competitive format homogeneousimmunoassay	Competitive format heterogeneousimmunoassay
Detection	Chemiluminescent reactionmeasurement at 680 & 612 nm	Chemiluminescent reactionWavelength not disclosed
Sample Size	15 µL	100 µL
Binding Protein	Purified porcine Intrinsic Factor	Purified porcine Intrinsic Factor

Both the Dimension Vista® Folate Flex® reagent cartridge (FOL) assay and the predicate Folate(FOL) assay on the ADVIA Centaur® System employ prepackaged reagents for use on automated clinical chemistry test systems. A comparison of the important similarities and differences of these methods is provided in the following table:

Feature	Dimension Vista® FOL Flex®reagent cartridge	FOL on the ADVIACentaur® System
Intended Use	in vitro diagnostic use	in vitro diagnostic use
Sample Type	Serum and Plasma	Serum and Red Blood Cells
Assay Range	0.5 - 20 ng/mL	0.35 - 24 ng/mL
Technology	Competitive format immunoassay	Competitive format immunoassay
Detection	Chemiluminescent reactionmeasurement at 680 & 612 nm	Chemiluminescent reactionWavelength not disclosed
Sample Size	10 µL	150 µL
Binding protein	Folate Binding Protein (FBP)complexed with biotinylated mousemonoclonal anti-FBP antibody	Biotinylated Folate Binding Protein

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Both the Dimension Vista® LOCI 4 Calibrator and the predicate Dimension® Ferritin Calibrator have similar intended use. A comparison of the important similarities and differences is provided in the following table:

Feature	Dimension Vista® LOCI 4Calibrator	Dimension® Ferritin Calibrator
Intended Use	Calibrate Ferritin, Vitamin B12 andFolate on theDimension Vista® system	Calibrate Ferritin on theDimension® clinical chemistry system
Analytes	Ferritin, Vitamin B12, Folate	Ferritin
Matrix	Bovine Serum Albumin	Bovine Serum Albumin
Traceable to:	WHO Standard for ferritin3rd IS 94/572 andUSP material for B12, and Folate	WHO Standard for ferritin 3rd IS94/572
Form	Liquid stored @ -10 to -20°C	Liquid stored @ 2 to 8°C
Volume	A 2.5 mL per vialB 1.5 mL per vialC 1.0 mL per vialD 1.0 mL per vialE 2.0 mL per vial	1 mL per vial
Levels	5 levels	5 levels

Note: The Dimension Vista® LOCI 4 Calibrator with Ferritin only is currently under review by FDA in K070552.

Comments on Substantial Equivalence:

Split sample comparison between the Dimension Vista® B12 and FOL Flex® reagent cartridge assays and ADVIA Centaur® system VB12 and FOL assay gave the following correlation statistics, when tested with clinical patient samples:

Dimension Vista® B12 and FOL vs. Predicate Method
DimensionVista®	Predicate	Slope	Intercept	CorrelationCoefficient (r)	n
B12	VB12 for theADVIACentaur®System	0.93	-14.4 pg/mL	0.98	124
FOL	FOL for theADVIACentaur®system	1.02	-0.07 ng/mL	0.96	110

Method Comparison Data

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Conclusion:

The Dimension Vista® Vitamin B12 and Folate Flex® reagent cartridge assays with the associated LOCI 4 Calibrator are substantially equivalent in principle and performance to the ADVIA Centaur VB12 and FOL assays based on the split sample comparison discussed above.

Lorraine Pestiak

Lorraine H Piestrak Regulatory Affairs & Compliance Manager April 30, 2007

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services (HHS). The logo features a stylized depiction of an eagle with its wings spread, symbolizing protection and care. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle emblem.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 1 3 2007

Dade Behring, Inc. c/o Ms Lorraine H Piestrak P.O. Box 6101 M/S 514 Newark, DE 19714

Re: K071224

Trade Name: Dimension Vista Vitamin B12 Flex reagent cartridge (B12), Dimension Vista Folate Flex reagent cartridge (FOL) and Dimension Vista LOCI 4 Calibrator Regulation Number: 21 CFR 862.1295 Regulation Name: Folic acid test system Regulatory Class: Class II Product Code: CDD, CGN and JIX

Dated: October 15, 2007 Received: October 22, 2007

Dear Ms Piestrak,

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).

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Page 2 -

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.

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) 276-0490. 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Cooper, M.S., D.V.M.

Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology 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):

Device Name: Dimension Vista® Vitamin B12 Flex® reagent cartridge (B12)

Indications For Use:

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson

Division Sign-

Office of In Vitao Diagnost Evaluation and Sa

10(k) K071224

Page 1 of

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Indications for Use

510(k) Number (if known):

Device Name: Dimension Vista® Folate Flex® reagent cartridge (FOL)

Indications For Use:

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benam

Division Sign-Off

Office of In Vitre Diagnostic " Evaluation and Safe

10(k) K0712-24

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Indications for Use

510(k) Number (if known):

Device Name: Dimension Vista® LOCI 4 Calibrator

Indications For Use:

The LOCI 4 Calibrator is an in vitro diagnostic product for the calibration of Ferritin (FERR), Vitamin B12 (B12), and Folate (FOL) methods on the Dimension Vista® system.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________ (21 CFR 801)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C. Benson

Division Sign-Off

Office of In Vita Cagreem Evaluation and Safety

.10(k) k67/224

Page 3 of 3

004

Regulation Number and Section

§ 862.1810 Vitamin B

12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.