DIMENSION VISTA VITAMIN B12 AND FOLATE FLEX REAGENT CARTRIDGES AND LOCI 4 CALIBRATOR

K071224 · Dade Behring, Inc. · CDD · Nov 13, 2007 · Clinical Chemistry

Device Facts

• Record ID: K071224
• Device Name: DIMENSION VISTA VITAMIN B12 AND FOLATE FLEX REAGENT CARTRIDGES AND LOCI 4 CALIBRATOR
• Applicant: Dade Behring, Inc.
• Product Code: CDD · Clinical Chemistry
• Decision Date: Nov 13, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1810
• Device Class: Class 2

Intended Use

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 the Ferritin (FERR), Vitamin B12 (B12), and Folate (FOL) methods on the Dimension Vista® system.

Device Story

Dimension Vista B12 and Folate assays are homogeneous, competitive chemiluminescent immunoassays using LOCI technology. Input: human serum or plasma samples. Process: samples undergo pretreatment; binding proteins and Chemibeads (coated with analyte derivative and chemiluminescent dye) are added; Sensibeads (coated with streptavidin and photosensitizer dye) are added to form bead-pair immunocomplexes. Illumination at 680nm triggers singlet oxygen diffusion from Sensibeads to Chemibeads, inducing chemiluminescence measured at 612nm. Output: chemiluminescent signal inversely proportional to analyte concentration. Used in clinical laboratories on the Dimension Vista system. Results assist clinicians in diagnosing and managing anemias related to B12 or folate deficiency.

Clinical Evidence

Bench testing only. Split-sample method comparison performed against predicate ADVIA Centaur assays using clinical patient samples. B12 (n=124): slope 0.93, intercept -14.4 pg/mL, r=0.98. FOL (n=110): slope 1.02, intercept -0.07 ng/mL, r=0.96.

Technological Characteristics

Homogeneous competitive chemiluminescent immunoassay (LOCI technology). Reagents: synthetic chemibeads (coated with analyte derivative/chemiluminescent dye) and sensibeads (streptavidin-coated/photosensitive dye). Energy source: 680 nm light excitation. Detection: 612 nm chemiluminescence. Matrix: bovine serum albumin (calibrator). Automated system integration.

Indications for Use

Indicated for quantitative measurement of Vitamin B12 in human serum/plasma to diagnose/treat gastrointestinal malabsorption, and folate in human serum/plasma to diagnose/treat megaloblastic anemia. Used on Dimension Vista system.

Regulatory Classification

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.

Predicate Devices

• VB12 for the ADVIA Centaur® System (K041133)
• FOL for the ADVIA Centaur® system (K010050)
• FERR Calibrator for the Dimension system (K983548)

Submission Summary (Full Text)

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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 Piestrak<br>Dade Behring Inc.<br>P.O. Box 6101<br>Newark, DE 19714-6101 | |
|----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| Date of Preparation: | April 30, 2007 | |
| Name of Product: | 1. Dimension Vista® Vitamin B12 Flex® reagent cartridge (B12)<br>2. Dimension Vista® Folate Flex® reagent cartridge (FOL)<br>3. Dimension Vista® LOCI 4 Calibrator | |

#### FDA Classification Name:

1. 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:

| New<br>Product | Predicate<br>Device | 510(k)<br>number | Device<br>Class | Regulation | Product<br>Code |
|----------------------------------------------------------------|---------------------------------------------|------------------|-----------------|------------|-----------------|
| B12 Flex® reagent cartridge for<br>the Dimension Vista® system | VB12 for the ADVIA<br>Centaur® System | K041133 | II | 862.1810 | CDD |
| FOL Flex® reagent cartridge for<br>the Dimension Vista® system | FOL for the ADVIA<br>Centaur® system | K010050 | II | 862.1295 | CGN |
| LOCI 4 Calibrator for the<br>Dimension Vista® system | FERR Calibrator for the<br>Dimension 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 | Ferritin<br>ng/mL | B12<br>pg/mL | Folate<br>ng/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®<br>reagent cartridge | VB12 on the ADVIA<br>Centaur® 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 homogeneous<br>immunoassay | Competitive format heterogeneous<br>immunoassay |
| Detection | Chemiluminescent reaction<br>measurement at 680 & 612 nm | Chemiluminescent reaction<br>Wavelength 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®<br>reagent cartridge | FOL on the ADVIA<br>Centaur® 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 reaction<br>measurement at 680 & 612 nm | Chemiluminescent reaction<br>Wavelength not disclosed |
| Sample Size | 10 µL | 150 µL |
| Binding protein | Folate Binding Protein (FBP)<br>complexed with biotinylated mouse<br>monoclonal 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 4<br>Calibrator | Dimension® Ferritin Calibrator |
|---------------|-------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------|
| Intended Use | Calibrate Ferritin, Vitamin B12 and<br>Folate on the<br>Dimension Vista® system | Calibrate Ferritin on the<br>Dimension® clinical chemistry system |
| Analytes | Ferritin, Vitamin B12, Folate | Ferritin |
| Matrix | Bovine Serum Albumin | Bovine Serum Albumin |
| Traceable to: | WHO Standard for ferritin<br>3rd IS 94/572 and<br>USP material for B12, and Folate | WHO Standard for ferritin 3rd IS<br>94/572 |
| Form | Liquid stored @ -10 to -20°C | Liquid stored @ 2 to 8°C |
| Volume | A 2.5 mL per vial<br>B 1.5 mL per vial<br>C 1.0 mL per vial<br>D 1.0 mL per vial<br>E 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 | | | | | |
|---------------------------------------------------|---------------------------------------------|-------|-------------|--------------------------------|-----|
| Dimension<br>Vista® | Predicate | Slope | Intercept | Correlation<br>Coefficient (r) | n |
| B12 | VB12 for the<br>ADVIA<br>Centaur®<br>System | 0.93 | -14.4 pg/mL | 0.98 | 124 |
| FOL | FOL for the<br>ADVIA<br>Centaur®<br>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 [phone]. 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 [phone] or [phone] 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:

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.

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:

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.

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

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