The B12 Flex® reagent cartridge is an in vitro product for the quantitative measurement of Vitamin B12 in human serum and plasma on the Dimension® EXI" integrated chemistry system. Measurements of vitamin B12 are used in the diagnosis and treatment of anemias of the gastrointestinal malabsorption.

The FOL Flex® reagent cartridge is an in vitro product for the quantitative measurement of Folate in human serum on the Dimension® EXL™ integrated chemistry system. Measurements of folate are used in the diagnosis and treatment of megaloblastic anemia

Device Description

The B12 method is an in vitro diagnostic device that consists of pre-packaged reagents in a plastic eight well cartridge for use on the Dimension EXL™ integrated chemistry svstem. The vitamin B12 method is a homogeneous, competitive chemiluminescent immunoassay based on LOCl® technology. LOCI® 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 Sodium Hydroxide (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.

The FOL method is an in vitro diagnostic device that consists of pre-packaged reagents in a plastic eight well cartridge for use on the Dimension EXL™ integrated chemistry svstem. The Folate method is a homogeneous, competitive chemiluminescent immunoassay based on LOCI® technology. LOCI® 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 Sodium Hydroxide (NaOH) and Dithioerythritol (DTE) to release serum folate from endogenous folate binding protein (FBP) and to maintain 5-methyltetrahydrofolate 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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information based on the provided document:

Acceptance Criteria and Device Performance

The document describes two devices, the Dimension® EXL™ B12 and Dimension® EXL™ FOL Methods, and their substantial equivalence to predicate devices (Dimension Vista® B12 Flex and Dimension Vista® Folate Flex). The acceptance criteria are implicitly defined by the results of the method comparison studies, aiming to demonstrate strong correlation and agreement between the new devices and the predicate devices.

Table of Acceptance Criteria and Reported Device Performance

Metric	Acceptance Criteria (Implied by Predicate Performance)	Reported Dimension® EXL™ B12 Performance	Reported Dimension® EXL™ FOL Performance
Sample Type	Human serum and plasma	Human serum and plasma	Human serum and heparinized plasma
Technology	LOCI® technology	LOCI® technology	LOCI® technology
B12 Method Comparison
Slope	Close to 1.0	0.98	-
Y-intercept	Close to 0	19.0 pg/mL	-
Correlation (r)	High (close to 1.0)	0.995	-
FOL Method Comparison
Slope	Close to 1.0	-	1.01
Y-intercept	Close to 0	-	0.05 ng/mL
Correlation (r)	High (close to 1.0)	-	0.99

Study Proving Device Meets Acceptance Criteria

The study conducted was a split sample method comparison to demonstrate substantial equivalence to the legally marketed predicate devices.

Sample size used for the test set and the data provenance:
- Dimension® B12 Flex®: 233 human serum samples.
- Dimension® FOL Flex®: 138 human serum samples.
- Data Provenance: The document only states "human serum samples." It does not specify the country of origin or whether the data was retrospective or prospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. The "ground truth" in this context is the performance of the legally marketed predicate devices (Dimension Vista® B12 Flex and Dimension Vista® Folate Flex). The study compares the new device's performance against the established performance of the predicate.
Adjudication method for the test set: Not applicable. This was a method comparison study between two analytical instruments, not a study involving human interpretation or adjudication for ground truth.
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: Not applicable. This is not an AI-based diagnostic imaging device, but an in vitro diagnostic chemistry system.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: Yes, in effect. The study evaluated the performance of the new device (Dimension® EXL™ B12/FOL) as a standalone analytical instrument compared to the predicate device, both operating without human interpretation of results beyond standard laboratory practices. The "algorithm only" in this case refers to the automated immunoassay technology.
The type of ground truth used: The "ground truth" was effectively the measurements obtained from the legally marketed predicate devices (Dimension Vista® B12 Flex and Dimension Vista® Folate Flex). The study aimed to show that the new devices produced comparable results.
The sample size for the training set: Not applicable. This document describes a 510(k) submission for a new in vitro diagnostic test, specifically focusing on demonstrating substantial equivalence to a predicate device. It is not an AI model requiring a distinct "training set" in the machine learning sense. The development of such assays involves extensive R&D and calibration, but not typically a "training set" as defined for AI/ML.
How the ground truth for the training set was established: Not applicable, as no training set was explicitly mentioned or used in this context.

Summary

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FEB 1 2 2010

510(k) Summary for Dimension® EXL™ B12 and Dimension® EXL™ FOL Methods

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

The assigned 510(k) number is: _ 15 093 3 1

Manufacturer's Name, Address, Telephone, and Contact Person, Date of 1. Preparation:

Manufacturer:	Siemens Healthcare Diagnostics IncNewark, Delaware 19714-6101
Contact Information:	Siemens Healthcare Diagnostics Inc.500 GBC DriveP.O. Box 6101Newark, Delaware 19714-6101Attn: A. Kathleen EnnisTel: 302-631-9352Fax: 302-631-6299

November 17, 2009 Preparation date:

2. Device Name:

B12 Flex® Reagent Cartridge
Classification:	Class II
Product Code:	CDD
Panel:	Clinical Chemistry (75)

FOL Flex® Reagent Cartridge Classification: Class II Product Code: CGN Clinical Chemistry (75) Panel:

Identification of the Legally Marketed Device: 3.

Dimension Vista® B12 Flex Reagent Cartridge - K071224 Dimension Vista® Folate Flex Reagent Cartridge - K071224

CONFIDENTIAL

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Device Descriptions: 4.

B12

The B12 method is an in vitro diagnostic device that consists of pre-packaged reagents in a plastic eight well cartridge for use on the Dimension EXL™ integrated chemistry svstem.

The vitamin B12 method is a homogeneous, competitive chemiluminescent immunoassay based on LOCl® technology. LOCI® 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 Sodium Hydroxide (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.

Folate

The FOL method is an in vitro diagnostic device that consists of pre-packaged reagents in a plastic eight well cartridge for use on the Dimension EXL™ integrated chemistry svstem.

The Folate method is a homogeneous, competitive chemiluminescent immunoassay based on LOCI® technology. LOCI® 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 Sodium Hydroxide (NaOH) and Dithioerythritol (DTE) to release serum folate from endogenous folate binding protein (FBP) and to maintain 5-methyltetrahydrofolate 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.

5. Device Intended Uses:

The B12 method is an in vitro diagnostic test for the quantitative measurement of Vitamin B12 in human serum and plasma on the Dimension EXL™ integrated chemistry system.

The FOL method is an in vitro diagnostic test for the quantitative measurement of folate in human serum and plasma on the Dimension EXL ™ integrated chemistry system.

CONFIDENTIAL

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Siemens Healthcare Diagnostics Inc. B12 and Folate Special 510(k) Notification

Summary of the devices technological characteristics 6.

The Dimension B12 Flex® reagent cartridge has the same technological characteristics as the Dimension Vista ® B12 Flex reagent cartridge. A comparison of features is provided.

Feature	Predicate Device:	New Device:
	Dimension Vista® B12 Flex®reagent cartridge (K071244)	Dimension® B12 Flex®reagent cartridge
Intended Use	Both test systems are for in vitro diagnostic use for thequantitative measurement of B12 in human serum and plasma.	Both test systems are for in vitro diagnostic use for thequantitative measurement of B12 in human serum and plasma.
Sample Type	Both devices are for use with human serum and plasma.	Both devices are for use with human serum and plasma.
Analytical MeasuringRange	The Dimension Vista® B12method has an assay range of50 - 2000 pg/mL	The Dimension® B12 methodhas an assay range of 56 –2000 pg/mL
Technology	Both devices use LOCI® technology.	Both devices use LOCI® technology.
Sample size	Uses 15 µL of serum orplasma and has a dilution ratioof 1:11 in the extracting step.	Uses 12 µL of serum orplasma and has a dilution ratioof 1:10 in the extracting step.
Reagents	Both systems use the same reagents.	Both systems use the same reagents.
Instrument	The Dimension Vista® B12Flex® is run on the DimensionVista® System.	The Dimension® B12 Flex® isrun on the Dimension® EXLintegrated chemistry System.

The Dimension FOL Flex® reagent cartridge has the same technological characteristics as the Dimension Vista ® FOL Flex reagent cartridge. A comparison of features is provided.

Feature	Predicate Device:	New Device:
	Dimension Vista® FOL Flex®reagent cartridge (K071244)	Dimension® FOL Flex®reagent cartridge
Intended Use	Both test systems are for in vitro diagnostic use for thequantitative measurement of FOL in human serum and plasma.	Both test systems are for in vitro diagnostic use for thequantitative measurement of FOL in human serum and plasma.
Sample Type	Both devices are for use with human serum and heparinizedplasma.	Both devices are for use with human serum and heparinizedplasma.
Analytical MeasuringRange	The analytical measuring range for both methods is 0.5 – 20 ng/mL	The analytical measuring range for both methods is 0.5 – 20 ng/mL
Technology	Both devices use LOCI® technology.	Both devices use LOCI® technology.
Sample size	Both methods use 10 µL of sample.	Both methods use 10 µL of sample.
Reagents	Both systems use the same liquid reagents and has the samereaction concentrations for all reagents.	Both systems use the same liquid reagents and has the samereaction concentrations for all reagents.
	The Dimension Vista® FOLFlex® uses four (4), 70 mgtablets per well which containa total of 26 mg of DTE.	The Dimension FOL Flex®uses one (1), 95 mg tablet perwell which contains 26 mg ofDTE.
Instrument	The Dimension Vista® FOLFlex® is run on the DimensionVista® System.	The Dimension® FOL Flex® isrun on the Dimension® EXLintegrated chemistry System.

7. Method Comparison

A split sample method comparison was conducted using the Dimension® B12 Flex® reagent cartridge vs. the Dimension Vista® B12 Flex® reagent cartridge. Two hundred and thirty- three (233) human serum samples ranging from 68 to 1920 pg/mL were used.

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The data was analyzed using least squares linear regression. The analysis is as follows:

$$\mathsf{Slope} = \mathtt{0.98} \ \mathsf{y-intercept} = \mathtt{19.0} \text{ рэр/и} \ \mathsf{r} = \mathtt{0.995} \ \mathsf{n} = \mathtt{233}$$

A split sample method comparison was conducted using the Dimension® FOL Flex® reagent cartridge vs. the Dimension Vista® FOL Flex® reagent cartridge. One hundred and thirty- eight (138) human serum samples ranging from 0.6 to 19.2 ng/mL were . used. The data was analyzed using least squares linear regression. The analysis is as follows:

Slope= 1.01 y-intercept = 0.05 ng/mL r = 0.99 n = 138

1. Conclusion
  Based on a review of the devices technological features and the method comparison study, the Dimension® B12 Flex® reagent cartridge is substantially equivalent to the legally marketed device, the Dimension Vista® B12 Flex® reagent cartridge.

Based on a review of the devices technological features and the method comparison study, the Dimension® FOL Flex® reagent cartridge is substantially equivalent to the leqally marketed device, the Dimension Vista® FOL Flex® reagent cartridge.

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Image /page/4/Picture/0 description: The image shows the seal of the Department of Health & Human Services USA. The seal features the department's name encircling a stylized eagle-like symbol. The text is arranged in a circular fashion around the symbol. The symbol itself is composed of three curved lines that resemble a bird in flight.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Siemens Healthcare Diagnostics Inc. c/o Anna Marie Kathleen Ennis Regulatory Affairs Technical Specialist 500 GBC Drive, P.O. Box 6101 Newark, DE 19714, USA

FEB 1 2 2010

Re: K093631 Trade/Device Name: Dimension® B12 Flex® Reagent Cartridge and Dimension® FOL Flex® Reagent Cartridge Regulation Number: 21 CFR 862.1810 Regulation Name: Vitamin B12 Test System Regulatory Class: Class II Product Code: CDD and CGN Dated: January 15, 2009 Received: January 19, 2009

Dear Ms. Ennis

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 arior 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 thorers) maisions 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 I loast of advised that sour device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must of a comply with all r coolur statues and regularing, but not limited to: registration and listing (21 CFR Part 807); the rece of equirements, 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) This letter will anow you to began maine of substantial equivalence of your device to a legally premarket notification. The PDF Michig sification for your device and thus, permits your device to proceed to the market.

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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 postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Courtney C. Harper, Ph.D. 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 Form

K093631 510(k) Number (if known):

Dimension® B12 Flex® reagent cartridge Device Name:

Indications for Use:

ХХ Over-The-Counter Use Prescription Use Prescription Ose
(Part 21 CFR 801 Subpart D) AND/OR (21 CFR 801 Subpart C)

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

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

Carl Benarr

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K09 3631

Page 1 of 2

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Indications for Use Form

K093631 510(k) Number (if known):

Device Name: _ Dimension® FOL Flex® reagent cartridge_

Indications for Use:

Prescription Use ХХХХ Over-The-Counter Use Prescription Ose -------------------------------------------------------------------------------------------------------------------------------------------------------------(21 CFR 801 Subpart C)

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

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

Carol Benson

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K093631

Page 2 of 2

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.