Access Vitamin B12

K223289 · Beckman Coulter, Inc. · CDD · Dec 23, 2022 · Clinical Chemistry

Device Facts

• Record ID: K223289
• Device Name: Access Vitamin B12
• Applicant: Beckman Coulter, Inc.
• Product Code: CDD · Clinical Chemistry
• Decision Date: Dec 23, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1810
• Device Class: Class 2

Intended Use

The Access Vitamin B12 assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of vitamin B12 levels in human serum and plasma (heparin) using the Access Immunoassay Systems. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.

Device Story

Access Vitamin B12 assay is a competitive binding immunoenzymatic assay; utilizes paramagnetic particles coated with goat anti-mouse IgG and mouse monoclonal anti-intrinsic factor; conjugate is intrinsic factor-alkaline phosphatase. Input: human serum or plasma samples. Process: two-step competitive chemiluminescent immunoassay performed on Dxl 9000 Access Immunoassay Analyzer. Output: quantitative vitamin B12 concentration (pg/mL). Used in clinical laboratory settings by trained technicians. Results assist clinicians in diagnosing and managing anemias related to gastrointestinal malabsorption.

Clinical Evidence

Bench testing only. Method comparison study (N=122) vs. predicate showed R2=0.97, slope 1.00 (95% CI 0.96-1.02). Imprecision study (N=84 per sample) demonstrated within-laboratory CV 2.7-7.7% for concentrations >100 pg/mL. Linearity verified across 68-1,500 pg/mL range. LoB 35 pg/mL, LoD 49 pg/mL, LoQ 49 pg/mL.

Technological Characteristics

Paramagnetic particle, chemiluminescent immunoassay. Solid phase: paramagnetic particles coated with goat anti-mouse IgG and mouse monoclonal anti-intrinsic factor. Conjugate: intrinsic factor-alkaline phosphatase. Two-step competitive binding principle. Automated analysis on Dxl 9000 system. Liquid ready-to-use reagent format. Standardization: USP Reference Material.

Indications for Use

Indicated for quantitative determination of vitamin B12 in human serum and plasma (heparin) to aid in diagnosis and treatment of anemias of gastrointestinal malabsorption.

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.

Submission Summary (Full Text)

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December 23, 2022

Beckman Coulter, Inc. Kuljeet Kaur Regulatory Affairs Manager 1000 Lake Hazeltine Drive Chaska, MN 55318-1084

## Re: K223289

Trade/Device Name: Access Vitamin B12 Regulation Number: 21 CFR 862.1810 Regulation Name: Vitamin B12 test system Regulatory Class: Class II Product Code: CDD Dated: October 25, 2022 Received: October 25, 2022

## Dear Kuljeet Kaur:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Digitally signed by Paula____ Caposino -S Date: 2022.12.23

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

510(k) Number (if known) k223289

Device Name Access Vitamin B12

#### Indications for Use (Describe)

The Access Vitamin B12 assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of vitamin B12 levels in human serum and plasma (heparin) using the Access Immunoassay Systems. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.

| Type of Use (Select one or both, as applicable) | |
|----------------------------------------------------------------------------|---------------------------------------------------------------------------|
| <div> <span> </span> Prescription Use (Part 21 CFR 801 Subpart D) </div> | <div> <span> </span> Over-The-Counter Use (21 CFR 801 Subpart C) </div> |

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Access Vitamin B12 510(k) Summary

510k Number: k223289

Date Prepared: December 23, 2022

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

### Submitted By:

Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318

### Contact Person:

Kuljeet Kaur, Ph.D Regulatory Affairs Manager Phone: [phone] Email: [e-mail]

### Device Name:

Common Name: Access Vitamin B12 Assay Trade Name: Access Vitamin B12 Classification Name: Vitamin B12 test system Classification Product Code: CDD Regulation: 21 CFR 862.1810

Predicate Device: Device Name: Access Vitamin B12 Assay 510(k) Number: k955436

### Device Description:

The Access Vitamin B12 assay is a competitive binding immunoenzymatic assay. The Access Vitamin B12 reagent kit is in a liquid ready-to-use format designed for optimal performance on Beckman Coulter's immunoassay analyzers. Each reagent kit contains two reagent packs. Other items needed to run the assay include substrate, calibrators, and wash buffer.

### Intended Use:

The Access Vitamin B12 assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of vitamin B12 levels in human serum and plasma (heparin) using the Access Immunoassay Systems. Measurements obtained by this device are used in the diaqnosis and treatment of anemias of gastrointestinal malabsorption.

#### Alternate Contact: Madhuri Boppana Senior Regulatory Affairs Analyst Email: [e-mail]

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| System<br>Attribute/Characteristic | Predicate Access Vitamin B12 on<br>Access Immunoassay System | Access Vitamin B12 on Dxl 9000<br>Access Immunoassay Analyzer |
|-------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------|
| Analyte Measured | Access Vitamin B12 | Same |
| Standardization | USP Reference Material | Same |
| Intended Use/ Indications<br>for Use | The Access Vitamin B12 assay is a<br>paramagnetic particle, chemiluminescent<br>immunoassay for the quantitative<br>determination of vitamin B12 levels in<br>human serum and plasma (heparin) using<br>the Access Immunoassay Systems. | Same |
| Solid Phase | Paramagnetic particles coated with goat<br>anti-mouse IgG; mouse monoclonal anti-<br>intrinsic factor | Same |
| Conjugate | Intrinsic factor-alkaline phosphatase | Same |
| Technology | Two-step competitive | Same |
| Format | Chemiluminescent | Same |
| Method | Automated | Same |
| Calibration | Utilizes a stored calibration curve | Same |
| Sample Type | Serum or plasma | Same |
| Reagent Pack formulation<br>and packaging | Access Reagent Pack formulation and<br>packaging. | Same |
| Stability | Stable at 2 to 10°C for 14 days after initial<br>use | Same |
| Substrate | Access Substrate | Lumi-Phos PRO Substrate |
| Measuring Range | 50 - 1,500 pg/mL (37 – 1,107 pmol/L) | 68 - 1,500 pg/mL (50 - 1,107<br>pmol/L) |
| Instrument | Access Immunoassay System | Dxl 9000 Access Immunoassay<br>Analyzer |

## Comparison of Technological Characteristics to the Predicate

# Summary of Studies:

## Method Comparison:

A method comparison study was completed to compare the Access Vitamin B12 assay on the Dxl 9000 Access Immunoassay Analyzer to the Access Vitamin B12 assay on the Access Immunoassay System using a protocol based on CLSI EP09c-A3. The results of the method comparison study met the acceptance criteria of R2 ≥ 0.90 and slope of 1.00 ± 0.14 and supports the equivalence of the Access Vitamin B12 assay on Dxl 9000 Access Immunoassay Analyzer to the Access Vitamin B12 assay on the Access instrument.

| N | Concentration<br>Range*<br>(pg/mL) | Slope | Slope<br>95% CI | Intercept | Intercept<br>95% CI | Correlation<br>Coefficient<br>R2 |
|-----|------------------------------------|-------|-----------------|-----------|---------------------|----------------------------------|
| 122 | 70 - 1248 | 1.00 | 0.96 - 1.02 | 6.1 | -0.16 - 15 | 0.97 |

*Range is Access values

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Imprecision: The imprecision study was run on three Dxl 9000 Access Immunoassay Analyzers, three reagent lots, and three calibrator lots. Six (6) serum samples, with varying Vitamin B12 concentrations, were assayed in duplicate with two runs per day, over 21 days. The assay was design to meet the requirements of imprecision of SD ≤ 12 pg/mL for values ≤ 100 pg/mL and CV ≤ 12.0 % for values > 100 pg/mL. The observed within-laboratory (total) % CV was between 2.7% and 7.7% for Vitamin B12 concentrations > 100 pg/mL. The withinlaboratory (total) SD was between 6 – 9 for Vitamin B12 concentrations ≤ 100 pg/ml. The results from a representative lot are as follows:

| Concentration (pg/mL) | | Repeatability<br>(Within-Run) | | Between-Run | | Between-Day | | Within-<br>Laboratory | | |
|-----------------------|----|-------------------------------|------|-------------|-----|-------------|------|-----------------------|-----|------|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 84 | 71 | 6 | 9.0 | 0 | 0.0 | 6 | 8.5 | 9 | 12.4 |
| Sample 2 | 84 | 102 | 5.9 | 5.8 | 1.0 | 1.0 | 5.1 | 5.0 | 7.9 | 7.7 |
| Sample 3 | 84 | 196 | 5.6 | 2.9 | 3.3 | 1.7 | 5.5 | 2.8 | 8.6 | 4.4 |
| Sample 4 | 84 | 435 | 9.2 | 2.1 | 9.4 | 2.2 | 10.3 | 2.4 | 16. | 3.8 |
| Sample 5 | 84 | 944 | 28.3 | 3.0 | 26. | 2.8 | 27.5 | 2.9 | 47. | 5.0 |
| Sample 6 | 84 | 1179 | 71.9 | 6.1 | 0.0 | 0.0 | 33.5 | 2.8 | 79. | 6.7 |

Linearity: A verification study was performed to determine the linearity of the Access Vitamin B12 assay on the Dxl 9000 Access Immunoassay Analyzer based on CLSI EP06-ED2. The results of this study met the acceptance criterion and indicate that the Access Vitamin B12 assay is linear on the Dxl 9000 Immunoassay System throughout the analytical measuring interval (68 - 1,500 pg/mL (50 - 1,107 pmol/L).

LoB/LoD: Verification studies were performed to determine the Limit of Blank (LoB) and Limit of Detection (LoD) of the Access Vitamin B12 assay using a protocol based on CLSI EP17-A2. The claimed LoB is 50 pg/mL (37 pmol/L). The assay is designed to meet the requirements for LoD ≤ 68 pg/mL (≤ 50 pmol/L). The results data demonstrate the LoB estimate of the vitamin B12 assay on Dxl 9000 is 35 pg/mL (26 pmol/L). The observed LoD of the Vitamin B12 assay on Dxl 9000 immunoassay analyzer is 49 pg/mL (36 pmol/L).

LoQ: Verification studies were performed to determine the Limit of Quantitation (LoQ) of the Access Vitamin B12 assay using a protocol based on CLSI EP17- A2 The assay is designed to meet the requirements for LoQ ≤ 68 pg/mL (≤ 50 pmol/L). The results data demonstrate the 20% CV LoQ estimate for the Access Vitamin B12 assay is 42 pg/mL. The results demonstrate the LoQ at 20% within laboratory (total) CV estimate of the Access Vitamin B12 assay to be 68 pg/mL. The maximum observed LoQ estimate for the Access Vitamin B12 assay on the Dxl 9000 immunoassay system is less than the reported LoD value (49 pg/mL).

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Following the CLSI EP17-A2 recommendation that the LoQ must be greater than or equal to LoD, the LoQ observed value is reported as 49 pg/mL.

Other claims: The claims for the analytical specificity, reference intervals, matrix comparison are being transferred from file k955436.

# Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access Vitamin B12 Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access Vitamin B12 Assay on the Access Immunoassay System as demonstrated through the information and data provided in this submission. The performance testing presented in this submission provides evidence that the device is safe and effective in its intended use.