Access Folate Assay

K223590 · Beckman Coulter, Inc. · CGN · Aug 23, 2023 · Clinical Chemistry

Device Facts

• Record ID: K223590
• Device Name: Access Folate Assay
• Applicant: Beckman Coulter, Inc.
• Product Code: CGN · Clinical Chemistry
• Decision Date: Aug 23, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1295
• Device Class: Class 2

Intended Use

The Access Folate assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of folic acid levels in human serum, lithium heparin plasma, and red blood cells using the Access Immunoassay Systems. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia. Folate levels in serum, lithium heparin plasma, and red blood cells are used to assess folate status. The serum folate levels is an indicator of recent folate intake. A low RBC folate value can indicate a prolonged folate deficiency.

Device Story

Access Folate assay is a chemiluminescent immunoassay for quantitative folic acid measurement in human serum, lithium heparin plasma, and red blood cells. For RBC testing, whole blood is pre-treated with an ascorbic acid lysing agent to hemolyze cells and convert polyglutamic folate to monoglutamic form. The assay uses a competitive binding principle: sample folate competes with folic acid-alkaline phosphatase conjugate for binding sites on folate binding protein. Complexes bind to paramagnetic particles coated with goat anti-mouse IgG. After magnetic separation and washing, a chemiluminescent substrate is added; light output, measured by a luminometer on the DxI 9000 Access Immunoassay Analyzer, is inversely proportional to folate concentration. Results are calculated via a stored multi-point calibration curve. RBC folate is derived by correcting for the 1:21 dilution and hematocrit. Used in clinical laboratories by trained personnel to assess folate status and diagnose megaloblastic anemia.

Clinical Evidence

Bench testing only. Precision studies (CLSI EP05-A3) evaluated repeatability and within-laboratory imprecision across serum and hemolysate matrices. Linearity (CLSI EP06-2nd ed) confirmed performance within the 2.0–24.8 ng/mL range. Method comparison (N=123 serum samples) between the DxI 9000 and the predicate Access 2 system showed a correlation coefficient (R) of 0.99 and a Passing-Bablok slope of 1.04. LoB, LoD, and LoQ were established per CLSI EP17-A2.

Technological Characteristics

Paramagnetic particle, chemiluminescent immunoassay; competitive binding principle. Automated system. Sample types: serum, lithium heparin plasma, red blood cells. Connectivity: DxI 9000 Access Immunoassay Analyzer. Substrate: Lumi-Phos PRO. Standardization: WHO International Standards. Calibration: stored curve.

Indications for Use

Indicated for quantitative determination of folic acid in human serum, lithium heparin plasma, and red blood cells to assess folate status and aid in the diagnosis and treatment of megaloblastic anemia in patients.

Regulatory Classification

Identification

A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.

Predicate Devices

• Access Folate on the Access Immunoassay Systems (K060774)

Submission Summary (Full Text)

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August 23, 2023

Beckman Coulter, Inc. Kuljeet Kaur Regulatory Affairs Manager 1000 Lake Hazeline Drive Chaska, Minnesota 55318

Re: K223590

Trade/Device Name: Access Folate Assay Regulation Number: 21 CFR 862.1295 Regulation Name: Folic Acid Test System Regulatory Class: Class II Product Code: CGN Dated: November 30, 2022 Received: July 27, 2023

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

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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 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 mediation-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,

# Marianela Perez-torres -S

Marianela Perez-Torres, Ph.D. Acting 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) K223590

Device Name Access Folate Assay

#### Indications for Use (Describe)

The Access Folate assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of folic acid levels in human serum, lithium heparin plasma, and red blood cells using the Access Immunoassay Systems. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia.

Folate levels in serum, lithium heparin plasma, and red blood cells are used to assess folate status. The serum folate levels is an indicator of recent folate intake. A low RBC folate value can indicate a prolonged folate deficiency.

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

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# Access Folate Assay 510(k) Summary

510(k) Number: k223590

Date Prepared: Aug 21, 2023

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

Kuljeet Kaur Regulatory Affairs Manager Phone: [phone] Email: [e-mail]

#### Alternate Contact:

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

Common Name: Folate test system Trade Name: Access Folate Assay Classification Name: Folic acid test system Classification Requlation: 21 CFR 862.1295 Classification Product Code: CGN

Predicate Device: Device Name: Access Folate Assay 510(k) Numbers: Primary predicate: k060774, Secondary predicate: k111952

#### Device Description:

The Access Folate assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of folic acid levels in human serum and lithium heparin plasma or red blood cells using the Access Immunoassay Systems.

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#### Intended Use:

The Access Folate assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of folic acid levels in human serum, lithium heparin plasma, and red blood cells using the Access Immunoassay Systems. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia.

Folate levels in serum, lithium heparin plasma, and red blood cells are used to assess folate status. The serum folate levels is an indicator of recent folate intake. A low RBC folate value can indicate a prolonged folate deficiency.

| System<br>Attribute/Characteristic | Predicate Access<br>Immunoassay Systems<br>(k060774) | Access Folate on Dxl<br>9000 Access<br>Immunoassay<br>Analyzer |
|-------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------|
| Intended Use/Indications<br>for Use | The Access Folate assay is a<br>paramagnetic particle,<br>chemiluminescent immunoassav<br>for the quantitative determination<br>of folic acid levels in human serum<br>and plasma (heparin) or red blood<br>cells using the Access<br>Immunoassay Systems. | Same |
| Analyte Measured | Access Folate | Same |
| Technology | Competitive binding Immunoassay<br>System | Same |
| Format | Chemiluminescent | Same |
| Method | Automated | Same |
| Calibration | Utilizes a stored calibration curve | Same |
| Sample Type | Serum, plasma, or red blood cells | Same |
| Stability | Stable at 2 to 10°C for 14 days<br>after initial use | Same |
| Instrument | Access 2 Immunoassay System | DxI 9000 Access<br>Immunoassay Analyzer |
| Substrate | Access Substrate | Lumi-Phos PRO |
| Measuring Range | 1.0 - 24.8 ng/mL | 2.0 - 24.8 ng/mL |

#### Comparison of Technological Characteristics to the Predicate

### Comparison of Technological Characteristics to the Predicate

| System<br>Attribute/Characteristic | Predicate Access<br>Immunoassay Systems<br>(k111952) | Access Folate on Dxl<br>9000 Access<br>Immunoassay Analyzer |
|------------------------------------|------------------------------------------------------------|-------------------------------------------------------------|
| Standardization | World Health Organization<br>(WHO) International Standards | Same |

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## Summary of Studies:

Method Comparison: The results of the within range method comparison study met the acceptance criteria of R2 ≥ 0.90 and slope 1.00 ± 0.12 and supports the equivalence of the Access Folate assay on Dxl 9000 to the predicate device, the Access Folate assay on Access 2 Instrument. The estimated bias at concentration corresponding to reference limits defined on the predicate system suggest that such values have not changed appreciably on the Dxl 9000 analyzer.

| N | Concentration Range* (ng/mL) | Slope | Slope 95% CI | Intercept | Intercept 95% CI | Correlation Coefficient R |
|-----|------------------------------|-------|--------------|-----------|------------------|---------------------------|
| 123 | 1.4 - 25 | 1.04 | 1.01 - 1.07 | 0.081 | -0.074 - 0.19 | 0.99 |

*Range is Access 2 values

Linearity: A verification study was performed to evaluate the linearity of the Access Folate assay on the Dxl 9000 Access Immunoassay Analyzer based on CLSI EP06-Ed2. The results of this study met the acceptance criterion, indicating that the Access Folate assay is linear on the Dxl 9000 Immunoassay Analyzer throughout the analytical measuring interval (2.0 - 24.8 ng/mL).

Serum Imprecision: Verification studies were performed to determine the imprecision of the Access Folate assay for serum samples on the Dxl 9000 Access Immunoassay Analyzer using a protocol based on CLSI EP-05-A3. The study was run on three Dxl 9000 Immunoassay analyzers, three reagent lots, and three calibrator lots. Five (5) serum samples, with varying Folate concentrations, were assayed in duplicate with two runs per day, over 20-22 days. The study met the minimum requirement of 80 replicates per sample on each instrument and reagent lot combination. The within-laboratory (total) % CV was between 2.2% and 4.4% for Folate concentrations > 2.0 ng/mL. The within-laboratory (total) SD was between 0.10 - 0.21 for Folate concentrations ≤ 2.0 nq/mL.

The repeatability (within-run) % CV was between 1.6% and 2.7% for Folate concentrations > 2.0 ng/mL. The repeatability (within-run) SD was between 0.08 -0.09 for Folate concentrations ≤ 2.0 ng/mL.

| Serum Folate<br>(ng/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 | 88 | 1.7 | 0.09 | N/A | 0.10 | N/A | 0.16 | N/A | 0.21 | N/A |
| Sample 2 | 88 | 4.7 | 0.10 | 2.1 | 0.07 | 1.4 | 0.17 | 3.6 | 0.21 | 4.4 |
| Sample 3 | 88 | 9.2 | 0.25 | 2.7 | 0.00 | 0.0 | 0.27 | 2.9 | 0.36 | 3.9 |
| Sample 4 | 88 | 16 | 0.3 | 2.0 | 0.2 | 1.2 | 0.4 | 2.7 | 0.6 | 3.6 |
| Sample 5 | 88 | 21 | 0.4 | 2.1 | 0.3 | 1.3 | 0.6 | 2.7 | 0.8 | 3.7 |

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RBC Imprecision: Verification studies were performed to determine the imprecision of the Access Folate assay for hemolysate samples on the Dxl 9000 Access Immunoassay Analyzer using a protocol based on CLSI EP-05-A3. The study was run on one Dxl 9000 Access Immunoassay Analyzer, one reagent lot, and one calibrator lot. Six whole blood hemolysate samples, with varying Folate concentrations, were tested in the study. The within-laboratory (total) % CV ranged from 1.9% to 4.9%.

| Hemolysate Folate<br>Concentration (ng/mL) | | Repeatability<br>(Within-run) | | Between-run | | Between-<br>day | | Within-<br>Laboratory | | |
|--------------------------------------------|----|-------------------------------|------|-------------|------|-----------------|------|-----------------------|------|-----|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 80 | 5.0 | 0.21 | 4.3 | 0.00 | 0.004 | 0.00 | 0.001 | 0.21 | 4.3 |
| Sample 2 | 80 | 11 | 0.3 | 2.8 | 0.3 | 2.8 | 0.0 | 0.02 | 0.5 | 4.0 |
| Sample 3 | 80 | 11 | 0.5 | 4.4 | 0.0 | 0.02 | 0.2 | 2.2 | 0.5 | 4.9 |
| Sample 4 | 80 | 13 | 0.2 | 1.9 | 0.1 | 0.5 | 0.0 | 0.002 | 0.3 | 1.9 |
| Sample 5 | 80 | 18 | 0.4 | 2.2 | 0.3 | 1.8 | 0.3 | 1.4 | 0.6 | 3.1 |
| Sample 6 | 80 | 22 | 0.4 | 1.8 | 0.3 | 1.2 | 0.0 | 0.003 | 0.5 | 2.1 |

LoB/LoD: Verification studies were performed to determine the Limit of Blank (LoB) and Limit of Detection (LoD) for the Access Folate assay on the Dxl 9000 Access Immunoassay Analyzer using a protocol based on CLSI EP17-A2. The assay is designed to meet the claimed LoB of 0.80 ng/mL (1.81 nmol/L), LoD of 1.0 ng/mL (2.27 nmol/L).

LoQ: Verification studies were performed to determine the Limit of Quantitation (LoQ) for the Access Folate assay on the Dxl 9000 Access Immunoassay Analyzer using a protocol based on CLSI EP17-A2. The LoQ for Access Folate is designed to meet the claimed LoQ of < 2.0 ng/mL (4.53 nmol/L) based on a 20% CV.

#### Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access Folate Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access Folate Assay on the Access 2 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.