(59 days)
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.
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.
The provided document is a 510(k) Premarket Notification from the FDA for a diagnostic device, the "Access Vitamin B12" assay, manufactured by Beckman Coulter, Inc. It details the device's technical characteristics, its intended use, a comparison to a predicate device, and summaries of performance studies.
Here's the breakdown of the acceptance criteria and study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes the acceptance criteria and observed performance for several analytical studies conducted to demonstrate substantial equivalence of the new Access Vitamin B12 assay on the Dxl 9000 Access Immunoassay Analyzer to the predicate device.
| Performance Characteristic | Acceptance Criteria | Reported Device Performance | Met Criteria? |
|---|---|---|---|
| Method Comparison | R$^2 \ge 0.90$ | R$^2 = 0.97$ | Yes |
| Slope of 1.00 $\pm$ 0.14 | Slope = 1.00 (95% CI: 0.96 - 1.02) | Yes | |
| Intercept (No explicit criterion, but 0 is ideal) | Intercept = 6.1 (95% CI: -0.16 - 15) | Yes (Implied) | |
| Imprecision | SD $\le 12$ pg/mL for values $\le 100$ pg/mL | Observed total SD between 6 – 9 for samples $\le 100$ pg/mL | Yes |
| CV $\le 12.0$ % for values $> 100$ pg/mL | Observed total %CV between 2.7% and 7.7% for samples $> 100$ pg/mL | Yes | |
| Linearity | (Implicitly: demonstrate linearity throughout AMR) | Met the acceptance criterion; linear throughout 68 - 1,500 pg/mL | Yes |
| Limit of Detection (LoD) | LoD $\le 68$ pg/mL (50 pmol/L) | Observed LoD = 49 pg/mL (36 pmol/L) | Yes |
| Limit of Blank (LoB) | (Implicitly: demonstrate LoB value) | Claimed LoB = 50 pg/mL (37 pmol/L); Estimated LoB = 35 pg/mL (26 pmol/L) | Yes (Estimated LoB is lower than claimed) |
| Limit of Quantitation (LoQ) | LoQ $\le 68$ pg/mL (50 pmol/L) | Estimated LoQ (20% CV) = 42 pg/mL; Maximum observed LoQ = 68 pg/mL; Reported LoQ as 49 pg/mL (following CLSI EP17-A2 recommendation that LoQ $\ge$ LoD) | Yes |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison: N = 122 samples.
- Imprecision: 6 serum samples with varying Vitamin B12 concentrations were assayed. Each sample was assayed in duplicate, twice per day, over 21 days (resulting in 84 replicates per sample, 6 samples x 84 replicates = 504 total assays for imprecision).
- Linearity, LoB, LoD, LoQ: Specific sample sizes for these studies are not explicitly stated as 'N' values in the text, but the studies were performed (e.g., "verification studies") following CLSI protocols.
- Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given it's a clinical laboratory device study for regulatory submission, they are typically prospective analytical validation studies conducted in a controlled lab environment.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
N/A. This device is a quantitative diagnostic assay (Vitamin B12 levels) rather than an AI/ML-based image analysis or pattern recognition device that would typically rely on expert human consensus for ground truth. The "ground truth" for these analytical performance studies is established by the reference methods (predicate device measurements, defined concentrations for linearity/imprecision, and analytical standards for LoB/LoD/LoQ).
4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set
N/A. Adjudication methods are not applicable here since the "ground truth" is determined by established analytical measurements and reference values, not by human interpretation requiring consensus.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
N/A. MRMC studies are typically performed for imaging devices or AI-assisted diagnostic tools where human readers interpret cases, and the AI's impact on reader performance is assessed. This is a standalone in-vitro diagnostic (IVD) assay designed to provide quantitative results, not assist human readers in interpreting complex cases. The study effectively compares the new instrument (Dxl 9000) to the predicate instrument (Access Immunoassay System), not human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
While the term "standalone" is often used in the context of AI algorithms, this device functions as a standalone quantitative diagnostic assay. The performance studies (Method Comparison, Imprecision, Linearity, LoB/LoD/LoQ) demonstrate the analytical performance of the device itself (the "algorithm" being the assay chemistry and instrument processing) without human intervention in the result determination. The results are quantitative outputs (pg/mL or pmol/L of Vitamin B12).
7. The Type of Ground Truth Used
The ground truth for the analytical performance studies was established through:
- Method Comparison: Comparison against the predicate Access Vitamin B12 assay run on the Access Immunoassay System.
- Imprecision: Known or consistent concentrations of Vitamin B12 samples measured repeatedly.
- Linearity: Serially diluted samples or samples prepared with known, varied concentrations.
- LoB/LoD/LoQ: Use of blank samples, low-concentration samples, and statistical methods (CLSI EP17-A2 protocol) to determine limits.
Overall, the ground truth relies on analytical reference methods, known sample concentrations, and statistical methods as per industry best practices (CLSI guidelines) for IVD devices.
8. The Sample Size for the Training Set
N/A. This is a specific analytical test kit (immunoassay) that functions based on established biochemical principles, not a machine learning algorithm that requires a "training set" in the conventional sense of AI. Its performance is inherent to its design and chemical reagents, validated through the analytical performance studies described.
9. How the Ground Truth for the Training Set Was Established
N/A. As stated above, this device does not utilize a training set in the AI sense. Its "ground truth" for development and validation are based on chemical and analytical principles and reference standards.
{0}------------------------------------------------
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
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
{1}------------------------------------------------
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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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
{2}------------------------------------------------
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) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
{3}------------------------------------------------
Image /page/3/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red oval shape with two white curved lines inside, next to the company name "BECKMAN COULTER" in black, bold, sans-serif font. The company name is stacked, with "BECKMAN" on top of "COULTER".
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: (952)-465-1914 Email: kkaur@beckman.com
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: mboppana@beckman.com
{4}------------------------------------------------
| SystemAttribute/Characteristic | Predicate Access Vitamin B12 onAccess Immunoassay System | Access Vitamin B12 on Dxl 9000Access Immunoassay Analyzer |
|---|---|---|
| Analyte Measured | Access Vitamin B12 | Same |
| Standardization | USP Reference Material | Same |
| Intended Use/ Indicationsfor Use | The Access Vitamin B12 assay is aparamagnetic particle, chemiluminescentimmunoassay for the quantitativedetermination of vitamin B12 levels inhuman serum and plasma (heparin) usingthe Access Immunoassay Systems. | Same |
| Solid Phase | Paramagnetic particles coated with goatanti-mouse IgG; mouse monoclonal anti-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 formulationand packaging | Access Reagent Pack formulation andpackaging. | Same |
| Stability | Stable at 2 to 10°C for 14 days after initialuse | 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 - 1,107pmol/L) |
| Instrument | Access Immunoassay System | Dxl 9000 Access ImmunoassayAnalyzer |
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 | ConcentrationRange*(pg/mL) | Slope | Slope95% CI | Intercept | Intercept95% CI | CorrelationCoefficientR2 |
|---|---|---|---|---|---|---|
| 122 | 70 - 1248 | 1.00 | 0.96 - 1.02 | 6.1 | -0.16 - 15 | 0.97 |
*Range is Access values
{5}------------------------------------------------
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(Within-Run) | Between-Run | Between-Day | Within-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).
{6}------------------------------------------------
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.
§ 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.