The Access 25(OH) Vitamin D Total assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of total 25-hydroxyvitamin D [25(OH) vitamin D] levels in human serum and plasma using the DxI Access Immunoassay Analyzers. Results are to be used as an aid in the assessment of vitamin D sufficiency.

Device Description

The Access 25(OH) Vitamin D Total assay is a competitive binding immunoenzymatic assay. The Access 25(OH) Vitamin D Total assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access 25(OH) Vitamin D Total assay reagent pack, Access 25(OH) Vitamin D Total assay calibrators, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassav Analyzer in a clinical laboratory setting.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Access 25(OH) Vitamin D Total assay, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Target or Range)	Reported Device Performance (Access 25(OH) Vitamin D Total on Dxl 9000 Access)
Method Comparison: R²	≥ 0.90	0.97
Method Comparison: Slope	1.00 ± 0.10	1.05 (with 95% CI of 0.99 – 1.10)
Precision (Within-laboratory total % CV for > 15.0 ng/mL)	Not explicitly stated as acceptance criteria, but implied to be within acceptable clinical limits.	Ranged from 4.3% to 9.0%
Precision (Within-laboratory total SD for ≤ 15.0 ng/mL)	Not explicitly stated as acceptance criteria, but implied to be within acceptable clinical limits.	Ranged from 0.09 to 2.2
Linearity	Linear throughout the analytical measuring interval.	Linear throughout the analytical measuring interval of approximately 7.0-120 ng/mL.
Limit of Blank (LoB)	Not explicitly stated as acceptance criteria, but implied that the determined LoB should be low enough for clinical utility.	2.5 ng/mL
Limit of Detection (LoD)	Not explicitly stated as acceptance criteria, but implied that the determined LoD should be low enough for clinical utility.	4.5 ng/mL
Limit of Quantitation (LoQ)	≤ 20% within-lab CV	7.0 ng/mL (with ≤ 20% within-lab CV)

2. Sample Size Used for the Test Set and Data Provenance

Method Comparison: 150 serum samples. The provenance of these samples (country of origin, retrospective/prospective) is not specified in the provided text.
Precision: Multiple serum samples were tested in duplicate. The exact number of distinct serum samples beyond Sample 1-6 (which represent different concentration levels) is not specified, but each of the 6 samples was tested with N=80 replicates. The provenance is not specified.
Limit of Blank (LoB): 120 replicates of a zero-analyte sample. The provenance is not specified.
Limit of Detection (LoD): 8 to 11 serum samples containing low levels of Vitamin D analyte. These samples were tested over five days with one run per day and nine replicates per run for each pack lot, resulting in ≥ 40 replicates minimally required for LoD estimation for each sample on each pack lot tested. The provenance is not specified.
Limit of Quantitation (LoQ): 10-13 serum samples containing low levels of Vitamin D analyte. Samples were tested in replicates of nine per run with one run per day and five total days on each pack lot and instrument, resulting in a minimum of 40 replicates for each sample on each pack lot. The provenance is not specified.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This device is an in vitro diagnostic (IVD) assay for quantitative determination of a biomarker (25-hydroxyvitamin D). The ground truth for such assays is established through analytical methods and reference standards, not typically by human expert consensus or pathology review in the way a diagnostic imaging AI might be evaluated.

Therefore:

Number of experts: Not applicable.
Qualifications of experts: Not applicable.

The assay is traceable to NIST-Ghent ID-LC-MS/MS, which serves as a highly accurate reference method for establishing the true concentration of Vitamin D in samples.

4. Adjudication Method for the Test Set

Not applicable for this type of IVD assay. The performance is assessed by comparing results directly to reference methods or statistical metrics, not through expert adjudication of qualitative or semi-quantitative interpretations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is an automated in vitro diagnostic assay, not an AI-assisted diagnostic imaging tool that would involve human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies described (Method Comparison, Precision, Linearity, LoB, LoD, LoQ) evaluate the performance of the device (assay on the analyzer) in a standalone fashion, without human interpretation or intervention beyond running the tests according to protocol.

7. The Type of Ground Truth Used

Method Comparison: The predicate device (Access 25(OH) Vitamin D Total assay run on the Access 2 Immunoassay System, K142373) serves as the comparator or "reference" for this study. While not an absolute ground truth, it's the established method against which the new device on the new instrument is compared for substantial equivalence.
Precision, Linearity, LoB, LoD, LoQ: These studies rely on the inherent properties of the assay and statistical methodologies (e.g., CLSI guidelines) to characterize the device's analytical performance. The reference standard for traceability for the analyte itself is NIST-Ghent ID-LC-MS/MS. Low-level and zero-analyte samples are used to establish limits.

8. The Sample Size for the Training Set

This document describes the validation studies for a new IVD assay and instrument combination. It does not mention a "training set" in the context of machine learning, as this is a chemical immunoassay, not an AI/ML-based device. The term "training set" is not relevant here.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as there is no "training set" for this type of device.

Summary

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January 19, 2023

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

Re: K223503

Trade/Device Name: Access 25(OH) Vitamin D Total Regulation Number: 21 CFR 862.1825 Regulation Name: Vitamin D test system Regulatory Class: Class II Product Code: MRG Dated: November 21, 2022 Received: November 22, 2022

Dear Kate Oelberg:

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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Digitally signed by Paula____ Paula Caposino -S Caposino -S Date: 2023.01.19
15:31:11 -05'00'

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

Enclosure

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Indications for Use

510(k) Number (if known) K223503

Device Name Access 25(OH) Vitamin D Total

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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☒ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)
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510 (k) Summary

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.

510(k) Number K223503 Date Prepared: 01/19/2023

Submitter Name and Address:

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

Primary Contact:

Kate Oelberg, Senior Staff Quality and Regulatory Affairs Email: kmoelberg@beckman.com Phone: (612) 431-7315

Alternate Contact:

Kuljeet Kaur, Requlatory Affairs Manager Email: kkaur@beckman.com Office Phone: (952) 465-1914

Trade Name: Access 25(OH) Vitamin D Total Common Name: 25(OH) vitamin D Classification Regulation: 21 CFR 862.1825 Classification Product Code: MRG

Predicate Device:

Access 25(OH) Vitamin D Total 510(k) Number K142373

Device Description

Intended Use

The Access 25(OH) Vitamin D Total assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of total 25-hydroxyvitamin D [25(OH) vitamin D] levels in human serum and plasma using the Dxl Access Immunoassay Analyzers. Results are to be used as an aid in the assessment of vitamin D sufficiency.

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Comparison of Technological Characteristics to the Predicate (Assay)

SystemAttribute/Characteristic	Predicate Access 25(OH)Vitamin D Total assay(K142373) run on theAccess 2 ImmunoassaySystem	Access 25(OH) Vitamin DTotal assay run on the Dxl9000 Access ImmunoassayAnalyzer Instrument
Intended Use/ Indicationsfor Use	The Access 25(OH) Vitamin DTotal assay is a paramagneticparticle,chemiluminescentimmunoassay for thequantitative determination of total25-hydroxyvitamin D [25(OH)vitamin D] levels in human serumand plasma using theAccess 2 Immunoassay Systems.Results are to be used as an aidin the assessment of vitamin Dsufficiency.	The Access 25(OH) Vitamin DTotal assay is a paramagneticparticle,chemiluminescentimmunoassay for thequantitative determination of total25-hydroxyvitamin D [25(OH)vitamin D] levels in human serumand plasma using the Dxl AccessImmunoassay Analyzers. Resultsare to be used as an aid in theassessmentofvitaminDsufficiency.
Analyte Measured	25(OH) Vitamin D	Same
Traceable to	NIST-Ghent ID-LC-MS/MS	Same
Technology	Competitive Immunoassay	Same
Format	Chemiluminescent	Same
Method	Automated	Same
Calibration	Utilizes a stored calibration curve	Same
Sample Type	Serum/Li Hep Plasma	Same
Measuring Range	7.0-120 ng/mL (17.5 to 300nmol/L)	Same
Stability	28 days after opening	Same
Reagent Packformulation andpackaging	Access Reagent Pack formulationand packaging.	Same
Sample Volume	30uL	13uL
Instrument	Access 2 Immunoassay system	Dxl 9000 Access ImmunoassayAnalyzer
Substrate	Access Substrate	Lumi-Phos PRO substrate
Reagent Configurations	One Configuration:100 determinations, 2 packs, 50tests/pack	Two Configurations:1) 100 determinations, 2 packs, 50tests/pack (for predicate andcandidate instrument)2) 200 determinations, 2 packs,100 tests/pack (for candidateinstrument only)

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Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A3: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Third Edition

CLSI EP06-2nd Edition : Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline

CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline - Second Edition

CLSI EP09c-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples- Third Edition

Summary of Studies:

Method Comparison: A method comparison study was performed to compare the Access 25(OH) Vitamin D Total assay on the Dxl 9000 Access Immunoassay Analyzer to the predicate device. A total of one hundred fifty (150) serum samples falling within the measuring range of the Access 25(OH) Vitamin D Total assay were evaluated. The results of the within range method comparison study met the acceptance criteria of R2 ≥ 0.90 and slope 1.00 ± 0.10.

N	ConcentrationRange*(ng/mL)	Slope	Slope95% Cl	Intercept	Intercept95% Cl	R
150	7.0 - 120	1.05	0.99 –1.10	0.94	0.14 - 2.0	0.97

*Range is Access 2 values

Precison: A study based on CLSI EP05-A3 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple serum samples in duplicate in 2 runs per day for a minimum of 20 days. The within-laboratory (total) % CV ranged from 4.3% to 9.0%, for Vitamin D concentrations > 15.0 ng/mL. The within-laboratory (total) SD ranged from 0.09 to 2.2 for Vitamin D concentrations ≤ 15.0 ng/mL.

ng/mL		Repeatability(Within-Run)		Between-Run		Between-Day		Within-Laboratory
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	80	7.0	0.8	12.1	0.7	10.6	0.7	9.3	1.3	18.6
Sample 2	80	15.6	0.9	5.5	0.6	3.7	0.9	6.0	1.4	9.0
Sample 3	80	28	1.3	4.4	1.1	4.0	0.9	3.2	1.9	6.8
Sample 4	80	71	1.6	2.3	1.9	2.6	1.8	2.5	3.1	4.3
Sample 5	80	95	2.4	2.5	2.3	2.4	2.8	3.0	4.3	4.5
Sample 6	80	111	3.1	2.8	3.2	2.9	2.1	1.9	4.9	4.5

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Linearity: A verification study was performed to evaluate the linearity of the Access 25(OH) Vitamin D Total assay on the Dxl 9000 Access Immunoassay Analyzer based on CLSI EP06-Ed2. The Access 25(OH) Vitamin D Total assay is linear on the Dxl 9000 Access Immunoassay Analyzer throughout the analytical measuring interval of approximately 7.0-120 ng/mL

Limit of Blank (LoB): In one study, LoB was tested using a protocol based on CLSI EP17-A2. A total of 120 replicates of a zero analyte sample (Access 25(OH) Vitamin D Total Calibrator SQ) were measured using multiple reagent packs on multiple Dxl 9000 Access Immunoassay Analyzers. The LoB for Access 25(OH) Vitamin D Total assay is 2.5 ng/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Detection (LoD): In one study, LoD was tested using a protocol based on CLSI EP17-A2. Three Dxl 9000 Access Immunoassay Analyzers were used in the study design with three reagent lots and one calibrator lot. Eight to eleven serum samples containing low levels of Vitamin D analyte were prepared. Samples were tested over five days with one run per day and nine replicates per run for each pack lot. This resulted in ≥ 40 replicates minimally required for LoD estimation for each sample on each pack lot tested. The LoD estimate for the Access 25(OH) Vitamin D Total assay is 4.5 ng/mL on Dxl 9000 Access Immunoassay Analyzer.

Limit of Quantitation (LoQ): In one study, LoQ was tested using a protocol based on CLSI EP17-A2. For estimation of LoQ, 10-13 serum samples containing low levels of Vitamin D analyte were measured. Samples were tested in replicates of nine per run with one run per day and five total days on each pack lot and instrument. A minimum of 40 replicates for each sample on each pack lot was tested. The maximum LoQ (≤ 20% within-lab CV) determined for the Access 25(OH) Vitamin D Total assay is 7.0 ng/mL on Dxl 9000 Access Immunoassay Analyzer.

Other claims: The claims for the analytical specificity, reference intervals, matrix comparison are being transferred from file K142373.

Substantial Equivalence Comparison Conclusion

Beckman Coulter's Access 25(OH) Vitamin D Total assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to Access 25(OH) Vitamin D Total assay on the Access 2 Immunoassay System (K142373) 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.

Regulation Number and Section

§ 862.1825 Vitamin D test system.

(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.