The Access Ostase assay is a paramagnetic particle, chemiluminescent immunoassay for use with the Access Immunoassay Systems for the quantitative measurement of bone alkaline phosphatase (BAP), an indicator of osteoblastic activity, in human serum and plasma. This device is intended to be used as an aid in the management of postmenopausal osteoporosis and Paget's disease.

Device Description

The Access Ostase assay is a one-step sandwich immunoenzymatic assay. The Access Ostase assay consists of the reagent pack, calibrators and QCs. Other items needed to run the assay include substrate and wash buffer. The Access Ostase assay reagent pack, Access Ostase assay calibrators, Access Ostase QCs, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.

AI/ML Overview

The provided text describes the performance of the Beckman Coulter Access Ostase assay on the Dxl 9000 Access Immunoassay Analyzer, comparing it to the predicate device (Access Ostase on Access 2 Immunoassay System).

Here's an analysis of the acceptance criteria and the studies performed, structured as requested:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for each performance characteristic in a separate, clear table format. However, it does outline the assay's design goals for imprecision and then presents the results. For other parameters like linearity and detection limits, it states the claimed values or that linearity was demonstrated. I will infer the acceptance criteria for imprecision from the "designed to have" statement and present the reported performance.

Parameter	Acceptance Criteria	Reported Device Performance (Access Ostase on Dxl 9000)
Method Comparison	Implicit: Close statistical agreement (slope near 1, intercept near 0, high correlation) with the predicate device (Access Ostase on Access 2 Immunoassay System). While not explicitly stated as an "acceptance criteria," the results indicate substantial equivalence.	N: 163 samples Concentration Range: 0.34 - 108 µg/L Slope: 0.95 (95% CI: 0.93 - 0.98) Intercept: 0.53 (95% CI: 0.32 - 0.75) Correlation Coefficient (R): 1.00
Imprecision	≤ 0.2 µg/L SD at concentrations ≤ 3 µg/L ≤ 7.0% CV at concentrations > 3 µg/L (within-laboratory imprecision)	Sample 1 (Mean 1.8 µg/L): SD 0.1, %CV 4.7 Sample 2 (Mean 9.1 µg/L): SD 0.4, %CV 4.1 Sample 3 (Mean 25 µg/L): SD 1.1, %CV 4.4 Sample 4 (Mean 38 µg/L): SD 1.6, %CV 4.3 Sample 5 (Mean 98 µg/L): SD 4.1, %CV 4.2 All reported within-laboratory %CVs are ≤ 7.0% and the SD for Sample 1 (1.8 µg/L) is 0.1 µg/L, meeting the criteria.
Linearity	Implicit: Demonstrate linearity across the measuring interval.	Demonstrated linearity across the measuring interval.
Limit of Blank (LoB)	Claimed LoB of 0.1 µg/L.	Claimed LoB for Access Ostase assay is 0.1 µg/L on Dxl 9000 Access Immunoassay Analyzer.
Limit of Detection (LoD)	Claimed LoD of 0.1 µg/L.	Claimed LoD for Access Ostase assay is 0.1 µg/L on Dxl 9000 Access Immunoassay Analyzer.
Limit of Quantitation (LoQ)	Claimed LoQ of 0.3 µg/L.	Claimed LoQ for Access Ostase assay is 0.3 µg/L on Dxl 9000 Access Immunoassay Analyzer.

2. Sample size used for the test set and the data provenance:

Method Comparison Test Set:
- Sample Size: 163
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the study involved comparing results from two different immunoassay systems (Access 2 and Dxl 9000) using patient samples, implying real-world or simulated clinical samples.
Imprecision Test Set:
- Sample Size: 80 for each of the 5 samples tested (total of 400 individual measurements of samples).
- Data Provenance: Not explicitly stated. The study involved testing "multiple samples in duplicate in 2 runs per day for a minimum of 20 days," which suggests a controlled laboratory setting.
Linearity, LoB, LoD, LoQ: The sample sizes for these studies are not explicitly mentioned, nor is their specific provenance beyond being performed "on the Dxl 9000 Access Immunoassay Analyzer."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This information is not applicable to an in vitro diagnostic (IVD) assay that measures quantitative analytes like bone alkaline phosphatase. The "ground truth" for such devices is typically established through reference methods, certified reference materials, or statistical comparison to a legally marketed predicate device (as done here). There are no "experts" in the human perception or diagnostic interpretation sense used to establish ground truth for this type of test.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

Not applicable. Adjudication methods like 2+1 or 3+1 are typically used in studies involving human interpretation (e.g., radiology reads) where discrepancies between experts need to be resolved to establish ground truth. This is a quantitative immunoassay.

5. 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 device is an in vitro diagnostic immunoassay, not an AI-assisted diagnostic tool for human readers. No MRMC study was performed.

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

This device is an automated immunoassay system that provides quantitative results. The performance studies described (Method Comparison, Imprecision, Linearity, LoB/LoD/LoQ) inherently represent the standalone performance of the device (including its reagents and analyzer software) in generating these quantitative results. It operates without direct human-in-the-loop interpretation of the primary measurement signal for the reported value. A human reviews the final numerical result, but the device itself generates that result primarily through an automated process.

7. The type of ground truth used:

Method Comparison: The ground truth was established by comparison to the predicate device (Access Ostase on Access 2 Immunoassay System). This assumes the predicate device's measurements represent a valid "truth" for substantial equivalence purposes. Patient samples were used, and their values from one system were compared to the other.
Imprecision: The ground truth for evaluating imprecision is the inherent variability of the measurement process itself, determined by repeated measurements of samples with known (or established) concentrations.
Linearity, LoB, LoD, LoQ: These are determined using samples of known concentrations (dilutions, blank samples, low-concentration samples) and statistical methods based on CLSI guidelines.

8. The sample size for the training set:

Not applicable. This device is a quantitative immunoassay system, not a machine learning or AI model that requires a "training set" in the conventional sense. The development of such assays involves extensive research, development, and optimization of reagents and protocols, but this is distinct from "training data" for an algorithm.

9. How the ground truth for the training set was established:

Not applicable, as there is no "training set" in the context of an AI/ML algorithm.

Summary

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April 15, 2024

Beckman Coulter, Inc. Kate Oelberg Senior Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318

Re: K232904

Trade/Device Name: Access Ostase Regulation Number: 21 CFR 862.1050 Regulation Name: Alkaline Phosphatase or Isoenzymes Test System Regulatory Class: Class II Product Code: CIN Dated: March 1, 2024 Received: March 1, 2024

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Digitally signed by Thomas C. Thomas C. Miller -S Date: 2024.04.15 Miller -S 15:56:59 -04'00'

for 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

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Indications for Use

510(k) Number (if known) K232904

Device Name Access Ostase

Indications for Use (Describe)

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)

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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 K232904

Submitted Bv:

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

Primarv Contact:

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

Alternate Contact:

Madhuri Boppana Regulatory Affairs Analyst, Senior Email: mboppana@beckman.com

Device Name

Common Name: Access Ostase Trade Name: Access Ostase Classification Name: Alkaline phosphatase or isoenzymes test system. Classification Regulation: [21 CFR 862.1050] Product Code: CIN

Predicate Device Device Name: Access Ostase 510(k) Numbers: K994278

Device Description

Intended Use

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Parameter	Access Ostase on Access 2Immunoassay System (Predicate)	Access Ostase on Dxl9000 AccessImmunoassay System
Intended use	The Access Ostase assay is aparamagnetic particle, chemiluminescentimmunoassay for use with the AccessImmunoassay Systems for thequantitative measurement of bonealkaline phosphatase (BAP), an indicatorof osteoblastic activity, in human serumand plasma. This device is intended tobe used as an aid in the management ofpostmenopausal osteoporosis andPaget's disease.	Same
AnalyteMeasured	Bone alkaline phosphatase (BAP), anindicator of osteoblastic activity, inhuman serum and plasma	Same
Technology	One-step immunoenzymatic assay	Same
Format	Chemiluminescent	Same
Method	Automated	Same
Calibration	Utilizes a stored calibration curve	Same
Sample Type	Serum or plasma	Same
MeasuringRange	Approximately 0.1 – 120 μg/L	Approximately 0.3 – 120μg/L
Instrument	Access Immunoassay system	Dxl 9000 AccessImmunoassay Analyzer
Substrate	Access Substrate	Lumi-Phos Pro Substrate

Comparison of Technological Characteristics to the Predicate

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

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

Summary of Studies

Method Comparison: A study based on CLSI EP09c, 3rd Edition using Passing Bablok regression and Pearson's correlation compared the Access 2 Immunoassay System and the Dxl 9000 Access Immunoassay Analyzer.

N	ConcentrationRange*(µg/L)	Slope	Slope95% CI	Intercept	Intercept95% CI	CorrelationCoefficientR
163	0.34 - 108	0.95	0.93 - 0.98	0.53	0.32 - 0.75	1.00

*Range is Access 2 values

Imprecision: The assay was designed to have within-laboratory imprecision as listed below:

• ≤ 0.2 µg/L SD at concentrations ≤ 3 µg/L

• ≤ 7.0% CV at concentrations > 3 µg/L

A study based on CLSI EP05-A3 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple samples in duplicate in 2 runs per day for a minimum of 20 days.

Concentration (µg/L)		Repeatability(Within-Run)		Between-Run		Between-Day		Within-Laboratory
Sample	N	Mean	SD	%CV	SD	%CV	SD	%CV	SD	%CV
Sample 1	80	1.8	0.1	4.6	0.01	0.8	0.0001	0.0	0.1	4.7
Sample 2	80	9.1	0.3	3.3	0.2	2.0	0.2	1.7	0.4	4.1
Sample 3	80	25	0.8	3.3	0.6	2.3	0.5	1.8	1.1	4.4
Sample 4	80	38	1.4	3.6	0.8	2.1	0.4	1.0	1.6	4.3
Sample 5	80	98	3.2	3.3	2.3	2.4	0.9	0.9	4.1	4.2

Linearity: A study based on CLSI EP06-Ed2 performed on the Dxl 9000 Access Immunoassay Analyzer determined the assay demonstrated linearity across the measuring interval.

Limit of Blank (LoB): The claimed LoB for Access Ostase assay is 0.1 ug/L on Dxl 9000 Access Immunoassay Analyzer.

Limit of Detection (LoD): The claimed LoD for Access Ostase assay is 0.1 µg/L on Dxl 9000 Access Immunoassay Analyzer.

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Limit of Quantitation (LoQ): The claimed LoQ for Access Ostase assay is 0.3 µg/L on Dxl 9000 Access Immunoassay Analyzer.

Substantial Equivalence Comparison Conclusion

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

Regulation Number and Section

§ 862.1050 Alkaline phosphatase or isoenzymes test system.

(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.