(88 days)
The Access Myoglobin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of myoglobin levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis of heart or renal disease.
The Access Myoglobin assay is a sandwich immunoenzymatic assay. The Access Myoglobin assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access Myoglobin assay reagent pack, Access Myoglobin assay calibrators, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.
The provided text describes the Beckman Coulter Access Myoglobin assay, which is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of myoglobin levels in human serum and plasma. The K231832 submission seeks to demonstrate substantial equivalence to the predicate device (Access Myoglobin assay, K021229) when run on the Dxl 9000 Access Immunoassay Analyzer.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a separate section with pass/fail thresholds for all performance metrics. However, it presents the results of various performance studies against industry guidelines (CLSI standards), which implicitly serve as the acceptance criteria for demonstrating appropriate performance.
| Performance Characteristic | Acceptance Criteria (Implicit from CLSI guidelines and typical assay requirements) | Reported Device Performance (Access Myoglobin on Dxl 9000) |
|---|---|---|
| Method Comparison (vs. Predicate) | Slope near 1.0, Intercept near 0, High correlation (R) | Slope: 0.99, Intercept: 0.47, R: 1.00 |
| Imprecision | ≤ 1.10 ng/mL SD at concentrations ≤ 11.0 ng/mL; ≤ 10.0% CV at concentrations > 11.0 ng/mL | Repeatability (Within-Run): 2.0-2.3% CV, 0.18 SD (low) |
| Between-Run: 2.2-4.0% CV, 0.18-85.9 SD | ||
| Between-Day: 0.0-3.0% CV, 0.0-3.0 SD | ||
| Within-Laboratory: 3.7-5.4% CV, 0.31-101.9 SD | ||
| Linearity | Demonstrate linearity across the measuring interval (e.g., polynomial fit not significantly better than linear) | Demonstrated linearity across the measuring interval |
| Limit of Blank (LoB) | Establish a LoB that is analytically sound | 3.0 ng/mL (μg/L) |
| Limit of Detection (LoD) | Establish a LoD that is analytically sound | 3.0 ng/mL (μg/L) |
| Limit of Quantitation (LoQ) | Establish a LoQ with acceptable imprecision (e.g., ≤ 20% within-lab CV) | 3.0 ng/mL (μg/L) at ≤ 20% within-lab CV |
2. Sample Sizes Used for the Test Set and Data Provenance
- Method Comparison: N = 155 (This refers to 155 patient samples). The data provenance (country of origin, retrospective/prospective) is not specified in the provided text.
- Imprecision: N = 80 per sample assessed (e.g., Sample 1, Sample 2, etc.), which involved multiple samples tested in duplicate in 2 runs per day for a minimum of 20 days.
- Linearity: Sample size not explicitly stated, but typically involves a series of diluted/spiked samples.
- LoB, LoD, LoQ: Not explicitly stated as a single "sample size" but involved multiple reagent lots and 3 instruments over a minimum of 3-5 days.
The data provenance for all studies (country of origin, retrospective or prospective) is not specified in the provided document.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The Access Myoglobin assay is an in vitro diagnostic device for quantitative measurement of a biomarker. Its "ground truth" is established through analytical performance studies, not typically by expert review of individual cases as would be done for imaging or clinical decision support AI. Therefore, this section is not applicable in the traditional sense for this type of device. The "truth" is based on the accurate measurement of myoglobin concentration.
4. Adjudication Method for the Test Set
As this is an in vitro diagnostic quantitative assay, there is no adjudication method described or necessary in the context of expert consensus, as might be found for imaging AI. The performance is assessed against reference methods or calibrated controls.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the Effect Size
No MRMC comparative effectiveness study was done. This type of study is relevant for imaging or clinical decision support AI where human readers interpret results, and the AI might augment their performance. For a quantitative immunoassay, the "reader" is effectively the instrument, and the performance is evaluated on its analytical accuracy and precision.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented (Method Comparison, Imprecision, Linearity, LoB/LoD/LoQ) demonstrate the standalone performance of the Access Myoglobin assay on the Dxl 9000 Access Immunoassay Analyzer. These are analytical performance studies of the device itself, without human interpretation as a primary variable.
7. The Type of Ground Truth Used
The ground truth for these analytical performance studies is based on:
- Reference measurements: For method comparison, the predicate device (Access 2 Immunoassay System) served as the reference standard.
- Established concentrations/materials: For imprecision, linearity, LoB/LoD/LoQ, the ground truth is based on known concentrations of myoglobin in controls, calibrators, and spiked samples, prepared according to industry standards.
- Analytical principles: The assay measures myoglobin concentration, and the "ground truth" is the actual quantity of myoglobin present in a sample, determined through scientifically validated methods.
8. The Sample Size for the Training Set
This information is not provided in the document. For an immunoassay like this, there isn't a "training set" in the machine learning sense. The device's operational parameters and assay design are developed through extensive research and development, but this is distinct from an AI training dataset.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit "training set" in the AI sense for this immunoassay submission, this question is not directly applicable. The "ground truth" during the development and optimization of such an assay would involve internal analytical studies using characterized materials and reference methods to ensure the assay accurately measures myoglobin concentrations.
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September 18, 2023
Beckman Coulter, Inc. Kate Oelberg Senior Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318
Re: K231832
Trade/Device Name: Access Myoglobin Regulation Number: 21 CFR 866.5680 Regulation Name: Myoglobin Immunological Test System Regulatory Class: Class II Product Code: DDR Dated: June 21, 2023 Received: June 22, 2023
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 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,
Paula V. Caposino -S
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) K231832
Device Name Access Myoglobin
Indications for Use (Describe)
The Access Myoglobin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of myoglobin levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis of heart or renal disease.
| 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 K231832
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 Myoglobin Common Name: Myoqlobin Classification Regulation: 21 CFR 866.5680 Classification Product Code: DDR
Predicate Device:
Access Myoglobin 510(k) Number K021229
Device Description
The Access Myoglobin assay is a sandwich immunoenzymatic assay. The Access Myoglobin assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffer. The Access Myoqlobin assay reagent pack, Access Myoqlobin assay calibrators, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.
Intended Use
The Access Myodobin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of myoglobin levels in human serum and plasma using the Access Immunoassay Systems to aid in the diagnosis of heart or renal disease.
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Comparison of Technological Characteristics to the Predicate (Assay)
| SystemAttribute/Characteristic | Predicate Access Myoglobinassay (K021229) run on theAccess 2 ImmunoassaySystem | Access Myoglobin assay runon the Dxl 9000 AccessImmunoassay AnalyzerInstrument |
|---|---|---|
| Intended Use/Indications for Use | The Access Myoglobin assayis a paramagnetic particle,chemiluminescentimmunoassay for thequantitativedetermination of myoglobinlevels in human serum andplasma using the AccessImmunoassay Systems. | Same |
| Assay Principles | The Access Myoglobin assayis a two-site immunoenzymatic("sandwich") assay. A sampleis added to a reaction vesselwith mouse monoclonal anti-myoglobin-alkalinephosphatase conjugate,mouse monoclonal anti-myoglobin-biotinconjugate, and paramagneticparticles coated with goat anti-biotin. | Same |
| Solid Support | Paramagnetic Particles | Same |
| Detection System | Utilizes dioxetane-basedchemiluminescent substrate;Measures light production froma chemiluminescent reaction | Same |
| Calibrators | Liquid calibrators preparedfrom buffered bovine proteinmatrix and human skeletalMyoglobin at various levels | Same |
| Sample Type | Serum/Plasma (heparin orEDTA) | Same |
| Measuring Range | 1 - 4000 ng/mL | 3.0 - 4000 ng/mL |
| Expected Results | Separate ranges for Heparinplasma/serum vs EDTAplasma | Same ranges |
| Instrument | Access Immunoassay system | Dxl 9000 AccessImmunoassay Analyzer |
| Substrate | Access Substrate | Lumi-Phos PRO substrate |
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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: Measurement Procedure Comparison and Bias Estimation Using Patient Samples-Third Edition
CLSI EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory - Third Edition
CLSI EP35 Assessment of Equivalence of Suitability of Specimen Types for Medical Laboratory Measurement Procedures - First Edition
Summary of Studies:
Method Comparison:_A study based on CLSI EP09c, 3rd Edition using Weighted Deming regression and Pearson's correlation compared the Access 2 Immunoassay System and the Dxl 9000 Access Immunoassay Analyzer.
| N | Concentration Range*(ng/mL) | Slope | Slope95% CI | Intercept | Intercept95% CI | R |
|---|---|---|---|---|---|---|
| 155 | 8.2 – 3900 | 0.99 | 0.98 – 1.00 | 0.47 | -0.10 – 1.0 | 1.00 |
*Range is Access 2 values
Imprecison: The assay was designed to have within-laboratory imprecision as listed below:
≤ 1.10 ng/mL (µg/L) SD at concentrations ≤ 11.0 ng/mL (µg/L)
≤ 10.0% CV at concentrations > 11.0 ng/mL (uq/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.
| ng/mL (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 | 7.9 | 0.18 | 2.3 | 0.18 | 2.2 | 0.17 | 2.2 | 0.31 | 3.9 |
| Sample 2 | 80 | 101 | 2.2 | 2.1 | 4.0 | 4.0 | 3.0 | 3.0 | 5.5 | 5.4 |
| Sample 3 | 80 | 465 | 8.0 | 1.7 | 15.1 | 3.2 | 0.0 | 0.0 | 17.0 | 3.7 |
| Sample 4 | 80 | 1763 | 35.0 | 2.0 | 57.5 | 3.3 | 0.1 | 0.0 | 67.3 | 3.8 |
| Sample 5 | 80 | 2719 | 54.8 | 2.0 | 85.9 | 3.2 | 0.0 | 0.0 | 101.9 | 3.7 |
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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), Limit of Detection (LoD) and Limit of Quantitation (LoQ): Limit of Blank (LoB), Limit of Detection (LoD), and Limit of Quantitation (LoQ) studies were conducted on the Dxl 9000 Access Immunoassay Analyzer following CLSI guideline EP17-A2 The LoB study included multiple reagent lots and 3 instruments over a minimum of 3 days. The LoD and LoQ studies included multiple reagent lots and 3 instruments over a minimum of 5 days.
| ng/mL (μg/L) | |
|---|---|
| Limit of Blank (LoB) | 3.0 |
| Limit of Detection (LoD) | 3.0 |
| Limit of Quantitation (LoQ)≤ 20% within-lab CV | 3.0 |
Substantial Equivalence Comparison Conclusion
Beckman Coulter's Access Myoglobin assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to Myoglobin assay on the Access Immunoassay System (K021229) 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.
§ 866.5680 Myoglobin immunological test system.
(a)
Identification. A myoglobin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the myoglobin (an oxygen storage protein found in muscle) in serum and other body fluids. Measurement of myoglobin aids in the rapid diagnosis of heart or renal disease.(b)
Classification. Class II (performance standards).