(85 days)
Access Thyroglobulin assay is a paramagetic particle, chemiluminescent immunossay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.
The Access Thyroglobulin assay consists of the reagent pack and calibrators. Other items needed to run the assay include the Access Thyroglobulin Sample Diluent, substrate and wash buffer. The Access Tg assay along with the Access wash buffer and substrate are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.
Lumi-Phos PRO substrate was used with this pack. The modification does not affect the indications of the device or alter the fundamental scientific technology of the device.
The provided text is a 510(k) summary for the Access Thyroglobulin assay, which is a diagnostic device and not an AI/ML device. Therefore, many of the requested categories related to AI/ML device studies, such as "Number of experts used to establish the ground truth," "Adjudication method," "MRMC comparative effectiveness study," and "sample size for the training set," are not applicable.
However, I can extract the relevant information regarding acceptance criteria and study results for this diagnostic device.
Acceptance Criteria and Reported Device Performance for Access Thyroglobulin Assay (K240927)
1. Table of Acceptance Criteria and the Reported Device Performance
| Performance Metric | Acceptance Criteria (Implicit from reported results and CLSI guidelines) | Reported Device Performance (Access Thyroglobulin on Dxl 9000) |
|---|---|---|
| Method Comparison | Slope of 1.00 (95% CI covering 1.00); Intercept of 0.00 (95% CI covering 0.00); High Correlation Coefficient (R close to 1.00) | Slope: 1.00 (0.99 - 1.00); Intercept: 0.0044 (-0.029 - 0.021); Correlation Coefficient R: 1.00 |
| Imprecision (Within-lab/Total) | CV ≤ 10.0% at concentrations > 1.0 ng/mL; SD ≤ 0.1 ng/mL at concentrations ≤ 1.0 ng/mL | Achieved across all tested concentrations (e.g., 8.4% at 0.30 ng/mL, 6.8% at 5.5 ng/mL, 6.3% at 22 ng/mL, 2.5% at 111 ng/mL, 3.6% at 376 ng/mL, 3.6% at 417 ng/mL) |
| Reproducibility | Not explicitly stated as a separate acceptance criterion, but results imply meeting acceptable reproducibility for clinical use. | Example: Within-run CV 5.9% (0.34 ng/mL), Reproducibility CV 7.4% (0.34 ng/mL); Within-run CV 2.5% (402 ng/mL), Reproducibility CV 5.9% (402 ng/mL) |
| Linearity | Assay demonstrates linearity across the measuring interval. | Demonstrated linearity across the measuring interval. |
| Limit of Blank (LoB) | Not explicitly stated as a numerical criterion, but a low value is expected for accurate detection. | 0.03 ng/mL |
| Limit of Detection (LoD) | Not explicitly stated as a numerical criterion, but a low value is expected for accurate detection. | 0.05 ng/mL |
| Limit of Quantitation (LoQ) ≤20% within-lab CV | ≤ 0.1 ng/mL at 20% within-lab CV (explicitly stated criteria) | 0.1 ng/mL |
2. Sample sizes used for the test set and the data provenance
- Method Comparison: N = 187 samples. Data provenance is not specified (e.g., country of origin, retrospective/prospective).
- Imprecision: For each sample, N = 88 or 80. Data provenance is not specified.
- Reproducibility: For each sample, N = 75. Data provenance is not specified.
- Linearity, LoB, LoD, LoQ: Sample sizes for specific points within the linearity study or number of samples for LoB/LoD/LoQ determinations are not explicitly given, but the studies were conducted using "multiple samples," "multiple reagent lots," and "multiple days." Data provenance is not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This is a quantitative immunoassay for measuring thyroglobulin levels. The 'ground truth' for such a device is established by the analytical reference measurement procedures using a reference method or known concentrations, rather than expert consensus on diagnostic images or clinical assessments. Therefore, this question is not applicable in the context of this device.
4. Adjudication method for the test set
Not applicable for a quantitative immunoassay. The comparison is statistical analysis of measured values against a predicate device or expected values from reference materials.
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 is not an AI/ML device involving human readers or interpretation.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
The device is an automated immunoassay system. The performance studies ("Method Comparison," "Imprecision," "Reproducibility," "Linearity," "Detection Capability") represent the standalone performance of the assay and instrument without human interpretation of raw signals influencing the final quantitative result.
7. The type of ground truth used
For this immunoassay device, the "ground truth" implicitly refers to:
- Reference measurements from the predicate device (Access 2 Immunoassay System): Used for the method comparison study.
- Known concentrations/reference materials: Used to assess imprecision, linearity, and detection capabilities (LoB, LoD, LoQ) against expected values.
8. The sample size for the training set
Not applicable. This is a traditional diagnostic device, not an AI/ML device that requires a training set.
9. How the ground truth for the training set was established
Not applicable, as there is no training set for this type of device.
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June 28, 2024
Beckman Coulter, Inc. Muhammad Sheikh Staff Regulatory Affairs Beckman Coulter Inc 1000 Lake Hazeltine Drive Chaska, Minnesota 55318
Re: K240927
Trade/Device Name: Access Thyroglobulin Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: MSW Dated: April 4, 2024 Received: April 4, 2024
Dear Muhammad Sheikh:
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"
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(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).
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 OS 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.
Ying Mao -S
Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology 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) K240927
Device Name Access Thyroglobulin
Indications for Use (Describe)
Access Thyroglobulin assay is a paramagetic particle, chemiluminescent immunossay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.
| 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) assigned number: K240927
Submitter Name and Address:
Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318
Primary Contact:
Muhammad Sheikh, Staff Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, MN 55318 Phone: +1 (201) 335-0632 Email:msheikh@beckman.com
Alternate Contact:
Kate Oelberg, Senior Staff Quality and Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, MN 55318 Office Phone: (612) 431-7315 Email:kmoelberg@beckman.com
Date Prepared:
June 20, 2024
Device Name:
Proprietary / Trade Name: Access Thyroglobulin Common Name: Thyroqlobulin Chemiluminescence Immunoassay Classification Description: Tumor-associated antigen immunological test system Classification Requlation: 21 CFR 866.6010 Classification Product Code: MSW
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Predicate Device:
The modified Access Thyroqlobulin assay claims substantial equivalence to previously cleared Access Thyroglobulin assay, FDA 510(k) Number K220972, cleared September 15, 2023.
Device Description:
The Access Thyroglobulin assay consists of the reagent pack and calibrators. Other items needed to run the assay include the Access Thyroglobulin Sample Diluent, substrate and wash buffer. The Access Tg assay along with the Access wash buffer and substrate are designed for use with the Access Immunoassay Systems in a clinical laboratory setting.
Lumi-Phos PRO substrate was used with this pack. The modification does not affect the indications of the device or alter the fundamental scientific technology of the device.
| Well | Ingredients |
|---|---|
| R1a: | Dynabeads* paramagnetic particles coated with streptavidinand coupled to biotinylated mouse monoclonalantithyroglobulin antibodies, suspended in a TRIS buffer withprotein (bovine), < 0.1% sodium azide, and 0.1% ProClin**300. |
| R1b: | Mouse monoclonal anti-thyroglobulin-alkaline phosphatase(bovine) conjugate in a TRIS buffer with protein (bovine,murine), < 0.1% sodium azide, and 0.1% ProClin 300. |
| R1c: | HEPES buffer with protein (bovine and mouse), < 0.1% sodiumazide, and 0.5% ProClin 300. |
A description of the reagent pack is provided below
*Dynabead® is a reqistered trademark of Dynal A.S., Oslo, Norway
**ProClin™ is a trademark of The Dow Chemical Company ("Dow") or an affiliate company of Dow.
Intended Use:
Access Thyroglobulin assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin levels in human serum and plasma using the Access Immunoassay Systems. This device is intended to aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer (DTC) and have had thyroid surgery (with or without ablative therapy), and who lack serum thyroglobulin antibodies.
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Comparison to the Predicate:
The modified device and previously cleared predicate device are compared below.
| Characteristic | Predicate DeviceAccess Thyroglobulin ( K241423) | Modified DeviceAccess Thyroglobulin |
|---|---|---|
| Intended Use | Access Thyroglobulin assay is aparamagnetic particle,chemiluminescent immunoassay forthe quantitative determination ofthyroglobulin levels in human serumand plasma using the AccessImmunoassay Systems. This deviceis intended to aid in monitoring for thepresence of persistent orrecurrent/metastatic disease inpatients who have differentiatedthyroid cancer (DTC) and have hadthyroid surgery (with or withoutablative therapy), and who lackserum thyroglobulinantibodies. | Same |
| AnalyteMeasured | Thyroglobulin | Same |
| Technology | Sandwich immunoassay | Same |
| Format | Chemiluminescent | Same |
| Method | Automated | Same |
| Assayarchitecture | Biotinylated mouse monoclonalantithyroglobulin antibodies pre-coupled to paramagnetic particlescoated with streptavidin | Same |
| Antibodies | Mouse monoclonal antibodies | Same |
| BiotinInterference | No significant interference (± 10%)observed in samples containing up to3,510 ng/mL of biotin. | Same |
| Measuring Range | 0.1 - 500 ng/mL | Same |
| Sample Type | Human serum or plasma | Same |
| Sample Volume | 40 µL | 45 µL |
| Substrate | Access Substrate | Lumi-Phos PRO substrate |
| Instrument | Access 2 Immunoassay Analyzer | Dxl 9000 Access ImmunoassayAnalyzer |
Standard/Guidance Document Referenced (if applicable):
- CLSI EP05-A3: Evaluation of Precision Performance of Quantitative Measurement . Methods; Approved Guideline - Third Edition
- . CLSI EP06-2™ Edition-: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
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- . 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
Summary of Studies:
Method Comparison: A comparison of values using the Access Thyroglobulin assay on Dxl 9000 Immunoassay Analyzer and Access 2 Immunoassay System gave the statistical data provided in the following table. The data was analyzed by Passing-Bablok regression and Pearson's correlation and followed the CLSI EP09c guideline. *Values are from predicate device.
| Dxl 9000Instrument# | N | ConcentrationRange*(ng/mL) | Slope(95% CI) | Intercept(95% CI) | CorrelationCoefficient R |
|---|---|---|---|---|---|
| All Combined | 187 | 0.35 – 4.73 | 1.00(0.99 - 1.00) | 0.0044(-0.029 -0.021) | 1.00 |
*Range is Access 2 values.
Imprecision: The Access Thyroglobulin assay exhibits within laboratory (total) imprecision of CV ≤ 10.0% at concentrations > 1.0 ng/mL and standard deviation (SD) ≤ 0.1 ng/mL at concentrations ≤ 1.0 ng/mL.
A study based on CLSI EP05-A3 performed on a Dxl 9000 Immunoassay Analyzer tested multiple samples in duplicate in 2 runs per day for 20 days. The representative imprecision data is provided in the following table.
| Concentration (ng/mL) | Repeatability(Within-run) | Between-run | Between-day | Within-Laboratory(Total) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 88 | 0.30 | 0.02 | 5.4 | 0.01 | 4.7 | 0.01 | 4.4 | 0.02 | 8.4 |
| Sample 2 | 88 | 5.5 | 0.26 | 4.7 | 0.26 | 4.7 | 0.09 | 1.6 | 0.38 | 6.8 |
| Sample 3 | 88 | 22 | 0.95 | 4.4 | 0.88 | 4.1 | 0.41 | 1.9 | 1.36 | 6.3 |
| Sample 4 | 80 | 111 | 2.22 | 2.0 | 0.64 | 0.6 | 1.47 | 1.3 | 2.74 | 2.5 |
| Sample 5 | 80 | 376 | 8.91 | 2.4 | 5.04 | 1.3 | 9.06 | 2.4 | 13.67 | 3.6 |
| Sample 6 | 80 | 417 | 8.82 | 2.1 | 6.25 | 1.5 | 10.13 | 2.4 | 14.82 | 3.6 |
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Reproducibility: A reproducibility study based on CLSI EP05-A316 performed on the Dxl 9000 Access Immunoassay Analyzer tested multiple samples in replicates of 5 per day for a minimum of 5 days on 3 instruments.
| Concentration (ng/mL) | Repeatability(Within-run) | Between-day | Between -instrument | Reproducibility | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample 1 | 75 | 0.34 | 0.02 | 5.9 | 0.02 | 4.5 | 0.00 | 0.0 | 0.03 | 7.4 |
| Sample 2 | 75 | 6.2 | 0.20 | 3.2 | 0.09 | 1.5 | 0.18 | 2.9 | 0.28 | 4.6 |
| Sample 3 | 75 | 21 | 0.82 | 3.9 | 0.49 | 2.3 | 0.69 | 3.3 | 1.18 | 5.7 |
| Sample 4 | 75 | 109 | 2.98 | 2.7 | 1.62 | 1.5 | 0.92 | 0.8 | 3.51 | 3.2 |
| Sample 5 | 75 | 370 | 11.84 | 3.2 | 6.37 | 1.7 | 13.31 | 3.6 | 18.92 | 5.1 |
| Sample 6 | 75 | 402 | 10.18 | 2.5 | 13.09 | 3.3 | 16.94 | 4.2 | 23.70 | 5.9 |
Linearity: A study based on CLSI EP06-Ed215 performed on the Dxl 9000 Access Immunoassay Analyzer determined the assay demonstrated linearity across the measuring interval.
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Detection Capability: 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 2 instruments over a minimum of 3 days. The LoQ studies included multiple reagent lots and a minimum of 5 days.
| Dxl 9000 ImmunoassayAnalyzer | |
|---|---|
| ng/mL | |
| Limit of Blank (LoB) | 0.03 |
| Limit of Detection (LoD) | 0.05 |
| Limit of Quantitation(LoQ) ≤20% within-labCV | 0.1 |
Conclusion:
The modified device has the same intended use and fundamental scientific technology as the predicate device. The modified device is as safe and effective as the predicate device, as demonstrated through verification testing.
The information provided in this submission demonstrates that the modified device is substantially equivalent to the predicate device.
§ 866.6010 Tumor-associated antigen immunological test system.
(a)
Identification. A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.(b)
Classification. Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.