(267 days)
The Access CEA assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of Carcinoembryonic Antigen (CEA) levels in human serum, using the Access Immunoassay Systems. CEA measured by the Access Immunoassay Systems is used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed.
The Access CEA assay is a two-site immunoenzymatic "sandwich" assay using two mouse monoclonal anti-CEA antibodies (MAb) which react with different epitopes of CEA. The Access CEA reagent kit is in a liguid 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 text describes the 510(k) submission for the Beckman Coulter Access CEA assay on the Dxl 9000 Access Immunoassay Analyzer. This document focuses on demonstrating substantial equivalence to a predicate device (Access CEA on the Access Immunoassay Analyzer), primarily through analytical performance studies rather than clinical or AI-assisted diagnostic studies.
Therefore, many of the requested criteria related to AI performance, human reader studies, and expert ground truth are not applicable or cannot be extracted from this document. The information provided is characteristic of a submission for an in vitro diagnostic (IVD) device, which relies heavily on analytical performance characteristics.
Here's the breakdown based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The document provides acceptance criteria and performance for various analytical studies.
| Study Type | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Method Comparison | R² ≥ 0.90 and slope 1.00 ± 0.10 | N=153Concentration Range*: 0.46 - 1071 ng/mLSlope: 0.98Slope 95% Cl: 0.97 - 0.99Intercept: 0.058Intercept 95% Cl: 0.0015 - 0.17Correlation Coefficient R: 1.00The results met the acceptance criteria. |
| Imprecision | (Not explicitly stated in a single overall criterion, but implied to meet industry standards and internal acceptance limits, often expressed as %CV limits for different concentrations.) The acceptance is based on the presented %CV values being acceptable. | Repeatability (Within-run): %CV range 1.8-3.5%Between-run: %CV range 0.8-2.5%Between-day: %CV range 1.2-3.1%Within-Laboratory (Total): %CV range 2.5-5.2% |
| Linearity | Implicitly, results should demonstrate linearity across the stated analytical measuring interval. | The Access CEA assay is linear on the Dxl 9000 Access Immunoassay Analyzer throughout the analytical measuring interval of 0.2 - 1,000 ng/mL. |
| Limit of Blank (LoB) | Implicitly, the estimated LoB should be within acceptable limits (no specific numerical criterion given). | The claimed LoB estimate for the Access CEA assay is 0.09 ng/mL. |
| Limit of Detection (LoD) | Implicitly, the estimated LoD should be within acceptable limits (no specific numerical criterion given). | The claimed LoD estimate for the Access CEA assay is 0.1 ng/mL. |
| Limit of Quantitation (LoQ) | Implicitly, the claimed LoQ should be scientifically justified and within acceptable limits (no specific numerical criterion given). | The claimed LoQ determined for Access CEA assay is 0.2 ng/mL. |
2. Sample size used for the test set and the data provenance:
- Method Comparison: A total of 153 serum samples were evaluated.
- Imprecision: Multiple samples (7 distinct concentration levels) were tested with a minimum of three replicates in 2 runs per day for a minimum of 20 days. The "N" column in the table refers to the total number of measurements for each sample level (e.g., 126 for Sample 1, 120 for Sample 2, etc.).
- Data Provenance: The document does not specify the country of origin of the data or whether the samples were retrospective or prospective. This is typical for IVD analytical performance studies.
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 this type of device and study. The ground truth for analytical performance studies like Method Comparison, Imprecision, Linearity, LoB, LoD, and LoQ is established by the reference measurement method (in this case, the predicate device for method comparison, or precise measurements by the instrument itself for other analytical characteristics) and laboratory standards, not by expert human interpretation like a radiologist reading an image.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- This is not applicable. Adjudication methods are used in studies involving human interpretation or challenging diagnoses, not for analytical performance of an IVD assay measuring a biomarker concentration.
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:
- This is not applicable. This is an in vitro diagnostic device (immunoassay for CEA), not an AI-powered image analysis or diagnostic assist device for human readers. No human interpretation or AI assistance study was performed or required for this type of submission.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This is not applicable in the context of AI algorithms. The device itself (Access CEA assay on the Dxl 9000 Access Immunoassay Analyzer) is a standalone automated analytical instrument. Its performance is evaluated as an "algorithm only" in the sense that it performs the measurement independently, but it's a chemical and optical measurement process, not an AI algorithm.
7. The type of ground truth used:
- For the Method Comparison study, the "ground truth" or reference method was the predicate device (Access CEA on the Access Immunoassay Analyzer).
- For other analytical studies (Imprecision, Linearity, LoB, LoD, LoQ), the ground truth is established through controlled spiking, dilutions, and repeated measurements according to established analytical validation guidelines (e.g., CLSI EP-05-A3 for imprecision). These are intrinsic analytical properties of the assay and instrument combination, verified against laboratory standards.
8. The sample size for the training set:
- This is not applicable as this is not an AI/machine learning device that requires a "training set" in the conventional sense. The development of an immunoassay involves optimizing reagents, antibodies, and instrument parameters, which is a different process from training a machine learning model.
9. How the ground truth for the training set was established:
- This is not applicable for the reasons stated in point 8.
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September 22, 2023
Beckman Coulter, Inc Kuljeet Kaur Manager, Regulatory Affairs 1000 Lake Hazeltine Drive Chaska, Minnesota 55318
Re: K223921
Trade/Device Name: Access CEA Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: DHX Dated: August 23, 2023 Received: August 23, 2023
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/cfpmr/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
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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 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 (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
Enclosure
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Indications for Use
510(k) Number (if known) K223921
Device Name Access CEA
Indications for Use (Describe)
The Access CEA assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of Carcinoembryonic Antigen (CEA) levels in human serum, using the Access Immunoassay Systems. CEA measured by the Access Immunoasay Systems is used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed.
| 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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Access CEA 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: K223921
Submitter Name and Address:
Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318
Primary Contact:
Abhi Kannan, Staff Regulatory Affairs Phone: +1 (905) 556 0843 Email: Akannan01@beckman.com
Alternate Contact:
Kuljeet Kaur, Senior Manager Regulatory Affairs Phone: (952) 465-1914 Email: kkaur@beckman.com
Trade Name: Access CEA Common Name: Carcinoembryonic Antigen Assay Classification Name: Tumor-associated antigen immunological test system Classification Regulation: 21 CFR 866.6010 Classification Product Code: DHX
Predicate Device: Access CEA 510(k) numbers: K991707 and K981985
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Device Description
The Access CEA assay is a two-site immunoenzymatic "sandwich" assay using two mouse monoclonal anti-CEA antibodies (MAb) which react with different epitopes of CEA. The Access CEA reagent kit is in a liguid 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 CEA assay is a paramaqnetic particle, chemiluminescent immunoassay for the quantitative determination of Carcinoembryonic Antigen (CEA) levels in human serum, using the Access Immunoassay Systems. CEA measured by the Access Immunoassay Systems is used as an aid in the management of cancer patients in whom changing CEA concentrations have been observed.
| Characteristic | Access CEA onAccess Immunoassay Analyzer(Predicate) | Access CEA Assay onDxl 9000 AccessImmunoassay Analyzer(Candidate) |
|---|---|---|
| Intended use | The Access CEA assay is aparamagnetic particle,chemiluminescent immunoassay forthe quantitative determination ofCarcinoembryonic Antigen (CEA)levels in human serum, using theAccess Immunoassay Systems.CEA measured by the AccessImmunoassay Systems is used asan aid in the management of cancerpatients in whom changing CEAconcentrations have been observed. | Same |
| Analyte Measured | Carcinoembryonic Antigen (CEA) inhuman serum | Same |
| Technology | One-step sandwich | Same |
| Format | Chemiluminescent | Same |
| Method | Automated | Same |
| Calibrators | Multi-point calibrators containingpurified CEA Human in a phosphatebuffered BSA matrix withpreservatives. | Same |
Comparison of Technological Characteristics to the Predicate
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| Characteristic | Access CEA onAccess Immunoassay Analyzer(Predicate)Access CEA Assay onDxl 9000 AccessImmunoassay Analyzer(Candidate) |
|---|---|
| Calibration | Utilizes a stored calibration curveSame |
| QC Controls | Bi-level controls containing humanCEA in a phosphate buffered BSAmatrix with preservativesSame |
| Sample Type | SerumSame |
| Antibody | Monoclonal (mouse) anti-humanCEA antibodiesSame |
| Reagent Stability | Stable at 2 to 10°C for 28 days afterinitial useSame |
| Measuring Range | ~0.1 – 1,000 ng/mL0.2 — 1,000 ng/mL |
| Substrate | Access SubstrateLumi-Phos PRO substrate |
| Instrument | Access 2 Immunoassay systemDxl 9000 AccessImmunoassay Analyzer |
Summary of Studies
Method Comparison: A method comparison study was performed to compare the Access CEA Assay on Dxl 9000 Access Immunoassay Analyzer to the predicate device. A total of one hundred and fifty-three (153) serum samples falling within the measuring range of the Access CEA 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 | Slope 95%Cl | Intercept | Intercept 95%Cl | CorrelationCoefficient R |
|---|---|---|---|---|---|---|
| 153 | 0.46 -1071 | 0.98 | 0.97 - 0.99 | 0.058 | 0.0015 - 0.17 | 1.00 |
*Range is Access 2 values
Imprecision: Verification studies were performed to determine the imprecision of the Access CEA assay on the Dxl 9000 Access Immunoassay Analyzer using a protocol based CLSI EP-05-A3 with multiple samples with minimum of three replicates in 2 runs per day for a minimum of 20 days.
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| Concentration (ng/mL) | Repeatability(Within-run) | Between-run | Between-day | Within- Laboratory(Total) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 126 | 0.45 | 0.02 | 3.5 | 0.01 | 1.5 | 0.01 | 2.0 | 0.02 | 4.3 |
| 2 | 120 | 5.1 | 0.10 | 2.1 | 0.04 | 0.8 | 0.06 | 1.2 | 0.13 | 2.5 |
| 3 | 126 | 11 | 0.2 | 1.9 | 0.3 | 2.5 | 0.2 | 1.5 | 0.4 | 3.5 |
| 4 | 120 | 89 | 1.9 | 2.2 | 0.8 | 0.9 | 1.1 | 1.3 | 2.4 | 2.7 |
| 5 | 120 | 153 | 2.8 | 1.8 | 1.9 | 1.3 | 2.3 | 1.5 | 4.1 | 2.7 |
| 6 | 120 | 525 | 18.5 | 3.5 | 6.6 | 1.2 | 16.0 | 3.1 | 25.3 | 4.8 |
| 7 | 120 | 865 | 22.4 | 2.6 | 5.3 | 0.6 | 38.6 | 4.5 | 45.0 | 5.2 |
Linearity: The Access CEA assay is linear on the Dxl 9000 Access Immunoassay Analyzer throughout the analytical measuring interval of 0.2 - 1,000 ng/mL.
Limit of Blank (LoB): The claimed LoB estimate for the Access CEA assay is 0.09 ng/mL on the Dxl 9000 Access Immunoassay Analyzer.
Limit of Detection (LoD): The claimed LoD estimate for the Access CEA assay is 0.1 ng/mL on the Dxl 9000 Access Immunoassay Analyzer.
Limit of Quantitation (LoQ): The claimed LoQ determined for Access CEA assay is 0.2 ng/mL on the Dxl 9000 Access Immunoassay Analyzer.
Substantial Equivalence Comparison Conclusion
Beckman Coulter's Access CEA Assay on the Dxl 9000 Access Immunoassay Analyzer is substantially equivalent to the Access CEA 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.
§ 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.