(18 days)
The ACCESS® Free T4 Assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human or plasma (heparin) using the ACCESS® Immunoassav System. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in human serum or plasma (heparin). Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.
The ACCESS® Free T4 reagents and the ACCESS® Immunoassay Analyzer comprise the ACCESS® Immunoassay System for the quantitative determination of free thyroxine in human serum or plasma (heparin).
The provided document describes the ACCESS® Free T4 assay, an in vitro diagnostic device, and its substantial equivalence to a predicate device for the quantitative determination of free thyroxine. Since this is an in vitro diagnostic device, the acceptance criteria and study designs are different from a typical AI/ML-based medical device that processes images or other patient data. The concepts of "human readers," "AI assistance," "ground truth," "training set," and "test set" in the context of AI/ML are not directly applicable here.
However, I can extract the closest analogous information from the document to answer your questions as best as possible, interpreting the studies described for an in vitro diagnostic device.
Here's a breakdown based on the provided information:
1. Table of Acceptance Criteria and Reported Device Performance
For in vitro diagnostics, "acceptance criteria" usually refer to established performance characteristics that demonstrate the device is fit for its intended use and comparable to existing methods. "Reported device performance" refers to the results obtained from studies evaluating these characteristics.
| Acceptance Criteria Category (Analogous to AI/ML Performance Metric) | Reported Device Performance (Analogous to AI/ML Reported Metric Value) |
|---|---|
| Precision (Within-run %CV) | 3.11% CV (high control) to 4.13% CV (low control) |
| Precision (Total Imprecision %CV) | 4.56% CV (high control) to 7.42% CV (low control) |
| Correlation with Predicate Device (r value) | 0.940 |
| Correlation with Predicate Device (Deming Regression Slope) | 1.16 |
| Correlation with Predicate Device (Deming Regression Intercept) | -0.275 |
| Analytical Sensitivity (Lowest Detectable Level) | 0.15 ng/dL (distinguishable from zero with 95% confidence) |
Note: The acceptance values for these criteria (e.g., what an acceptable r-value or %CV range is) are not explicitly stated in the provided document but are implied by the FDA's clearance based on the reported performance demonstrating substantial equivalence. The predicate device's performance would serve as an implicit benchmark for these.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: 327 samples were used for the correlation study to compare the ACCESS® Free T4 assay with the predicate device (Abbott IMx® Free T4 assay).
- Data Provenance: Not explicitly stated (e.g., country of origin). The document does not specify if the samples were retrospective or prospective, or from a specific demographic.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This concept is not directly applicable to an in vitro diagnostic device like the ACCESS® Free T4 assay, which measures a biochemical marker. The "ground truth" for these devices is typically established through a combination of:
- Reference methods or established predicate devices (as seen in the correlation study).
- Certified calibrators and controls with known analyte concentrations.
- The inherent biochemical process being measured.
There are no "experts" in the sense of human readers/interpreters establishing ground truth for the measurement itself.
4. Adjudication Method for the Test Set
Not applicable. This concept is relevant for studies where human interpretation is involved and discrepancies need to be resolved. For an IVD, the measurement output is quantitative.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. These types of studies are typically performed for imaging or interpretation-based diagnostic devices where multiple human readers evaluate cases, potentially with and without AI assistance, to assess improvements in diagnostic accuracy or efficiency.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies described are essentially "standalone" performance evaluations for the in vitro diagnostic device.
- Precision studies: Evaluate the inherent reproducibility of the device's measurements.
- Analytical Sensitivity: Determines the lowest quantifiable level for the device.
- Correlation study: Compares the device's quantitative outputs directly against those of a predicate device.
The ACCESS® Free T4 assay is a fully automated measurement system (immunoassay analyzer) that provides a quantitative result without direct human interpretation in the measurement process. "Human-in-the-loop" would refer to a scenario where a human modifies or interprets the device's direct output to reach a final diagnosis, which is not the primary function being evaluated here for the measurement system itself. The human-in-the-loop aspect for such devices is typically in the clinician's interpretation of the result in the context of the patient's clinical picture.
7. The Type of Ground Truth Used
For the correlation study, the "ground truth" was established by the results from the predicate device, the Abbott IMx® Free T4 assay. For precision and sensitivity, the "ground truth" relies on the known concentrations of controls and calibrators, which are themselves traceable to established reference methods or standards.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of AI/ML development. For an in vitro diagnostic device, the development process might involve numerous samples for assay optimization, reagent formulation, and initial validation. However, this is distinct from "training data" for an AI algorithm. The 327 samples for the correlation study and the samples used for precision and sensitivity are considered "test" or "validation" samples in this context.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no explicitly defined "training set" in the AI/ML sense for this in vitro diagnostic device. The "ground truth" for developing such assays involves chemical and biological analyses, calibration standards, and comparison to existing validated methods during the development and optimization phases.
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58250
ACCESS® Free T4
Beckman Coulter, Inc.
510(k) Premarket Notification Confidential APPENDIX 4: Summary of Safety and Effectiveness Information
1. General Information
Device Generic Name: Device Trade Name: Applicant's Name and Address: Enzyme Immunoassay, Free T4 ACCESS® Free T4 assay Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, MN 55318
2. Predicate Device
IMx® Free T4 Assay Abbott Laboratories Diagnostics Division Abbott Park, IL 60064
3. Device Description
The ACCESS® Free T4 reagents and the ACCESS® Immunoassay Analyzer comprise the ACCESS® Immunoassay System for the quantitative determination of free thyroxine in human serum or plasma (heparin).
4. Indications for Use
The ACCESS® Free T4 assay is a paramagnetic particle chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human serum or plasma (heparin) using the ACCESS® Immunoassay System.
5. Comparison of Technological Characteristics
Both the ACCESS® Free T4 assay and the Abbott IMx® Free T4 assay measure free thyroxine levels in human serum or plasma (heparin). The ACCESS® Free T4 assay and the Abbott IMx® Free T4 assay are competitive binding immunoassays, utilize particle technology and use a sequential format. Both assays use a T3 alkaline phosphatase conjugate which binds to unoccupied/vacant anti-T4 binding sites. Both assays utilize a four parameter logistic curve (4PLC) data reduction method to generate the curve. Both calibrator sets are prepared in human serum, use a six point calibration, provided in liguid form, and range from 0 - 6 ng/dl. The ACCESS® Free T4 assay binds streplavidin to paramagnetic particles where as the Abbott IMx® Free T4 assay binds anti-T4 to microparticles. The ACCESS® Free T4 assay measures light (photon) production from a chemiluminescent reaction while the Abbott IMx® Free T4 assay measures fluorescence. The ACCESS® Free T4 assay separates the solid phase magnetic particles in a magnetic field during the washing, while the Abbott IMx® Free T4 assay separates the solid phase microparticles by irreversible binding to a glass fiber matrix. The ACCESS®Free T4 assay utilizes a T4 antibody produced in mice while the Abbott IMx® Free T4 assay utilizes a T4 antibody produced in sheep.
6. Summary of Studies
Precision studies: Within run precision ranges from 3.11% CV (high control) to 4.13% CV (low control). Total imprecision ranges from 4.56% CV (high control) to 7.42% CV (low control). Correlation: A comparison of Free T4 values from 327 samples run in both the ACCESS® Free T4 assay and the Abbott IMx® Free T4 assay gives the following statistical data using Deming calculations: r = 0.940, y = 1.16x - 0.275.
Analytical Sensitivity: The lowest detectable level of free T4 distinguishable from zero (ACCESS® Free T4 Calibrator S0) with 95% confidence is 0.15 ng/di.
Conclusion 7.
The ACCESS® Free T4 reagents when used with the ACCESS® Immunoassay Analyzer are substantially equivalent to another test for the measurement of free T4 currently in commercial distribution.
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Image /page/1/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three tail feathers, enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the circle.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUL 1 4 1998
Shellie Gust Requlatory Specialist Beckman Coulter, Inc. 1000 Lake Hazeltine Drive Chaska, Minnesota 55318-1084
Re : K982250 ACCESS® Free T4 Assay on the ACCESS® Immunoassay Analyzer Regulatory Class: II Product Code: CEC, JIS June 24, 1998 Dated: Received: June 26, 1998
Dear Ms. Gust:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act of the Act. include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical General regulation (21 CFR Part 820) and that, Devices: through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or requlations.
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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655 .
This letter will allow you to begin marketing your device as described in your 510 (k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" Other general information on your (21 CFR 807.97). responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.qov/cdrh/dsmamain.html".
Sincerely yours,
Steven Autman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE STATEMENT
Page 1
510(k) Number (if known):
Device Name: ACCESS® Free T4 Reagents on the ACCESS® Immunoassay Analyzer
Indications For Use:
The ACCESS® Free T4 Assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of free thyroxine levels in human or plasma (heparin) using the ACCESS® Immunoassav System.
A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in human serum or plasma (heparin). Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.
(PLEASE DO NOT WRITE BELOW THIS LINE--CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number. K182250
Prescription Use
(Per 21 CFR 801.109)
✓
OR
Over-The Counter Use
§ 862.1695 Free thyroxine test system.
(a)
Identification. A free thyroxine test system is a device intended to measure free (not protein bound) thyroxine (thyroid hormone) in serum or plasma. Levels of free thyroxine in plasma are thought to reflect the amount of thyroxine hormone available to the cells and may therefore determine the clinical metabolic status of thyroxine. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II.