(77 days)
Immunoassay for the in vitro quantitative determination of α₁-fetoprotein in human serum and plasma to aid in the management of patients with non-seminomatous germ cell tumors. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys immunoassay analyzers.
The Elecsys® test principle is based on the sandwich principle. Total duration of assay: 18 minutes. 1st incubation: 15 µl of sample, a biotinylated monoclonal AFP-specific antibody and a monoclonal AFP-specific antibody labeled with a ruthenium complex react to form a sandwich complex. 2nd incubation: after the addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin. The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier. Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided via the reagent bar code.
Here's a breakdown of the acceptance criteria and study information for the Elecsys AFP device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The provided text for K973351 primarily describes the device and its comparison to a predicate device, but it does not explicitly state specific numerical acceptance criteria for each performance characteristic. Instead, it lists the types of studies performed to demonstrate substantial equivalence.
However, based on the types of studies listed, we can infer the aspects of performance that were evaluated and for which the device was considered acceptable. The "Reported Device Performance" below reflects what the submission claims to have demonstrated.
| Performance Characteristic | Acceptance Criteria (Inferred from Study Type) | Reported Device Performance (Summary from Submission) |
|---|---|---|
| Precision | To meet NCCLS recommendations | Evaluated according to NCCLS recommendations. (Details not provided in the summary, but implies acceptable precision.) |
| Lower Detection Limit | To be accurately determinable | Determined. (Specific value not provided, but implies acceptable sensitivity for clinical use.) |
| Linearity | To demonstrate linear response across range | Demonstrated. (Implies a reliable and proportional measurement across its intended assay range.) |
| Correlation with Predicate | To show substantial equivalence | Correlated with the predicate device (Enzymun-Test® AFP). (Implies comparable results to the reference method.) This was further supported by comparisons with samples from serially monitored patients diagnosed and treated for testicular cancer. |
| Interference (Endogenous) | No significant interference in results | Evaluated for the effect of various endogenous substances (hemoglobin, biotin, triglyceride, lipemia, and rheumatoid factor). (Implies no significant interference found, or interference within acceptable limits.) |
| Interference (Pharmaceutical) | No significant interference in results | Evaluated for the effect of commonly used pharmaceutical compounds. (Implies no significant interference found, or interference within acceptable limits.) |
| Sample Matrix Equivalence | Serum and plasma results to be comparable | Serum and plasma sample comparisons performed. (Implies comparable performance between serum and plasma samples.) |
| Hook Effect | To be determined (and generally absent/managed) | Determination of hook effect. (Implies the device handles very high concentrations without false low readings, or that the effect is understood and managed if present.) |
| Stability | To ensure reliable performance over time | Stability studies performed. (Implies the device maintains its performance characteristics over its stated shelf-life and in-use periods.) |
| Clinical Performance | Aid in patient management (comparable to predicate) | Comparisons of the Elecsys AFP and the predicate device were performed with samples from serially monitored patients diagnosed and treated for testicular cancer. (This surrogate for clinical utility demonstrates that the new device performs similarly in a real-world clinical context to the approved predicate, thus reasonably aiding in patient management.) |
2. Sample Size Used for the Test Set and Data Provenance
The submission does not explicitly state the numerical sample sizes used for the various tests mentioned (precision, linearity, interference, etc.). It only describes the types of studies performed.
The data provenance is not explicitly mentioned (e.g., country of origin). The studies appear to be retrospective in nature, as they involve comparisons with an existing predicate device and samples from "serially monitored patients diagnosed and treated for testicular cancer," suggesting pre-collected samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the submission. For an in vitro diagnostic (IVD) like the Elecsys AFP, the "ground truth" for performance studies typically comes from reference methods (like the predicate device) or known concentrations/spiked samples, rather than human expert interpretation of images or clinical data. However, the diagnosis of "testicular cancer" in the patient samples would have been established by medical professionals, but the details of who and how many are not discussed in relation to the device's technical validation.
4. Adjudication Method for the Test Set
This is not applicable and therefore not mentioned for this type of IVD device. Adjudication methods (like 2+1, 3+1) are typically used in studies involving human readers or interpretation of complex medical data (e.g., imaging studies) where there might be inter-reader variability in establishing ground truth. For an automated immunoassay, the "ground truth" is established through analytical methods and reference standards.
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
No, an MRMC comparative effectiveness study was not conducted and is not applicable for this type of IVD device. This device is an automated immunoassay, not an AI-powered diagnostic image analysis tool that assists human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies described are standalone performance evaluations of the Elecsys AFP immunoassay. The device itself is an automated system for quantitative determination of AFP; there is no human-in-the-loop in the assay run or measurement process. Results are then interpreted by clinicians, but the device's performance characteristics (precision, linearity, correlation, etc.) are inherent to the algorithm and instrument.
7. The Type of Ground Truth Used
The ground truth used for various aspects of the study includes:
- Reference materials/standards: For linearity, lower detection limit, and potentially stability, calibrated reference materials or spiked samples of known concentrations would be used.
- Predicate device: The Enzymun-Test® AFP served as the primary "ground truth" or reference for comparative performance (correlation).
- Known clinical status: For the patient sample comparisons, the "serially monitored patients diagnosed and treated for testicular cancer" represent samples with a known clinical diagnosis, allowing for comparison of the new device's performance in a clinically relevant population against the predicate.
8. The Sample Size for the Training Set
This information is not applicable and therefore not provided. The Elecsys AFP is a chemistry immunoassay, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. The "calibration curve" is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code; this is a form of calibration, not model training.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, there is no "training set" in the context of machine learning for this device. The closest equivalent would be the calibration process. The ground truth for this would be:
- Calibrators with known, traceable concentrations: Used to establish the device's response curve. The master curve is provided via the reagent bar code, implying that the manufacturer pre-established the curve characteristics using highly controlled and validated calibrators.
- 2-point calibration: This periodic user calibration adjusts the master curve to account for minor variations in reagents or instrument performance, using calibrators with known values.
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| BOEHRINGERMANNHEIMCORPORATION | |
|---|---|
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
| 1) Submitter name, address, contact | Boehringer Mannheim Corporation2400 Bisso LaneConcord, CA 94524-4117(317) 845-2000Contact Person: Patricia M. KlimleyDate Prepared: September 2, 1997 |
|---|---|
| 2) Device name | Proprietary name: Elecsys® AFPCommon name: Alpha-Fetoprotein assayClassification name: Alpha-Fetoprotein test kit for testicular cancer |
| 3) Predicate device | We claim substantial equivalence to the Enzymun-Test® AFP (P860044). |
| 4) Device Description | The Elecsys® test principle is based on the sandwich principle. Total duration of assay: 18 minutes. 1st incubation: 15 µl of sample, a biotinylated monoclonal AFP-specific antibody and a monoclonal AFP-specific antibody labeled with a ruthenium complex react to form a sandwich complex.2nd incubation: after the addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin. |
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510(k) Summary, Continued
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| 4) Device Description, cont. | The reaction mixture is aspirated into the measuring cell where the micro- particles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier. Results are determined via a calibration curve which is instrument- specifically generated by 2-point calibration and a master curve provided via the reagent bar code. | |
|---|---|---|
| 5) Intended use | Immunoassay for the in vitro quantitative determination of α₁-fetoprotein in human serum and plasma to aid in the management of patients with non- seminomatous germ cell tumors. | |
| 6) Comparison to predicate device | The Boehringer Mannheim Elecsys AFP is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Enzymun-Test AFP.Studies performed include: evaluation of assay precision according to NCCLS recommendations determination of the lower detection limit demonstration of linearity correlation with the predicate device evaluation of the effect of various endogenous substances (hemoglobin, biotin, triglyceride, lipemia, and rheumatoid factor), and commonly used pharmaceutical compounds and serum plasma sample comparisons. determination of hook effect, and stability studies. In addition, comparisons of the Elecsys AFP and the predicate device were performed with samples from serially monitored patients diagnosed and treated for testicular cancer. |
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 2 1 1997
Ms. Patricia M. Klimley Manager, Requlatory Affairs Boehringer Mannheim Corporation 2400 Bisso Lane Concord, California 94524-4117
Re: K973351 Trade Name: Elecsys® AFP Regulatory Class: II Product Code: LOJ Dated: September 2, 1997 September 5, 1997 Received:
Dear Ms. Klimley:
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 of the Act. 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.
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 Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. 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 Regulations.
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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" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Putman
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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510(k) Number (if known): Device Name: Elecsys® AFP Indications for Use:
Immunoassay for the in vitro quantitative determination of &;-fetoprotein in human serum and plasma to aid in the management of patients with non-seminomatous germ cell tumors.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys immunoassay analyzers.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use__
(Optional Format 1-2-96)
§ 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.