(90 days)
Enzyme-linked immunosorbent assay for the quantitative determination of Prostate-Specific Antigen (PSA) in serum and plasma.
The Enzymun-Test PSA test principle is an ELISA/1-step sandwich assay using streptavidin technology. The assay procedure is designed to run on the Boehringer Mannheim Automated Immunoassay Systems.
In the first incubation step (immunological reaction) the PSA in the sample reacts with the biotinylated anti-PSA antibodies, which are in turn bound to the streptavidin-coated tube wall. The PSA is also bound to the peroxidase (POD)-labeled monoclonal antibody (anti-PSA POD-conjugate) to form a sandwich complex. The quantity of antibody-PSA POD complex formed is a measure of the PSA content of the sample. The unbound POD-conjugate is removed along with serum constituents in the separation step.
The activity of the POD bound to the tube wall is determined photometrically after the addition of the chromogen and the substrate H2O2 (from sodium perborate). In the indicator reaction, the chromophore formed is a dark green cation whose concentration is directly proportional to the PSA concentration in the sample. The color intensity that develops within a fixed period of time is measured against the substrate/chromogen blank.
The test results are determined from a calibration curve derived using the standards provided in the kit.
This document describes the Enzymun-Test® PSA device, an enzyme-linked immunosorbent assay (ELISA) for the quantitative determination of Prostate-Specific Antigen (PSA) in serum and plasma, and its comparison to a predicate device, the Hybritech Tandem®-R PSA (a radioimmunoassay).
1. Table of Acceptance Criteria (Implied) and Reported Device Performance
The acceptance criteria are not explicitly stated as pass/fail thresholds but are implied by the performance characteristics presented and comparison to the predicate device. The study's goal is to demonstrate "substantial equivalence" to the predicate device. Therefore, the reported performance of the Enzymun-Test® PSA is compared directly against the Hybritech Tandem®-R PSA.
| Feature | Acceptance Criteria (Implied by Predicate) | Reported Device Performance (Enzymun-Test® PSA) |
|---|---|---|
| Precision (within-run CV) | Similar to Hybritech Tandem-R PSA (e.g., 1.1% - 2.7%) | Pool 1: 6.0%; Pool 2: 3.0%; Pool 3: 2.6%; TMI: 3.4%; TMII: 3.0% |
| Precision (total CV) | Similar to Hybritech Tandem-R PSA (e.g., 3.2% - 5.6%) | Pool 1: 15.2%; Pool 2: 4.3%; Pool 3: 4.4%; TMI: 5.0%; TMII: 4.0% |
| Sensitivity (Lower Detection Limit) | Similar or better than Hybritech Tandem-R PSA (0.15 ng/ml) | 0.05 ng/ml (Better) |
| Assay Range | Similar or better than Hybritech Tandem-R PSA (0.15 ng/ml - 100 ng/ml) | 0.05 ng/ml - 50 ng/ml (Lower upper limit, better lower limit) |
| Interfering Substances | Similar or better interference tolerance than Hybritech Tandem-R PSA | |
| Hemoglobin | Up to 200 mg/dl (Hybritech) | No interference up to 700 mg/dl (Better) |
| Bilirubin | Up to 25 mg/dl (Hybritech) | No interference up to 64.5 mg/dl (Better) |
| Lipemia | Up to 2320 mg/dl (Hybritech) | No interference up to 1250 mg/dl (Intralipid) (Lower, but different substance) |
2. Sample Size Used for the Test Set and Data Provenance
- Precision (Enzymun-Test PSA):
- Within-run: N = 63 for each of 5 pools (Pool 1, Pool 2, Pool 3, TMI, TMII). This was for 20 replicates from 3 runs (N=63 seems to represent total measurements across runs).
- Total: N = 63 for each of 5 pools.
- Precision (Hybritech Tandem-R PSA - for comparison):
- Within-run: N = 60 for each of 3 pools.
- Between-run: N = 201 for each of 3 pools.
- Inter-laboratory: N = 8 for each of 4 pools.
The document does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of device is an in vitro diagnostic (IVD) for quantitative measurement. The "ground truth" for the test set is established by the measured values themselves, typically compared to reference methods or the predicate device. Therefore, the concept of "experts establishing ground truth" as it applies to image interpretation or clinical diagnosis by human experts is not directly relevant here. The gold standard for quantitative measurements like PSA would be the result from a qualified laboratory using established methods.
4. Adjudication Method for the Test Set
Not applicable. As this is a quantitative analytical device, measurement is the outcome, not an expert panel adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret results (e.g., imaging devices with radiologists). The Enzymun-Test® PSA is an automated immunoassay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, the performance characteristics provided are for the standalone device (Enzymun-Test® PSA system). It's an automated assay, so its performance is inherently "standalone" in terms of measurement. Human-in-the-loop primarily involves sample preparation and loading, and interpreting the quantitative result within a clinical context (which is outside the scope of the device's analytical performance itself).
7. The Type of Ground Truth Used
The ground truth for evaluating analytical performance (precision, sensitivity, assay range, interference) is based on:
- Known concentrations: For precision, samples of known concentrations (pools) are used.
- Comparison to a predicate device: The Hybritech Tandem®-R PSA serves as the comparator to demonstrate substantial equivalence, implying its results are considered a valid reference or "ground truth" for comparative purposes.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of device development or algorithm training. For an immunoassay like this, the development process involves reagent optimization, calibration curve establishment, and assay validation, which would involve numerous samples, but these are not typically referred to as a "training set" in the same way as machine learning.
9. How the Ground Truth for the Training Set Was Established
Not applicable in the context of a traditional immunoassay device. The "ground truth" would be established by the reference methods and known concentrations used during the assay development and calibration process.
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K96 5085
票
MAR | 9 |997
510(k) Summary
| 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 Corporation9115 Hague Rd.Indianapolis, IN 46250(317) 845-2000 |
| Contact Person: LeeAnn Chambers | |
| Date Prepared: November 15, 1996 | |
| 2) Device name | Proprietary name: Enzymun-Test® PSA |
| Common name: tumor associated antigen immunological test system | |
| Classification name: Prostate-specific antigen (PSA), immunological test system for the management of prostate cancer | |
| 3) Predicate device | We claim substantial equivalence to the Hybritech Tandem®-R PSA (P850048). |
| 4) Device Description | The Enzymun-Test PSA test principle is an ELISA/1-step sandwich assay using streptavidin technology. The assay procedure is designed to run on the Boehringer Mannheim Automated Immunoassay Systems. |
| In the first incubation step (immunological reaction) the PSA in the sample reacts with the biotinylated anti-PSA antibodies, which are in turn bound to the streptavidin-coated tube wall. The PSA is also bound to the peroxidase (POD)-labeled monoclonal antibody (anti-PSA POD-conjugate) to form a sandwich complex. The quantity of antibody-PSA POD complex formed is a measure of the PSA content of the sample. The unbound POD-conjugate is removed along with serum constituents in the separation step. |
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510(k) Summary, Continued
| 4) Device Description, (cont.) The activity of the POD bound to the tube wall is determined photometrically after the addition of the chromogen and the substrate H2O2 (from sodium perborate). In the indicator reaction, the chromophore formed is a dark green cation whose concentration is directly proportional to the PSA concentration in the sample. The color intensity that develops within a fixed period of time is measured against the substrate/chromogen blank.The test results are determined from a calibration curve derived using the standards provided in the kit. |
|---|
| 5) Intended use Enzyme-linked immunosorbent assay for the quantitative determination of Prostate-Specific Antigen (PSA) in serum and plasma. |
| 6) Comparison to predicate device The Boehringer Mannheim Enzymun-Test PSA is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Hybritech Tandem-R PSA.The following table compares the Enzymun-Test PSA with the predicate device Hybritech Tandem-R PSA.Similarities: Intended use: for the quantitative measurement of prostate-specific antigen (PSA) to aid in the prognosis and management of patients with prostate cancer. Both assays use mouse monoclonal antibodies to bind and detect PSA Both assays use 50 $μ$ l sample volume. |
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510(k) Summary, Continued
- Comparison Differences: to predicate device, (cont.)
.
| Feature | Enzymun-Test PSA | Hybritech Tandem-R PSA |
|---|---|---|
| Sample type | Human serum and plasma | Human serum |
| Detectionmethod | Enzyme linkedimmunosorbent assay | Radioimmunoassay |
| Instrumentrequired | ES 300 or other ES system | γ-PHOTON System or gammacounter |
| Calibration | Full calibration curve every 2weeks with a 1 pointrecalibration with every run | Full calibration curve withevery run |
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Performance Characteristics:
| Feature | Enzymun-Test PSA | Hybritech Tandem-R PSA | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Precision | NCCLS EP5-T2 protocol | within run: (20 replicates from 3 runs) | |||||||||
| within run: | |||||||||||
| Pool 1 | Pool 2 | Pool 3 | TMI | TMII | 1 | 2 | 3 | ||||
| N | 63 | 63 | 63 | 63 | 63 | N | 60 | 60 | 60 | ||
| x̄ | 0.28 | 3.07 | 39.64 | 1.19 | 6.43 | x̄ | 2.98 | 6.99 | 36.34 | ||
| CV | 6.0 | 3.0 | 2.6 | 3.4 | 3.0 | CV | 2.7 | 1.6 | 1.1 | ||
| Total: | between run: | ||||||||||
| Pool 1 | Pool 2 | Pool 3 | TMI | TMII | 1 | 2 | 3 | ||||
| N | 63 | 63 | 63 | 63 | 63 | N | 201 | 201 | 201 | ||
| x̄ | 0.28 | 3.07 | 39.64 | 1.19 | 6.43 | x̄ | 3.05 | 7.14 | 35.71 | ||
| CV | 15.2 | 4.3 | 4.4 | 5.0 | 4.0 | CV | 5.6 | 3.2 | 3.7 | ||
| inter-laboratory: | |||||||||||
| 1 | 2 | 3 | 4 | ||||||||
| N | 8 | 8 | 8 | 8 | |||||||
| x̄ | 3.06 | 13.27 | 31.48 | 83.59 | |||||||
| CV | 5.56 | 5.12 | 4.42 | 2.64 | |||||||
| Sensitivity | Lower detection limit:0.05 ng/ml | Minimum detectable conc.:0.15 ng/ml | |||||||||
| Assay range(LDL tohigheststandard) | 0.05 ng/ml - 50 ng/ml | 0.15 ng/ml - 100 ng/ml | |||||||||
| InterferingSubstances | No interference up to: | No interference up to: | |||||||||
| hemoglobin | 700 mg/dl | 200 mg/dl | |||||||||
| bilirubin | 64.5 mg/dl | 25 mg/dl | |||||||||
| lipemia | 1250 mg/dl (Intralipid) | 2320 mg/dl |
§ 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.