(158 days)
The IOS Prostate Specific Antigen Test Cartridges are to be used for the quantitative determination of prostate specific antigen levels in serum as an aid in the management of patients diagnosed with prostate cancer. They are intended to be used with the IOS instrument in clinical laboratories, physicians' office laboratories, and other alternate sites of use close to the point of patient care.
The IOS PSA Controls are to be used to assist in monitoring accuracy and precision in the IOS PSA Test Cartridges.
Prostate Specific Antigen Test Cartridges:
Prostate specific antigen (PSA) is a serine protease first discovered in seminal plasma which has a molecular weight of approximately 30,000 Daltons. 14 PSA is secreted by normal prostatic epithelial cells as well as by diseased prostatic tissue. When PSA is released into the blood, it is inactivated by the major extracellular serine protease inhibitors, alpha-2-macroglobulin and alpha-1-antichymotrypsin. The portion of PSA that is inactivated by alpha-2-macroglobulin is undetectable by immunoassays measuring total PSA.46 The fraction of PSA bound to alpha-1-antichymotrypsin (~90 kDa) is detectable and is the predominate form of PSA in human serum, constituting 73 -95% of circulating PSA. The remaining 5 - 27% of detectable PSA exists in a "free" enzymatically inactive state (~30 kDa), and is found to be at higher proportions in patients with benign prostatic hyperplasia. The IOS PSA assay measures free and total PSA in an equimolar fashion.
Longitudinal determinations of PSA have been shown to be useful when monitoring prostate cancer patients. Serial PSA measurements are indicative of recurrence of disease or metastatic progression if PSA levels continue to rise after surgical or medical treatment. Serial PSA measurements that decrease to undetectable levels indicate successful treatment of disease.8-11
PSA levels have also been shown to be elevated in patients with benign prostatic hyperplasia (BPH) and prostatitis. 10 PSA levels are not elevated in cancers of the breast, lung, colon, rectum, stomach, pancreas, or thyroid.
PSA testing alone is not be used as a screening test for prostate cancer or in the staging of prostatic cancer. PSA testing is accepted as an adjunctive test in managing the treatment of patients with prostate cancer. 12,13
Principle of the Test
The IOS PSA test is a two-site sandwich immunoassay. PSA in the patient serum binds to an enzyme-labeled monoclonal anti-PSA conjugate. This PSA:conjugate complex is captured by polyclonal anti-PSA antibody immobilized on the plastic surface, forming a capture-antigen-conjugate sandwich. After an incubation period, excess sample and conjugate are washed away and substrate is added. The substrate reacts with the conjugate: PSA complex captured on the surface and produces a fluorescent signal. The rate of the enzyme-substrate reaction is directly proportional to the amount of conjugate bound, which is directly proportional to the amount of PSA present in the patient sample. All reagents necessary to perform the test are dried on the IOS test cartridge, and are rehydrated by the addition of patient sample, or by the addition of IOS buffer by the instrument.
To perform the test, the operator inserts an IOS PSA cartridge into the IOS instrument. When prompted, the operator adds sample to the sample well and starts the test sequence. The instrument draws the cartridge inside to mix the patient sample, which also rehydrates the anti-PSA conjugate. A short incubation period allows the serum and conjugate to react. The PSA:conjugate complex then flows into the incubation/reaction chamber where binding to the solid phase occurs. At the end of this incubation time, excess patient sample and conjugate are aspirated out of the incubation/reaction chamber and the incubation/reaction chamber is washed using buffer added by the instrument. Buffer is also used to rehydrate the substrate necessary for signal generation and quantitation of PSA in another reagent chamber; rehydrated substrate is then allowed to enter the incubation/reaction chamber. The fluorescent signal produced is read as a rate by front-surface fluorometry, compared to the rates produced by a series of calibrators stored in the instrument memory, and the amount of PSA present in the patient sample is calculated from the stored calibration curve.
IOS PSA Controls: The use of materials derived from human blood to monitor quality control of clinical chemistry testing in the clinical laboratory has been widely established over the past several years. The Biocircuits IOS PSA Controls are two levels of bloodbased material for use with Biocircuits IOS PSA Test Cartridges.
To run a control, the operator inserts the Control Cartridge (packaged with the controls) into the IOS instrument. The instrument reads the lot number and ranges of acceptable values for the control solutions from the Control Cartridge barcode, and then ejects the Control Cartridge. The operator then inserts a test cartridge and follows the instrument prompts to identify the control level, apply control solutions, and begin the test sequence. The IOS instrument performs the required buffer additions to rehydrate assay reagents and perform wash steps as necessary, reads the fluorescence signal generated, and calculates and prints the control result just as it would if the cartridge were used to test a patient sample.
Here's an analysis of the provided text to extract the acceptance criteria and study details for the Biocircuits IOS® PSA Test Cartridges:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria | Reported Device Performance (Biocircuits IOS® PSA Test Cartridges) |
|---|---|
| Precision | |
| Control Level 1: | Mean: 2.6 ng/mL |
| %CV, within-day | 11.3% (n=10) |
| %CV, between-day | 10.0% (n=10 days) |
| %CV, overall | 10.2% |
| Control Level 2: | Mean: 10.1 ng/mL |
| %CV, within-day | 5.5% (n=10) |
| %CV, between-day | 12.8% (n=10 days) |
| %CV, overall | 12.4% |
| Control Level 3: | Mean: 23.3 ng/mL |
| %CV, within-day | 7.6% (n=10) |
| %CV, between-day | 8.6% (n=10 days) |
| %CV, overall | 9.7% |
| Accuracy | Correlation coefficient ('r') = 0.9924 |
| Regression equation: y = 0.99 * x + 0.35 | |
| Measuring Range | 0.2 to 95.8 ng/mL (samples tested) |
Note: The document explicitly states the "Performance Data" which includes precision and accuracy. While the document presents these as "results" rather than explicit "acceptance criteria," in the context of a 510(k) summary, these are the performance metrics the manufacturer submits to demonstrate the device's capability and equivalence to a predicate. The predicate device's performance would generally set the benchmark for these implicit acceptance criteria.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: 319 patient samples were used for the accuracy study (comparison of methods).
- Data Provenance: The studies were "performed in the manufacturer's laboratories." The document does not specify the country of origin of the data or whether it was retrospective or prospective, but the context of an in vitro diagnostic device for PSA testing suggests that these were likely collected clinical samples.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
This information is not provided in the document. For in vitro diagnostic devices like this PSA test, the "ground truth" for accuracy is typically established by comparison to a recognized reference method or a legally marketed predicate device, rather than expert consensus on interpretive tasks. In this case, the accuracy was determined by comparing the IOS PSA assay to "a commercially available enzyme immunoassay." The qualifications of those who ran the comparative assay are not detailed.
4. Adjudication Method for the Test Set
This information is not applicable to this type of in vitro diagnostic device study. Adjudication methods (like 2+1, 3+1) are typically used in clinical imaging studies or other diagnostic areas where human interpretation can be subjective and independent expert review is needed to establish a consensus ground truth. For an immunoassay, the result is quantitative and directly measured by a machine.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance
This information is not applicable to this device. An MRMC study is relevant for evaluating the impact of AI on diagnostic tasks performed by human readers (e.g., radiologists, pathologists). The Biocircuits IOS® PSA Test Cartridges are an in vitro diagnostic assay that provides a quantitative measurement of PSA; it does not involve human readers interpreting AI output.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the performance data presented (Precision and Accuracy) represent the standalone performance of the IOS PSA assay system. The device itself performs the measurement and calculates the PSA level. There is no human-in-the-loop component for the measurement of PSA by the device, although a human operates the device and interprets the numerical result in the context of a patient's clinical management.
7. The Type of Ground Truth Used
For the accuracy study, the ground truth was effectively established by comparison to a "commercially available enzyme immunoassay." This predicate or reference method served as the comparative "truth" against which the new device's measurements were evaluated. The range of samples tested was from 0.2 to 95.8 ng/mL.
8. The Sample Size for the Training Set
This information is not provided in the document. The Biocircuits IOS® PSA Test Cartridges are a chemical immunoassay, not an AI/machine learning algorithm that requires a "training set" in the conventional sense. The "training" in this context would refer to method development, reagent optimization, and calibration curve generation, which is a different paradigm than AI model training.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" with established "ground truth" in the AI sense does not directly apply here. For immunoassays, the equivalent would be the development of calibrators and quality control materials. The document states that the calibration is "Factory-generated" and calibrated against "a series of calibrators stored in the instrument memory." The ground truth for these calibrators would typically be established through highly accurate reference methods or certified reference materials, but the specifics are not detailed in this summary.
§ 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.