(164 days)
The Qualisys PSA Immunoassay is a paramagnetic particle immunoassay for the in vitro quantitative determination of prostate-specific antigen (PSA) in human serum. The Qualisys PSA Immunoassay is further indicated for the serial measurement of PSA as an aid in the prognosis and management of patients with prostate cancer.
The Qualisys PSA Immunoassay is a two-site chemiluminescense assay. 1st incubation: 15 minutes at room temperature. Specimen, control or calibrator [100 µL] and PSA Antibody Solution [100 µL] react to form a sandwich complex. 2nd incubation: 2 minutes at room temperature. Streptavidin-coated paramagnetic particle solution [25 µL] is added to the reaction mixture. After the 2-minute incubation, the sandwich complex is bound to the solid-phase via the interaction of biotin and streptavidin. Removal of unbound materials: The paramagnetic particles are washed four times with wash buffer [1.0 mL/wash] to remove unbound materials. Re-suspension of paramagnetic particles: Deionized (DI) water [25 uL] is added to re-suspend the washed paramagnetic particles. Substrate addition and detection: Chemiluminogenic substrate [50 uL] is added to the solid-phase bound complex and results in "glow" chemiluminescence, which is measured using a luminometer (photomultiplier). Emission of light is quantified for 1 second, and is expressed in relative light units (RLU). The amount of bound labeled antibody in RLU's is directly proportional to the concentration of PSA in the sample. Results are determined using cubic spline immunoassay curve fitting.
The Qualisys PSA Immunoassay is a device designed for the in vitro quantitative determination of prostate-specific antigen (PSA) in human serum, specifically for the serial measurement of PSA to aid in the prognosis and management of patients with prostate cancer.
Here's an analysis of its acceptance criteria and the supporting study:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a go/no-go fashion. Instead, it presents performance characteristics for the Qualisys PSA Immunoassay and compares them to the predicate device, Abbott IMx® PSA. For the purpose of this response, the performance characteristics of the Qualisys PSA are considered the reported device performance, and the comparison to the predicate implies that similar or improved performance is an acceptance benchmark for substantial equivalence.
| Feature | Predicate Device (Abbott IMx® PSA) Performance | Qualisys PSA Immunoassay Reported Performance |
|---|---|---|
| Precision | ||
| Intra-assay: Low | 3.5% (at 4.6 ng/mL) | 3.4% (at 0.52 ng/mL) |
| Intra-assay: Med | 3.3% (at 15.6 ng/mL) | 1.7% (at 3.05 ng/mL) |
| Intra-assay: High | 3.1% (at 60.2 ng/mL) | 3.0% (at 23.06 ng/mL) |
| Inter-assay: Low | 4.7% (at 4.6 ng/mL) | 5.7% (at 0.52 ng/mL) |
| Inter-assay: Med | 4.5% (at 15.6 ng/mL) | 2.6% (at 3.05 ng/mL) |
| Inter-assay: High | 5.3% (at 60.2 ng/mL) | 3.7% (at 23.06 ng/mL) |
| Analytical Sensitivity | 0.1 ng PSA/mL | 0.003 ng PSA/mL |
| Functional Sensitivity | Not reported | 0.1 ng PSA/mL |
| Spike Recovery | 91 to 103% | 90 to 110% |
| Dilution Recovery | Not reported | 92 to 108% |
| Method Comparison | (Reference device for comparison) | y = 0.9955x + 0.5185 (r² = 0.9747) vs Abbott IMx® PSA |
| Interfering Substances | No interference up to specific concentrations | Similar or improved interference thresholds |
| High Dose Hook Effect | Not reported | No high dose hook effect up to 1250 ng/mL |
Note: The specific PSA concentrations for the Qualisys precision targets differ from the predicate, making direct percentage comparison difficult without further context on the clinical relevance of those specific concentrations. However, the percentages themselves are in a similar range, indicating comparable precision.
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison Study: The test set for the method comparison study consisted of n = 108 samples.
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective. Given the nature of a 510(k) submission, it's highly likely to be prospective study data collected to demonstrate device performance.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an immunoassay for quantitative determination of PSA levels, not an imaging or interpretive device that requires expert review for ground truth. The "ground truth" for the test set in this context refers to the actual PSA concentrations in the samples, which were implicitly determined by the predicate device (Abbott IMx® PSA) that the Qualisys device is being compared against, or by a reference method. The document does not mention experts establishing ground truth in the way described for interpretive medical devices.
4. Adjudication Method for the Test Set
Not applicable. As this is a quantitative immunoassay, there would be no subjective interpretation requiring an adjudication method. The method comparison involves comparing numerical results obtained by the test device against the predicate device.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. An MRMC study is relevant for interpretive tasks where multiple readers evaluate cases. This device is a quantitative immunoassay and does not involve human "readers" in the performance assessment in the context of an MRMC study.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the performance characteristics listed (precision, sensitivity, recovery, method comparison, interference, hook effect) are all standalone performance metrics of the Qualisys PSA Immunoassay device itself, independent of human interpretation or intervention beyond performing the assay procedure.
7. The Type of Ground Truth Used
The ground truth for the method comparison study was established by the Abbott IMx® PSA device. The predicate device's measurements served as the reference against which the Qualisys PSA Immunoassay's measurements were compared (y = 0.9955x + 0.5185, r² = 0.9747). For other performance characteristics like precision, sensitivity, and recovery, the "ground truth" refers to the known concentrations of analytes in control samples or spiked samples.
8. The Sample Size for the Training Set
The document does not provide information on a "training set" or sample sizes used for training. Immunoassays are typically developed and validated rather than "trained" in the machine learning sense. The performance characteristics described are related to the analytical validation of the device.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As noted above, immunoassays typically undergo analytical validation rather than machine learning training. Therefore, a "training set" and its associated ground truth establishment method are not relevant in this context.
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Image /page/0/Picture/1 description: The image shows a sequence of handwritten alphanumeric characters. The sequence starts with the letter 'K', followed by the numbers '990234'. The characters are written in a simple, slightly irregular style.
Image /page/0/Picture/2 description: The image shows the logo for Qualisys Diagnostics, Inc. The word "Qualisys" is in a large, bold font, with the "Q" being particularly large and stylized. Below "Qualisys" is the text "Diagnostics, Inc." in a smaller font. The logo is simple and professional.
510(k) Summary
Qualisys PSA Immunoassay
This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
| 1. | Submittername, address,contact | Qualisys Diagnostics, Incorporated16 Technology Drive, Suite 118Irvine, CA 92618 |
|---|---|---|
| Telephone: (949) 788-0633Fax: (949) 788-0623 | ||
| Contact Person: Grace Kwan | ||
| Date Prepared: May 19, 1999 | ||
| 2. | Device name | Proprietary name: Qualisys PSA Immunoassay |
| Common name: Chemiluminescense assay for the determination ofProstate-Specific Antigen (PSA). | ||
| Classification Name: Prostate-Specific Antigen (PSA) for Managementof Prostate Cancers | ||
| 3. | Predicatedevice | Abbott IMx® PSA(P910007) |
| 4. | Devicedescription | The Qualisys PSA Immunoassay is a two-site chemiluminescense assay. 1st incubation: 15 minutes at room temperature. Specimen, control or calibrator [100 µL] and PSA Antibody Solution [100 µL] react to form a sandwich complex. 2nd incubation: 2 minutes at room temperature. Streptavidin-coated paramagnetic particle solution [25 µL] is added to the reaction mixture. After the 2-minute incubation, the sandwich complex is bound to the solid-phase via the interaction of biotin and streptavidin. Removal of unbound materials: The paramagnetic particles are washed four times with wash buffer [1.0 mL/wash] to remove unbound materials. |
| 16 Technology Drive, Suite 118 • Irvine, CA 92618(949) 788-0633 • Fax (949) 788-0623Attachment 1Page 1 of 4 |
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Qualisys Diagnostics, Incorporated
| Devicedescription(continued) | Re-suspension of paramagnetic particles: Deionized (DI) water [25uL] is added to re-suspend the washed paramagnetic particles. | ||||
|---|---|---|---|---|---|
| Substrate addition and detection: Chemiluminogenic substrate [50 uL]is added to the solid-phase bound complex and results in "glow"chemiluminescence, which is measured using a luminometer(photomultiplier). Emission of light is quantified for 1 second, and isexpressed in relative light units (RLU). | |||||
| The amount of bound labeled antibody in RLU's is directlyproportional to the concentration of PSA in the sample. Results aredetermined using cubic spline immunoassay curve fitting. | |||||
| 5. | Intended use | The Qualisys PSA Immunoassay is a paramagnetic particle immunoassayintended for the in vitro quantitative determination of prostate-specificantigen (PSA) in human serum. The Qualisys PSA Immunoassay isfurther indicated for the serial measurement of PSA as an aid in theprognosis and management of patients with prostate cancer. | |||
| 6. | Comparison topredicatedevice | The Qualisys PSA Immunoassay is substantially equivalent to otherproducts in commercial distribution intended for similar use. Most notablyit is substantially equivalent to the currently marketed Abbott IMx® PSA.The following tables compare the Qualisys PSA Immunoassay with thepredicate device, Abbott IMx® PSA: | |||
| Similarities: | |||||
| Assay Methodology:● | Sandwich immunoassay | ||||
| Sample Type: | Serum | ||||
| Storage Condition: | 2-8 °C | ||||
| I abel | Alkaline Phosphatase |
- Photomultiplier Tube (PMT) Detector: .
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Qualisys Diagnostics, Incorporated
510(k) Summary (continued)
| Comparison to | Differences: | ||
|---|---|---|---|
| predicate(continued) | Feature | Qualisys PSA | Abbott IMx® PSA |
| Intended Use | For the in vitroquantitative determinationof PSA in human serum.It is further indicated forthe serial measurement ofPSA as an aid in theprognosis andmanagement of patientswith prostate cancer. | For the quantitativemeasurement of PSA inhuman serum: 1) as anaid in the detection ofprostate cancer whenused in conjunction withDRE in men aged 50years or older. Prostaticbiopsy is required fordiagnosis of cancer; 2) asan adjunctive test used asan aid in the managementof prostate cancerpatients. | |
| Sample Volume | 100 µL | 150 µL | |
| Assay Range | 0 to 50 ng/mL | 0 to 100 ng/mL | |
| Temp. Control | Not Required(Room Temperature) | Required | |
| InstrumentRequired | Zylux Luminometer | Abbott IMx® Analyzer | |
| Test Processing | Manual(A liquid handling systemmay be use to assist in thepipetting of multiplesamples.) | Automated | |
| Control Levels | 2 | 3 | |
| CalibrationLevels | 5 | 6 | |
| CaptureAntibody | Monoclonal | Polyclonal | |
| Solid-phase | Streptavidin-coatedparamagnetic particles | Monoclonal Anti-PSAcoated microparticles | |
| Substrate | ImmuGlow™ (Indoxyl -3-phosphate and lucigenin) | 4-MethylumbelliferylPhosphate | |
| Detection | Chemiluminescence | Fluorescence | |
| Data Analysis | External software: cubicspline for curve fitting anddata reduction | Internal data reductionvia microcomputer | |
| Calibration | Full calibration curve withevery run | Full calibration curveevery 4 weeks | |
| Comparison topredicatedevice(continued) | Performance Characteristics:Feature | Qualisys PSAng/mL PSA | Abbott IMx® PSAng/mL PSA |
| PrecisionIntra-assay | Low (0.52) 3.4%Med (3.05) 1.7%High (23.06) 3.0% | Low (4.6) 3.5%Med (15.6) 3.3%High (60.2) 3.1% | |
| Inter-assay | Low (0.52) 5.7%Med (3.05) 2.6%High (23.06) 3.7% | Low (4.6) 4.7%Med (15.6) 4.5%High (60.2) 5.3% | |
| AnalyticalSensitivity | 0.003 ng PSA/mL | 0.1 ng PSA/mL | |
| FunctionalSensitivity | 0.1 ng PSA/mL | Not reported | |
| Spike Recovery | 90 to 110% | 91 to 103% | |
| DilutionRecovery | 92 to 108% | Not reported | |
| MethodComparison | versus Abbott IMx® PSA:n = 108Range of values (Abbott): 0 to 46.83 ng PSA/mLRange of values (Qualisys): 0 to 42.30 ng PSA/mL$y = 0.9955x + 0.5185 (Least Squares)$$r^2$ = 0.9747$S^2_{slope}$ = 0.000243$S^2_{y-intercept}$ = 0.067012 | ||
| InterferingSubstances | No interference up to:Bilirubin 49 mg/dLHemoglobin 600 mg/dLIgG 1900 mg/dLPAP 1000 ng/mLProtein 13 g/dLTriglycerides 2730 mg/dLCyclophosphamide 700 µg/mLDES 2 µg/mLDoxorubicin HCI 16 µg/mLMethotrexate 30 µg/mLMegestrol Acetate 90 µg/mLFlutamide 10 µg/mLLupron 100µg/mL | No interference up to:25 mg/dL600 mg/dL250-2900 mg/dL1000 ng/mL3-13 g/dL3000 mg/dL700 µg/mL2 µg/mL16 µg/mL30 µg/mL90 µg/mL10 µg/mL100µg/mL | |
| High Dose HookEffect | No high dose hook effectup to 1250 ng/mL | Not reported |
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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of an eagle with three curved lines representing its wings.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
JUL - 9 1999
Ms. Grace Kwan Director, Ouality and Regulatory Affairs Qualisys Diagnostics, Inc. 16 Technology Drive, Suite 118 Irvine, California 92618
Re: K990234
Trade Name: Oualisys PSA Immunoassay Regulatory Class: II Product Code: LTJ Dated: May 19, 1999 Received: May 20, 1999
Dear Ms. Kwan:
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 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). 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 requirements, 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 (301) 443-6597, or at its internet address "http://www.fda.gov/cdrlv/dsma/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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Attachment 4
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Indications for Use Statement
| 510(k) Number | K990234 |
|---|---|
| Device Name | Qualisys PSA Immunoassay |
| Indications for Use | The Qualisys PSA Immunoassay is a paramagnetic particle immunoassay for the in vitro quantitative determination of prostate-specific antigen (PSA) in human serum. The Qualisys PSA Immunoassay is further indicated for the serial measurement of PSA as an aid in the prognosis and management of patients with prostate cancer. |
PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON ANOTHER PAGE IS NEEDED ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Concurrence of CDRH, Office of Device Evaluation (ODE)
| (Division Sign-Off) | |
|---|---|
| Division of Clinical Laboratory Devices | |
| 510(k) Number | K990234 |
| Prescription Use(Per 21 CFR 801.109) | ✓ | OR | Over-The-Counter 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.