(67 days)
Immunoassay for the in vitro quantitative determination of Prostate-Specific Antigen in human serum and plasma. The Elecsys PSA assay is further indicated for serial measurement of PSA to aid in the management of cancer patients.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.
The Elecsys® test principle is based on sandwich principle. Total duration of assay: 18 minutes (37° C).
• 1st incubation (9 minutes): Sample (20 µL), a biotinylated monoclonal PSA-specific antibody (70 µL), and a monoclonal PSA-specific antibody labeled with a ruthenium complex (70 µL) react to form a sandwich complex.
• 2nd incubation (9 minutes): After addition of streptavidin-coated microparticles (40 µL), the entire complex is 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 (0.4 second read frame).
•Results are determined via a calibration curve which is instrument-generated by 2-point calibration and a master curve provided via the reagent bar code.
Here's an analysis of the provided text regarding the Elecsys® PSA assay, structured to address your specific questions.
It's important to note that this document is a 510(k) summary for a diagnostic assay (a lab test), not a medical imaging device or an AI-powered system in the modern sense. Therefore, some of your questions, particularly those related to imaging, AI performance, human readers, and ground truth establishment for AI, are not directly applicable or addressable by this type of submission. This summary focuses on the analytical performance of the assay itself compared to a predicate assay.
Acceptance Criteria and Study Details for Elecsys® PSA Assay
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state "acceptance criteria" for each performance characteristic in a formalized table. Instead, it presents performance data for the new device (Elecsys PSA, 2nd Gen) and the predicate device (Elecsys PSA, 1st Gen) side-by-side, implying that the new device's performance should be comparable or improved relative to the predicate to establish substantial equivalence.
Based on the "Performance Characteristics" section, here's a table summarizing the reported device performance and implicitly accepted levels (by showing equivalence to the predicate):
| Feature | Elecsys PSA, 2nd Gen. Performance | Implicit Acceptance Criteria (based on Predicate) |
|---|---|---|
| Precision | (Comparable to Elecsys PSA, 1st Gen.) | |
| HS1 | Within-Run %CV: 1.8 | Within-Run %CV: 1.5 |
| Total %CV: 2.4 | Total %CV: 2.9 | |
| HS2 | Within-Run %CV: 2.5 | Within-Run %CV: 1.8 |
| Total %CV: 2.9 | Total %CV: 2.3 | |
| HS3 | Within-Run %CV: 2.2 | Within-Run %CV: 1.6 |
| Total %CV: 3.8 | Total %CV: 2.3 | |
| PC-TM1 | Within-Run %CV: 2.5 | Within-Run %CV: 1.1 |
| Total %CV: 2.7 | Total %CV: 2.1 | |
| PC-TM2 | Within-Run %CV: 2.3 | Within-Run %CV: 1.2 |
| Total %CV: 2.9 | Total %CV: 2.2 | |
| Sensitivity | (Comparable to Elecsys PSA, 1st Gen.) | |
| Analytical | 0.002 ng/mL | 0.002 ng/mL |
| Functional | 0.03 ng/mL | 0.03 ng/mL |
| Linearity | 0.002 - 100 ng/mL (±10% deviation) | 0.002 - 100 ng/mL (±10% deviation) |
| Method Comparison | y=1.0098x + 0.734 (r=0.998, N=108) (Least Squares) | (Implicitly, strong correlation with predicate) |
| y=1.0335x + 0.219 (r=0.998, N=108) (Passing Bablok) | (Implicitly, strong correlation with predicate) | |
| Hook Effect | No Hook Effect up to 17,000 ng/ml PSA | No Hook Effect up to 15,000 ng/ml PSA |
2. Sample Size Used for the Test Set and Data Provenance
- Precision: For each level (HS1, HS2, HS3, PC-TM1, PC-TM2), the sample size (N) was 60. The submission does not specify the country of origin or whether the data was retrospective or prospective. Given the nature of a lab assay performance study, these are typically prospective laboratory testing results.
- Method Comparison: The sample size (N) for the method comparison study was 108. No information on data provenance (country, retrospective/prospective) is provided.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This question is not applicable to this submission. For an in vitro diagnostic (IVD) assay like Elecsys® PSA, "ground truth" for the test set is established by the reference measurement procedure (i.e., the predicate device or a recognized reference method) or by the known concentrations of calibrators/controls used for analytical performance studies like precision and linearity. There are no "experts" in the sense of human readers/adjudicators for interpreting results in this context; performance is based on analytical measurements.
4. Adjudication Method for the Test Set
Not applicable. Adjudication methods like 2+1 or 3+1 refer to human expert consensus for interpreting images or clinical data, which is not relevant for an analytical assay.
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
Not applicable. This is an in vitro diagnostic assay, not an AI-powered medical imaging or decision support system that involves human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Not applicable in the usual sense of an "algorithm" as an AI. This is an automated immunoassay system. The "standalone" performance is what is presented in the Precision, Sensitivity, Linearity, and Hook Effect sections, as it describes the analytical performance of the instrument/reagent system without human interpretation beyond pipetting and loading. The "algorithm" here refers to the instrument's calibration and calculation of results from the chemiluminescent signal.
7. The Type of Ground Truth Used
For the Elecsys® PSA assay, the "ground truth" for the performance studies would be:
- For Precision: The known target concentrations of the quality control samples (HS1, HS2, HS3, PC-TM1, PC-TM2).
- For Sensitivity/Linearity: The gravimetrically or otherwise accurately prepared concentrations of PSA in dilution series.
- For Method Comparison: The results obtained from the predicate device (Elecsys PSA, 1st Gen) on the same samples.
- For Hook Effect: Samples with extremely high, known concentrations of PSA.
8. The Sample Size for the Training Set
Not applicable in the context of machine learning. This is an IVD assay, not an AI algorithm that undergoes a "training phase" on a dataset. The assay involves chemical reactions and signal detection, with a calibration curve set up using internal calibrators.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As explained above, there isn't a "training set" in the AI sense. Calibration curves, which are analogous to a "trained model" for converting signal to concentration, are established using known concentrations of PSA calibrators provided with the reagent kit.
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510(k) Summary
Elecsys® PSA on Elecsys 2010
の 2007年の1000年の1000年の1000年には、1000年には、1000年には、1000年には、1000年には、1000年には、1000年には、1000年には、1000年には1000年に100000000000000000000000000000000000000000000000000000000000000000000000000
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. |
|---|---|
| 1.Submittername, address,contact | Boehringer Mannheim Corporation9115 Hague RoadIndianapolis, In 46250(317) 845-3723 |
| Contact Person: Priscilla A. Hamill | |
| Date Prepared: August 14, 1998 | |
| 2.Device name | Proprietary name: Elecsys® PSA AssayCommon name: Electrochemiluminescence assay for the determination ofProstate-Specific Antigen (PSA). |
| Classification name: System, Test , Prostate-Specific antigen | |
| 3.Predicatedevice | We claim substantial equivalence to the Elecsys® PSA 1st Gen.(K964351/S1). |
| 4.DeviceDescription | The Elecsys® test principle is based on sandwich principle. Total duration ofassay: 18 minutes (37° C).• 1st incubation (9 minutes): Sample (20 µL), a biotinylated monoclonal PSA-specific antibody (70 µL), and a monoclonal PSA-specific antibody labeledwith a ruthenium complex (70 µL) react to form a sandwich complex.• 2nd incubation (9 minutes): After addition of streptavidin-coatedmicroparticles (40 µL), the entire complex is bound to the solid phase viainteraction of biotin and streptavidin. |
| 4.DeviceDescription(con't) | ·The reaction mixture is aspirated into the measuring cell where themicroparticles are magnetically captured onto the surface of the electrode.Unbound substances are then removed with ProCell. Application of a voltageto the electrode then induces chemiluminescent emission which is measuredby a photomultiplier (0.4 second read frame).•Results are determined via a calibration curve which is instrument-generatedby 2-point calibration and a master curve provided via the reagent bar code. |
| 5.Intended use | Immunoassay for the in vitro quantitative determination of Prostate-SpecificAntigen in human serum and plasma. The Elecsys PSA assay is furtherindicated for serial measurement of PSA to aid in the management of cancerpatients.The electrochemiluminescence immunoassay "ECLIA" is intended for use on theBoehringer Mannheim Elecsys 2010 immunoassay analyzer |
| 6.Comparison topredicatedevice | The Boehringer Mannheim, a Roche Diagnostics Company Elecsys® PSA, 1stGen. is cleared for use on the Elecsys 2010 immunoassay analyzer(K964351/S1). The application of the Elecsys® PSA, 2nd Gen. Assay on theElecsys 2010 immunoassay analyzer is substantially equivalent to the ElecsysPSA, 1st Gen. assay. |
Continued on next page
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The following table compares the Elecsys® PSA, 2nd Gen. with the predicate device, Elecsys® PSA, 1st Gen. Specific data on the performance of this test for Elecsys 2010 and Elecsys 1010, 2nd Gen. (separate premarket notification) have been incorporated into the draft labeling in attachment 5.
Similarities:
·Intended Use: Immunoassay for the in vitro quantitative determination of prostate-specific antigen. The assay is further indicated for serial measurement of PSA to aid in the management of cancer patients.
•Assay range: 0-100 ng/ml
· Assay methodology: Sandwich immunoassay
· Cross-Reactivity: None to PAP and ACT
·Specificity: Equimolar recognition of PSA-ACT and free PSA
· Application to Elecsys 1010 and 2010 immunoassay analyzers
·Reaction temperature and incubation times
·Performance specifications
Differences:
·Capture antibody
·Sample and reagent volumes
Continued on next page
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| Feature | Elecsys PSA, 2nd Gen. | Elecsys PSA, 1st Gen. | ||||
|---|---|---|---|---|---|---|
| Precision | Modified NCCLS (ng/mL): | Modified NCCLS (ng/mL): | ||||
| Level | HS1 | HS2 | HS3 | HS1 | HS2 | HS3 |
| N | 60 | 60 | 60 | 60 | 60 | 60 |
| Mean | 0.30 | 4.76 | 51.1 | 0.29 | 13.9 | 48.5 |
| Within-Run %CV | 1.8 | 2.5 | 2.2 | 1.5 | 1.8 | 1.6 |
| Total %CV | 2.4 | 2.9 | 3.8 | 2.9 | 2.3 | 2.3 |
| Modified NCCLS (ng/mL): | Modified NCCLS (ng/mL): | |||||
| PC-TM1 | PC-TM2 | PC-TM1 | PC-TM2 | |||
| N | 60 | 60 | 60 | 60 | ||
| Mean | 2.33 | 17.2 | 1.88 | 14.0 | ||
| Within-Run %CV | 2.5 | 2.3 | 1.1 | 1.2 | ||
| Total %CV | 2.7 | 2.9 | 2.1 | 2.2 |
Performance Characteristics:
Continued on next page
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F.
Substantial
equivalence, cont.
Performance Characteristics:
| Feature | Elecsys PSA, 2nd Gen. | Elecsys PSA, 1st Gen. |
|---|---|---|
| SensitivityAnalyticalFunctional | 0.002 ng/mL0.03 ng/mL | 0.002 ng/mL0.03 ng/mL |
| Linearity | 0.002 - 100 ng/mL (with adeviation from a linear lineof ±10%) | 0.002 - 100 ng/mL (with adeviation from a linear line of±10%) |
| MethodComparison | Vs Elecsys PSA, 1st Gen. (on2010) | |
| Least Squares$y=1.0098x + 0.734$r=0.998N=108 | ||
| Passing Bablok$y=1.0335x + 0.219$r=0.998N=108 | ||
| Hook Effect | No Hook Effect up to17,000 ng/ml PSA | No Hook Effect up to15,000 ng/ml PSA |
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Image /page/5/Picture/2 description: The image is a black and white seal for the Department of Health & Human Services - USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the seal is an abstract image of three human profiles facing to the right, with three curved lines below them.
OCT 2 7 1998 Ms. Priscilla A. Hamill Regulatory Affairs Consultant Roche Diagnostics, Boehringer Mannheim Corporation 9115 Haque Road Indianapolis, Tennessee 46250
Re : K982949 Elecsys® PSA Assay Trade Name: Requlatory Class: II Product Code: LTJ Dated: Auqust 14, 1998 Received: August 21, 1998
Dear Ms. Hamill:
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 leqally 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 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 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 requlatory 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.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
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Page 2
This letter will allow you to beqin 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 requlation (21 CFR Part 801 and additionally 809.10 for in vitro diaqnostic 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, "Misbrandinq 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/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Toutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radioloqical Health
Enclosure
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510(k) Number (if known): N/A
Device Name: Elecsys® PSA Assay
Indications For Use:
Immunoassay for the in vitro quantitative determination of prostate-specific antigen (PSA) in human serum and plasma. The Elecsys PSA assay is further indicated for serial measurement of PSA to aid in the management of cancer patients.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 2010 immunoassay analyzer.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
| Concurrence of CDRH, Office of Device Evaluation (ODE) | |
|---|---|
| Prescription Use(Per 21 CFR 801.109) | OR Over-The-Counter Use |
Cater E. Mokerin
(Optional Format 1-2-96)
(Division Sign-Off)
Division of Clinical Laboratory Devices KG83749
510(k) Number
§ 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.