(167 days)
The Bayer ADVIA® IMS PSA assay is an in vitro diagnostic device intended to quantitatively measure prostate specific antigen (PSA) in human serum. This assay is indicated for the measurement of serum PSA as an aid in management (monitoring) of prostate cancer patients. PSA values obtained using the Bayer ADVIA IMS assay method must be interpreted in conjunction with all other available clinical and laboratory data before a medical decision is determined.
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The provided text describes the acceptance criteria and the study for the Bayer ADVIA® IMS PSA assay.
Here's the information extracted and organized as requested:
Acceptance Criteria and Device Performance for Bayer ADVIA® IMS PSA Assay
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state pre-defined acceptance criteria in a table format, but rather reports performance characteristics. Based on the data presented and common analytical testing standards, the implicit acceptance criteria are inferred to be comparable or superior to the predicate device (Immuno 1 PSA Assay).
| Performance Characteristic | Implicit Acceptance Criteria (Inferred) | Reported Device Performance (ADVIA IMS) |
|---|---|---|
| Imprecision (Total CV%) | Comparable to or better than predicate device Immuno 1. Generally, lower CV% is better. | Level 2.6 ng/mL: 2.7% Level 6.5 ng/mL: 1.8% Level 24.1 ng/mL: 1.7% Level 99.1 ng/mL: 2.0% (Predicate Immuno 1: Level 3 ng/mL: 3.1%, Level 23 ng/mL: 3.4%, Level 96 ng/mL: 2.5%) |
| Correlation (R-value) | R-value close to 1 (indicating strong linear correlation with predicate). | Serum (N=54): R = 0.999 Serum (N=44): R = 0.999 |
| Regression Slope | Close to 1.0 (indicating similar proportionality to predicate). | Serum (N=54): 0.97 Serum (N=44): 0.97 95% Confidence Interval (Slope): 0.951 - 0.981 |
| Regression Intercept | Close to 0.0 (indicating similar bias to predicate). | Serum (N=54): -0.18 Serum (N=44): -0.06 95% Confidence Interval (Intercept): -0.49 - 0.37 |
| Sy.x (Std Error of Est.) | Low value, indicating low variability around the regression line. | Serum (N=54): 0.93 ng/mL Serum (N=44): 0.78 ng/mL 95% Confidence Interval (Sy.x): 0.53 - 1.27 |
| Interfering Substances (Effect %) | Recovery bias found to be of no clinical significance. | Hemoglobin: 2.8% Lipids (Triglycerides): 0.1% Bilirubin: 0.7% Immunoglobulin (IgG): -5.3% Albumin: -1.3% Cross-reactants (PAP, Kallikrein): 0.013%-0.018% Various Drugs: -1.8% to +2.4% (All reported as "of no clinical significance") |
| Recovery (%) | Recovery within a specified acceptable range (e.g., 90-110%). | Overall Mean Recovery: Sample #1: 99%, Sample #2: 101%, Sample #3: 100%, Sample #4: 101% (Individual dilution recoveries ranged from 97% to 104%). |
| Analytical Range | Clearly defined and clinically appropriate range. | 0.01 – 100 ng/mL |
| Minimum Detectable Concentration (ng/mL) | Comparable to or better than predicate device. | ADVIA IMS: 0.01 ng/mL (Predicate Immuno 1: 0.03 ng/mL) |
2. Sample sizes used for the test set and the data provenance
-
Correlation Studies (Test Set):
- N=54 serum samples (0.37-79.70 ng/mL)
- N=44 serum samples (0.07-62.93 ng/mL)
-
Imprecision Study: Six calibrator levels and commercial controls were tested. The exact number of individual samples (replicates for each level) is not specified but implied to be sufficient for robust CV calculation.
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Interfering Substances Study: Serum pool with PSA concentration of 4.0 ng/mL was spiked. Specific number of samples beyond "serum pool" is not detailed.
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Recovery Study: Four samples were used, each with several dilutions (5 dilution points per sample).
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Data Provenance: Not explicitly stated (e.g., country of origin, specific clinical sites). The study type is retrospective as it involves analyzing existing serum samples and comparing the new assay results to those obtained from a predicate device.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This type of in vitro diagnostic device (immunoassay) does not typically involve human expert interpretation for establishing ground truth in the same way as imaging or pathology studies. The "ground truth" for the test set is established by the measurements from the predicate device (Immuno 1 PSA Assay), which is itself a legally marketed and presumably validated diagnostic tool. Therefore:
- Number of experts: Not applicable in the context of interpretation.
- Qualifications of experts: Not applicable.
4. Adjudication method for the test set
Not applicable. The ground truth for comparative studies of quantitative assays is typically the result from the established predicate method, not a consensus of human interpretations.
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
Not applicable. This is an in vitro diagnostic assay, not an imaging or AI-assisted diagnostic tool that involves human readers interpreting cases.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, the studies presented (Imprecision, Correlation, Interfering Substances, Recovery, Analytical Range, Minimum Detectable Concentration) are all standalone performance evaluations of the ADVIA IMS PSA assay system. There is no human intervention in the measurement process once the sample is loaded and the assay runs. The results are quantitative values generated directly by the device.
7. The type of ground truth used
The primary ground truth used for performance validation is:
- Predicate Device Measurements: For correlation studies, the results obtained from the Immuno 1 PSA Assay on the same samples serve as the comparison (reference) "ground truth" for the new ADVIA IMS assay.
- Known Concentrations/Spikes: For imprecision, recovery, and interfering substance studies, known concentrations of PSA or spiked substances are used as the "ground truth" against which the device's measurements are evaluated.
8. The sample size for the training set
This document does not describe a "training set" in the context of machine learning or AI models. For an immunoassay, the concept of a training set is not directly applicable. The assay is developed and optimized during its R&D phase, and the studies presented here are for validation.
9. How the ground truth for the training set was established
Not applicable, as there is no mention of a training set for an AI model in this document. The "ground truth" for developing an immunoassay would be established through a combination of chemical principles, antibody specificity, detection methods, and extensive optimization using known calibrators and reference materials.
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DEC 1 7 2002
510(k) SUMMARY OF SAFETY AND EFFECTIVENESS PSA Assay for Bayer ADVIA® Integrated Modular System (IMS)TM
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.
X 02217 The assigned 510(k) number is:
1. Intended Use
The Bayer ADVIA® IMS PSA assay is an in vitro diagnostic device intended to quantitatively measure prostate specific antigen (PSA) in human serum. This assay is indicated for the measurement of serum PSA as an aid in management (monitoring) of prostate cancer patients. PSA values obtained using the Bayer ADVIA IMS assay method must be interpreted in conjunction with all other available clinical and laboratory data before a medical decision is determined.
2. Predicate Device
| Product Name | Reagent Part # | Calibrator Part # |
|---|---|---|
| Immuno 1 PSA Assay | T01-3450-51 | T03-3541-01 |
3. Device / Method
| Product Name | Reagent Part # / BANNumber | Calibrator Part # /BAN Number |
|---|---|---|
| ADVIA IMS PSA Assay | B42-3912-42 /02598475 (100 tests)06694045 (250 tests) | B43-3940-01/03625840 |
Imprecision
Within-run and total imprecision were evaluated by testing six calibrator levels and commercial controls. % CV was calculated based on all replicates using one calibration curve.
| ADVIA IMS | Immuno 1 | ||
|---|---|---|---|
| Level (ng/mL) | Total CV(%) | Level (ng/mL) | Total CV(%) |
| 2.6 | 2.7 | 3 | 3.1 |
| 6.5 | 1.8 | 23 | 3.4 |
| 24.1 | 1.7 | 96 | 2.5 |
| 99.1 | 2.0 |
Correlation (Y= ADVIA IMS, X = comparison system)
Correlation study was performed with forty four (44) serum samples (0.07 to 62.93 ng/mL).
| Specimen type | Comparison System (X) | N | Regression Equation | Syx (ng/mL) | R | Sample Range (ng/mL) |
|---|---|---|---|---|---|---|
| Serum | Immuno 1 | 54 | $0.97 * X - 0.18$ | 0.93 | 0.999 | 0.37-79.70 |
| Serum | Immuno 1 | 44 | $0.97 * X - 0.06$ | 0.78 | 0.999 | 0.07-62.93 |
| 95% Confidence Intervals | ||||||
| µg/L | Ng/mL | µg/L | ng/mL | |||
| Slope | 0.951 | 0.951 | 0.981 | 0.981 | ||
| Intercept | -0.49 | -0.49 | 0.37 | 0.37 | ||
| Sy.x | 0.53 | 0.53 | 1.27 | 1.27 |
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Serial Monitoring
Two examples of serial patient monitoring studies using Bayer ADVIA IMS assay results in comparison to results obtained for another marketed device are shown in the following figures.
Image /page/1/Figure/2 description: The image shows two line graphs comparing PSA levels over time for two patients. The first graph, titled "Longitudinal Sample - Patient 1", plots PSA levels from approximately 50 to 90 between July 2001 and December 2002. The second graph, titled "Longitudinal Sample - Patient 2", plots PSA levels from approximately 10 to 80 between July 2001 and September 2002. Both graphs compare "ADVIA IMS" and "Immuno 1" measurements.
Interfering Substances
Serum pool with PSA concentration of 4.0 ng/mL was spiked with hemoglobin, triglyceride, billirubin, albumin, immunoglobulins, PAP, kallikrein, and drug pools (up to two times lethal dose) and then assayed for PSA. In all cases the observed recovery bias was found to be of no clinical significance.
| InterferingSubstance | Interfering SubstanceConcentration | AnalyteConcentration | Effect | ||
|---|---|---|---|---|---|
| SI Units | (mg/dL) | (µg/L) | (ng/mL) | (%) | |
| Hemoglobin | 10.0 g/L | 1000 | 2.08 | 2.08 | 2.8 |
| Lipids(Triglycerides) | 11.3 mmol/L | 1000 | 3.57 | 3.57 | 0.1 |
| Bilirubin | 428 µmol/L | 25 | 4.05 | 4.05 | 0.7 |
| Immunoglobulin (IgG) | 60.0 g/L | 6000 | 3.13 | 3.13 | -5.3 |
| Albumin | 65.0 g/L | 6500 | 3.05 | 3.05 | -1.3 |
| Cross-Reactivities | |||||
| Cross-Reactant | Cross-ReactantConcentration | AnalyteConcentration | Cross-Reactivity | ||
| (µg/mL) | (µg/L) | (ng/mL) | (%) | ||
| PAP | 1.0 | 3.99 | 3.99 | 0.015 | |
| Kallikrein (plasma) | 1.0 | 4.23 | 4.23 | 0.018 | |
| Kallikrin (urine) | 1.0 | 3.86 | 3.86 | 0.013 | |
| Vincristine Sulfate | 13.5 | 3.82 | 3.82 | 0.3 | |
| Vinblastine | 5.11 | 3.82 | 3.82 | 0.3 | |
| Mitomycin C | 73 | 3.86 | 3.86 | 1.2 | |
| Tamoxifen - Free | 60 | 3.82 | 3.82 | 0.3 | |
| Tamoxifen - Citrate | 60 | 3.82 | 3.82 | 0.3 |
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| 5-Fluorouracil | 1600 | 3.65 | 3.65 | -1.8 |
|---|---|---|---|---|
| CyclophosphamideMonohydrate | 800 | 3.86 | 3.86 | 1.2 |
| Doxorubicin HCl | 51.8 | 3.86 | 3.86 | 1.2 |
| Diethylstibestrol | 23 | 3.82 | 3.82 | 0.3 |
| Methotrexate | 450 | 3.67 | 3.67 | -0.9 |
| Cis-Platinum | 173 | 3.82 | 3.82 | 0.3 |
| Lupron | 15 | 3.59 | 3.59 | 2.4 |
| Megestrol Acetate | 243 | 3.86 | 3.86 | 1.2 |
Recovery
Recovery of the PSA dilution in the range of 0.01 to 4.0 ng/mL was evaluated. Recovery ranged from 97 to 104%.
| Sample #1 | ||
|---|---|---|
| Expected , ng/mL | Observed, ng/mL | Recovery, % |
| 4.31 | 4.31 | 100 |
| 3.28 | 3.17 | 97 |
| 2.26 | 2.23 | 99 |
| 1.23 | 1.21 | 99 |
| 0.20 | 0.20 | 100 |
| Mean | 99 | |
| Sample #2 | ||
| Expected , ng/mL | Observed, ng/mL | Recovery, % |
| 4.27 | 4.27 | 100 |
| 3.25 | 3.35 | 103 |
| 2.23 | 2.24 | 100 |
| 1.21 | 1.21 | 100 |
| 0.19 | 0.19 | 100 |
| Mean | 101 | |
| Sample #3 | ||
| Expected , ng/mL | Observed, ng/mL | Recovery, % |
| 4.58 | 4.58 | 100 |
| 3.44 | 3.41 | 99 |
| 2.30 | 2.28 | 99 |
| 1.16 | 1.19 | 103 |
| 0.02 | 0.02 | 100 |
| Mean | 100 |
| Sample # 4 | ||
|---|---|---|
| Expected, ng/mL | Observed, ng/mL | Recovery, % |
| 4.38 | 4.38 | 100 |
| 3.30 | 3.25 | 98 |
| 2.22 | 2.24 | 101 |
| 1.14 | 1.19 | 104 |
| 0.06 | 0.06 | 100 |
| Mean | 101 |
Analytical Range
0.01 – 100 ng/mL
0.01-100 ng/ml
Minimum Detectable Concentration
| ADVIA IMS(ng/mL) | Immuno 1(ng/mL) |
|---|---|
| 0.01 | 0.03 |
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4. Conclusion
Performance of the ADVIA IMS PSA Assay on a Bayer ADVIA® IMS™ is equivalent to the specifications. No safety and effectiveness issues have been raised
12/04/02
Date
י
K. Edds Director Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of three human profiles facing right, arranged in a stacked formation. The profiles are rendered in black and have a flowing, abstract design. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the left side of the profile graphic.
Food and Drug Administration 2098 Gaither Road Rockville MD_20850
Kenneth T. Edds, Ph.D. Regulatory Affairs Manager Bayer Diagnostics 511 Benedict Avenue Tarrytown, NY 10591
Re:
K022177. Trade/Device Name: PSA (Prostate Specific Antigen) Assay for the ADVIA® IMS™ Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-associated antigen immunological test system Regulatory Class: Class II Product Code: LTJ; JIS Dated: December 5, 2002 Received: December 6, 2002
Dear Dr. Edds:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and 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) that do not require approval of a premarket approval application (PMA). 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 (PMA). it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act s requirements. including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer 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 Sutman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Kozal 77 510(k) Number:
Device Name: PSA (Prostate Specific Antigen) Assay for the ADVIA® IMS™
Indications for Use:
The Bayer ADVIA® IMS PSA assay is an in vitro diagnostic device intended to quantitatively measure prostate specific antigen (PSA) in human serum. This assay is indicated for the measurement of serum PSA as an aid in management (monitoring) of prostate cancer patients. PSA values obtained using the Baver ADVIA IMS assay method must be interpreted in conjunction with all other available clinical and laboratory data before a medical decision is determined.
(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-CounterUse
(Optional Format 1-2-96)
Hecord for H. Bantista
(Division Sion-Off) Division of Chrical Laboratory Device 510jk) 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.