(132 days)
This in vitro immunoassay is intended to quantitavely measure CA 15-3 values in human serum. When used in conjunction with other clinical and diagnostics procedures, serial testing using ADVIA IMS CA 15-3 Assay on a Bayer ADVIA® IMS ™, is indicated for monitoring the course of disease and therapy in metastatic breast cancer patients, and for the detection of recurrence in previously treated Stage II, with greater than two positive lymph nodes, or Stage III breast cancer patients.
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The information provided describes the performance of the CA 15-3 Assay for the Bayer ADVIA® Integrated Modular System (IMS)™ as part of a 510(k) premarket notification. This submission focuses on demonstrating substantial equivalence to a predicate device, rather than a clinical study evaluating the device's impact on human readers or clinical outcomes.
Here's an analysis of the provided information, structured according to your request:
Acceptance Criteria and Device Performance
The provided document doesn't explicitly state "acceptance criteria" for each performance metric as a numerical threshold, but rather presents the device's performance characteristics with the implicit understanding that these values are considered acceptable for substantial equivalence to the predicate device. The conclusion explicitly states: "Performance of the ADVIA IMS CA 15-3 Assay on a a Bayer ADVIA® IMS ™ is equivalent to the performance of the CA 15-3 Assay on the predicate device (Immuno 1) and is within proposed specifications."
| Performance Characteristic | Acceptance Criteria (Implicit from Predicate & Equivalence) | Reported Device Performance (ADVIA IMS CA 15-3 Assay) |
|---|---|---|
| Imprecision | Comparable to predicate device (Immuno 1) | Level 1 (12.3 U/mL): 4.7% Total CV |
| Level 2 (29.6 U/mL): 5.5% Total CV | ||
| Level 3 (59.1 U/mL): 5.3% Total CV | ||
| Correlation (vs. Predicate Immuno 1) | Strong linear correlation with predicate device (e.g., R-value close to 1, Syx indicating low scatter) | N = 73 serum specimens |
| Regression Equation: $1.061 * X + 1.50$ (Y=ADVIA IMS, X=Immuno 1) | ||
| Syx (U/mL): 3.04 | ||
| R (Correlation Coefficient): 0.996 | ||
| Sample Range: 7.02 - 184.9 U/mL | ||
| Interfering Substances (Effect % change) | Minimal effect (generally < 10% or clinically insignificant) compared to predicate device. | Hemoglobin (1000 mg/dL): 1.1% change (at 16.2 U/mL CA 15-3) |
| Lipids - Triglycerides (1000 mg/dL): 2.5% change (at 27.4 U/mL CA 15-3) | ||
| Bilirubin (25 mg/dL): 0.1% change (at 35.5 U/mL CA 15-3) | ||
| IgG (6000 mg/dL): 2.3% change (at 31.5 U/mL CA 15-3) | ||
| Albumin (6000 mg/dL): 4.6% change (at 28.0 U/mL CA 15-3) | ||
| Analytical Range | Defined range of accurate measurement | 0.04 - 200 U/mL |
| Minimum Detectable Concentration | Low enough for intended use, comparable to predicate. | Not explicitly stated but section title appears in the document. The content related to it is unreadable due to OCR errors. |
Study Details:
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Sample size used for the test set and the data provenance:
- Imprecision: Not explicitly stated as a "test set" sample size but typically involves multiple replicates over several days with control materials. Not specified for the ADVIA IMS data.
- Correlation: 73 serum specimens.
- Data Provenance: Not explicitly stated. Given it's a 510(k) submission for a US market device, the data is typically generated in a controlled laboratory setting by the manufacturer, which could be in the US or internationally, but specific country of origin is not mentioned. The data is retrospective in the sense that samples were run and compared to the predicate, but specific retrospective/prospective collection of patient samples is not detailed.
- Interfering Substances: Specific sample sizes for each substance challenge are not provided, but typically involves a batch of samples spiked with interferents.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is an in vitro diagnostic (IVD) device, not an AI or imaging device that requires human expert review for "ground truth". The "ground truth" for this assay is the actual concentration of CA 15-3 in the specimen, as measured by a reference method or the predicate device that the new device is being compared against.
- Therefore, no human experts (e.g., radiologists) were used to establish ground truth in the context you're asking. The analytical performance is established by comparing the device's results to those from the predicate device or known concentrations of analytes in quality control materials.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable. This type of adjudication is used in studies where human interpretation of medical images or clinical data forms the ground truth, often with disagreement among reviewers. For an IVD assay, the comparison is quantitative and objective, typically against a reference measurement or predicate device, not subjective human interpretations.
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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:
- No. This is an IVD device for measuring a biomarker in blood, not an imaging or AI-assisted diagnostic tool. Therefore, an MRMC study and the concept of "human readers improving with AI assistance" are not relevant to this device or its submission.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Not applicable in the context of an AI algorithm. The device, by its nature as an automated immunoassay, operates in a "standalone" fashion where the instrument and reagents produce a quantitative result without direct human intervention in the result generation process itself (though human operators initiate and monitor the process). Its performance is evaluated independently of human interpretation of the raw signal; the numerical result is the output.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- For Imprecision, the ground truth is the "true" concentration of the control material, established by the manufacturer and often traceable to higher-order reference materials, or an average of multiple measurements.
- For Correlation, the "ground truth" for comparison is the measurement obtained from the predicate Immuno 1 system. This is a common approach for demonstrating substantial equivalence for IVDs.
- For Interfering Substances, the ground truth is the known concentration of CA 15-3 in the sample before the addition of the interfering substance.
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The sample size for the training set:
- This device, being an IVD immunoassay, does not have a "training set" in the context of machine learning or AI models. The development and calibration of such assays involve extensive R&D, reagent formulation, and analytical testing, but not a "training set" of data in the AI sense.
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How the ground truth for the training set was established:
- As there is no "training set" in the AI sense, this question is not applicable. The assay's performance characteristics are established through rigorous analytical verification and validation against known standards and comparison to a predicate device.
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NOV 12 2002
510(k) SUMMARY OF SAFETY AND EFFECTIVENESS CA 15-3 Assay for Bayer ADVIA® Integrated Modular System (IMS) ™
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.
The assigned 510(k) number is: (leave blank)
1. Intended Use
This in vitro immunoassay is intended to quantitavely measure CA 15-3 values in When used in conjunction with other clinical and diagnostics human serum. procedures, serial testing using ADVIA IMS CA 15-3 Assay on a Bayer ADVIA® IMS ™, is indicated for monitoring the course of disease and therapy in metastatic breast cancer patients, and for the detection of recurrence in previously treated Stage II, with greater than two positive lymph nodes, or Stage III breast cancer patients.
Predicate Device 2.
| Product Name | Reagent Part # | Calibrator Part # |
|---|---|---|
| Immuno 1 CA 15-3 | T01-3553-51 | T03-3554-01 |
3. Device / Method
| Product Name | Reagent Part # /BAN # | Calibrator Part # /BAN # |
|---|---|---|
| ADVIA IMS CA 15-3Assay | B42-3894-41 /08623765 | B43-3926-01 /05523158 |
A. Imprecision
| ADVIA IMS | |
|---|---|
| Level(U/mL) | TotalCV (%) |
| 12.3 | 4.7 |
| 29.6 | 5.5 |
| 59.1 | 5.3 |
| Immuno 1 | |
|---|---|
| Level(U/mL) | TotalCV(%) |
| 13.5 | 4.0 |
| 33.2 | 3.3 |
| 102.3 | 3.4 |
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| B. Correlation (T-ADVIA IMS, X-Comparison system) | ||||||
|---|---|---|---|---|---|---|
| Specimen type | Comparison System (X) | N | Regression Equation | Syx (U/mL) | R | Sample Range (U/mL) |
| Serum | Immuno 1 | 73 | $1.061 * X+1.50$ | 3.04 | 0.996 | 7.02-184.9 |
B. Correlation (Y=ADVIA IMS. X=Comparison system)
C. Interfering Substances
| InterferingSubstance | Interfering Sub.Conc. (mg/dL) | CA 15-3 Conc.(U/mL) | Effect(% change) |
|---|---|---|---|
| Hemoglobin | 1000 | 16.2 | 1.1 |
| Lipids(Triglycerides) | 1000 | 27.4 | 2.5 |
| Bilirubin | 25 | 35.5 | 0.1 |
| IgG | 6000 | 31.5 | 2.3 |
| Albumin | 6000 | 28.0 | 4.6 |
Analytical Range : 0.04 - 200 U/mL
Minimum Detectable Concentration
| A TREFF . | /TT' | |
|---|---|---|
| TMC /TIl- | mminn | |
| CC1------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | C11.00Section of the consisted to the considered to the contrôleant of the comments of the comments of the comments of the comments of the comments of the comments of the comments |
Conclusion 4.
Performance of the ADVIA IMS CA 15-3 Assay on a a Bayer ADVIA® IMS ™ is equivalent to the performance of the CA 15-3 Assay on the predicate device (Immuno 1) and is within proposed specifications. No safety and effectiveness issues have been raised.
Hume OPJ Taks
Kenneth T. Edds Manager Regulatory Affairs Bayer Corporation 511 Benedict Avenue, Tarrytown, NY 10591.
7/01/02
Date
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus, which is a symbol often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus. The logo is black and white.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 1 2 2002
Kenneth T. Edds, Ph.D. Regulatory Affairs Manager Bayer Diagnostics Corporation 511 Benedict Avenue Tarrytown, NY 10591-5097
Re: K022178
Trade/Device Name: CA15-3 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: MOI, JIT Dated: October 25, 2002 Received: October 29, 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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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 1 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" (21CFR 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 Butman
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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K022178 510(k) Number:
Device Name: CA15-3 Assay for the ADVIA® IMS™
Indications for Use:
The Bayer ADVIA® IMS™CA 15-3 Assay is an in vitro diagnostic device intended to quantitatively measure CA 15-3 Assay values in human serum. When used in conjunction with other clinical and diagnostic procedures, serial testing with CA 15-3 Assay results are useful in monitoring the course of disease and therapy in metastatic breast cancer patients, and for the detection of recurrence in previously treated Stage II, with greater than two positive lymph nodes, or Stage III breast cancer patients.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
| J.P. Reeves | |
|---|---|
| (Division Sign-Off) | |
| Division of Clinical Laboratory Devices | |
| 510(k) Number | K022178 |
| Prescription Use | |
|---|---|
| CounterUse | |
| (Per 21 CFR 801.109) | OR Over-The- |
(Optional Format 1-2-96)
§ 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.