(193 days)
The Vitros® CA 125 II is an in vitro assay intended for the quantitative measurement of OC 125 defined antigen in the serum or plasma (EDTA or heparin). The Vitros CA 125 II assay is to be used as an aid in monitoring response to therapy for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay values should be used in conjuction with other clinical methods used for monitoring ovarian cancer.
The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system. The system is comprised of three main elements: 1. The VITROS Immunodiagnostic Products (in this case VITROS Immunodiagnostic Products CA 125 II Reagent Pack, VITROS Immunodiagnostic Products CA 125 II Calibrators, which are combined by the VITROS Immunodiagnostic System to perform the VITROS CA 125 II assay). 2. The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. 3. Common reagents used by the VITROS System in each assay. The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.
The provided text describes a 510(k) premarket notification for the VITROS CA 125 II assay, which is an in vitro diagnostic device. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device rather than conducting a de novo study with strict acceptance criteria and a detailed study design as might be seen for novel AI/ML software.
Therefore, many of the requested categories are not applicable or cannot be determined from the provided document, as the FDA 510(k) process for this type of device does not typically require the same level of detail regarding acceptance criteria linked to specific performance endpoints, or a standalone study as would be required for a novel AI device addressing diagnostic performance (e.g., sensitivity, specificity, AUC) against a clinical ground truth.
However, I can extract the information that is present and indicate where information is missing or not applicable based on the nature of the submission.
Acceptance Criteria and Device Performance for VITROS CA 125 II assay
The primary "acceptance criterion" for a 510(k) submission like this is substantial equivalence to a predicate device. For in vitro diagnostic assays, this typically involves demonstrating comparable analytical performance, including correlation, precision, and other assay characteristics.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criterion (Implicit for 510(k) Equivalence) | Reported Device Performance |
|---|---|
| Correlation with Predicate Device | VITROS CA 125 II assay = 0.963 x [Boehringer Mannheim Elecsys CA 125 II] + 0.654 (U/mL) |
| Coefficient of Correlation | 0.946 |
| Analytical Sensitivity | Tests performed, but specific values not reported in summary. |
| Specificity | Tests performed, but specific values not reported in summary. |
| Precision | Tests performed, but specific values not reported in summary. |
| Dilution | Tests performed, but specific values not reported in summary. |
| Expected Values | Tests performed, but specific values not reported in summary. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: Samples from "a variety of clinical categories" were used for comparison. The exact number of samples is not specified in this summary document.
- Data Provenance: The origin of the clinical samples (e.g., country) is not specified. The document implies these were clinical samples ("samples from a variety of clinical categories"). It does not specify if the data was retrospective or prospective.
3. Number of Experts Used to Establish Ground Truth and Qualifications of Experts
- Not Applicable. For an in vitro diagnostic assay demonstrating analytical equivalence with a predicate, the "ground truth" for the test set is typically established by the measurement of the analyte by the predicate device itself, and potentially by reference methods for analytical performance characteristics. Expert interpretation of images or clinical outcomes is not the primary ground truth method for this type of device.
4. Adjudication Method for the Test Set
- Not Applicable. See point 3. Performance is based on quantitative analytical results, not adjudicated interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
- No. This is an in vitro diagnostic (IVD) assay, not an AI/ML imaging or diagnostic software that typically involves human readers. Therefore, an MRMC study is not applicable.
6. If a Standalone (algorithm only without human-in-the-loop performance) Study was Done
- Yes, effectively. As an IVD assay, the device operates autonomously to measure CA 125 II antigen in serum or plasma. Its performance is evaluated independently of human interpretation of its measurement to establish analytical equivalence. While the results are used by clinicians, the "performance" of the assay itself is standalone.
7. The Type of Ground Truth Used
- Comparative Measurement against Predicate Device (Boehringer Mannheim Elecsys CA 125 II). For analytical correlation, the predicate device's measurements served as the reference. For other analytical characteristics (sensitivity, specificity, etc.), standard laboratory reference methods or purified analytes would typically be used, but the specifics are "Refer to the VITROS CA 125 II assay package insert."
8. The Sample Size for the Training Set
- Not Applicable/Not Specified. This is a traditional immunoassay, not an AI/ML model that requires a distinct "training set" in the machine learning sense. The assay development and calibration process would involve extensive experimentation and optimization, but it's not described as a "training set" like in AI/ML.
9. How the Ground Truth for the Training Set Was Established
- Not Applicable/Not Specified. See point 8. The "ground truth" for developing such an assay would relate to accurate measurement of the CA 125 analyte using established analytical chemistry principles and reference materials, rather than a "ground truth" of patient outcomes or expert consensus.
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MAY 1 4 1999
VITROS CA 125 II assay
ADMINISTRATIVE I
510(k) Summary 1.1
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92
The assigned 510(k) number is: K983875.
- Submitter name, address, contact
Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101 (716) 453-3790
Contact Person: Anne Zavertnik
Date 510(k) prepared: October 29, 1998
2. Device Name
Trade or Proprietary Name: VITROS Immunodiagnostic Products CA 125 II Calibrators VITROS Immunodiagnostic Products CA 125 II Reagent Pack
Common Name: CA 125 II assay
Classification Name: test for the in vitro quantitative determination of OC 125 defined antigen in serum or plasma.
3. Predicate Device
The VITROS Immunodiagnostic Products CA 125 II assay is substantially equivalent to the Boehringer Mannheim Elecsys CA 125 II (K972162).
4. Device Description
The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum and plasma. Coated microwells are used as the solid phase separation system.
The system is comprised of three main elements:
-
- The VITROS Immunodiagnostic Products (in this casc VITROS Immunodiagnostic Products CA 125 II Reagent Pack, VITROS Immunodiagnostic Products CA 125 II Calibrators, which are combined by the VITKOS Immunodiagnostic System to perform the VITROS CA 125 Il assay).
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VITROS CA 125 II assay
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- The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits. The VITROS Immunodiagnostic System was cleared for market by a separate 510(k) pre-market notification (K962919).
-
- Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 510(k) pre-market notification (K964310).
The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.
5. Device Intended Use
The Vitros® CA 125 II is an in vitro assay intended for the quantitative measurement of OC 125 defined antigen in the serum or plasma (EDTA or heparin). The Vitros CA 125 II assay is to be used as an aid in monitoring response to therapy for patients with epithelial overian cancer. Serial testing for patient CA 125 assay values should be used in conjuction with other clinical methods used for monitoring ovarian cancer.
6. Comparison to Predicate Device
The VITROS Immunodiagnostic Products CA 125 II assay is substantially equivalent to Boehringer Mannheim Elecsys CA 125 II (predicate device), which was cleared by FDA (K972162) for IVD use.
The relationship between the VITROS CA 125 II assay and the predicate device, determined by Bablock Passing regression, is
VITROS CA 125 II assay = 0.963 x [Boehringer Mannheim Elecsys CA 125 II] + 0.654 (U/mL), with a correlation coefficient of 0.946.
Comparisons of the VITROS CA 125 II assay and the predicate device were performed with samples from a variety of clinical categories.
In addition to the studies mentioned above, tests were performed to obtain analytical sensitivity, specificity, precision, dilution and expected values. Refer to the VITROS CA 125 II assay package insert for VITROS CA 125 11 assay results.
Table 1 lists the similarities and differences of the device characteristics between the VITROS CA 125 II assay with the predicate device:
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/2/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of an eagle with three lines forming its body and wings. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.
MAY 1 4 1999
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Anne Zavertnik Regulatory Affairs Associate Ortho-Clinical Diagnostics, Inc. 100 Indigo Creek Drive Rochester, New York 14626-5101
K983875 Re: Trade Name: VITROS Immunodiagnostic Products CA 125 II Calibrators VITROS Immunodiagnostic Products CA 125 II Reagent Pack Regulatory Class: II Product Code: LTK February 22, 1999 Dated: Received: February 24, 1999
Dear Ms. Zavertnik:
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 You may, the Federal Food, Drug, and Cosmetic Act (Act). 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 Requlation (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 In addition, FDA may publish further requlatory action. announcements concerning your device in the Federal Register. this response to your premarket notification Please note: 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/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Sutman
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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1.3 Indications For Use Statement Page 1 of 1 510(k) Number (if known): K983875 Device Name: VITROS Immunodiagnostic Products CA 125 II Reagent Pack VITROS Immunodiagnostic Products CA 125 II Calibrators The Vitros® CA 125 II is an in vitro assay intended for the Indications for Use: quantitative measurement of OC 125 defined antigen in the serum or plasma (EDTA or heparin). The Vitros CA 125 II assay is to be used as an aid in monitoring response to therapy for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay values should be used in conjuction with other clinical methods used for monitoring ovarian cancer.
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices
| 510(k) Number | K983875 |
|---|---|
| --------------- | --------- |
| Prescription Use(Per 21 CFR 801.109) | OR | Over-The-Counter Use(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.