(282 days)
Immunoassay for the in vitro determination of OC 125 reactive determinants. These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer, excluding those with cancer of low malignant potential. The Elecsys® CA 125II is indicated for use as an aid in the detection of residual or recurrent ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. The Elecsys CA 125II assay is further indicated for serial measurement of CA 125II to aid in the management of cancer patients.
The Elecsys® CA 125 IITM employs a sandwich test principle with monoclonal antibodies directed against CA 125 II and with streptavidin microparticles and electrochemiluminescence detection.
Total duration of assay: 18 minutes.
• 1st Incubation: 40 µl of sample a biotinylated monoclonal CA 125 II- specific antibody and a monoclonal CA 125 II-specific antibody labeled with a ruthenium complex react to form a sandwich complex.
• 2nd Incubation: after the addition of streptavidin-coated microparticles, the complex becomes 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.
• Results are determined via a calibration curve which is instrument- specifically generated by 2-point calibration and a master curve provided via the reagent bar code.
The provided text describes a 510(k) summary for the Elecsys® CA 125 IITM device, an immunoassay for the determination of OC 125 reactive determinants. While the document outlines the device description, intended use, and comparison to a predicate device, it does not explicitly state specific acceptance criteria or provide a detailed study that proves the device meets those criteria in a format that allows direct extraction of all requested information.
However, based on the information provided, we can infer some aspects of the performance evaluation and present what is available.
Here's an attempt to answer your questions based on the given text, acknowledging the limitations:
1. A table of acceptance criteria and the reported device performance
The document does not present a formal table of acceptance criteria with corresponding performance metrics. Instead, it lists studies performed as part of the comparison to the predicate device. The underlying acceptance for these studies would implicitly be substantial equivalence to the predicate device (CENTOCOR® CA 125 IITM RIA).
| Acceptance Criteria (Inferred from study types) | Reported Device Performance (Summary from text) |
|---|---|
| Assay Precision (NCCLS recommendations) | Evaluated according to NCCLS recommendations. (Specific metrics like %CV or SD are not provided in this summary.) |
| Lower Detection Limit | Determination of the lower detection limit. (Specific value is not provided.) |
| Linearity | Demonstration of linearity. (Specific range or r-squared value is not provided.) |
| Correlation with Predicate Device | Correlation with the predicate device. (Specific correlation coefficient or agreement percentage is not provided.) |
| Interference (Endogenous substances, drugs) | Evaluation of the effect of various endogenous substances (hemoglobin, biotin, triglyceride, bilirubin, and rheumatoid factor), and commonly used pharmaceutical compounds, and serum / plasma sample comparisons. (Specific impact or findings are not provided.) |
| Hook Effect | Determination of hook effect. (Specific findings are not provided.) |
| Stability | Stability studies. (Specific stability period or conditions are not provided.) |
| Clinical Correlation | Comparisons of the Elecsys CA 125 II and the predicate device were performed with samples from serially monitored patients diagnosed and treated for ovarian cancer. (Specific clinical outcomes or direct comparative stats are not provided, but implies similar performance given the "substantial equivalence" claim.) |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size for Test Set: Not explicitly stated. The text mentions "samples from serially monitored patients diagnosed and treated for ovarian cancer" for clinical correlation, but no number is given.
- Data Provenance: Not specified. It's unclear if the data was retrospective or prospective, or its country of origin.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This device is an immunoassay (laboratory test), not an imaging device requiring expert interpretation in the same way a radiologist would. Therefore, the concept of "experts" establishing ground truth for a test set in this context would typically refer to reference laboratory methods or established clinical diagnoses. The document does not provide details on how the ground truth was established for the comparison studies, nor does it mention specific experts or their qualifications for interpreting the test results in the "test set" (i.e., patient samples).
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable in the context of this immunoassay. Adjudication methods like 2+1 or 3+1 are typically used for subjective assessments or image interpretations where multiple human readers disagree. For an immunoassay, the "ground truth" (or reference method) is generally determined by a standardized lab procedure, not a consensus of human reviewers of the test result itself.
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
The device is an automated immunoassay. It does not involve human readers interpreting images or data that would be "assisted" by AI. Therefore, an MRMC study or AI assistance is not applicable to this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the Elecsys® CA 125 IITM is a standalone diagnostic device (an algorithm/automated system). Its performance described in the document is inherently "standalone" as it produces numerical results without direct human intervention in the result generation process itself, though clinical interpretation by a physician would follow.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The document implies clinical diagnostic information ("serially monitored patients diagnosed and treated for ovarian cancer") as the context for the comparison studies. For the analytical performance studies (precision, linearity, LLD), the ground truth would be based on known concentrations in control materials or reference measurements. For correlation with the predicate device, the "ground truth" for comparison is the results from the CENTOCOR® CA 125 IITM RIA.
8. The sample size for the training set
This document describes a 510(k) submission for a diagnostic immunoassay, not a machine learning or AI-based device. Therefore, the concept of a "training set" in the context of developing an algorithm is not applicable. The device is based on established immunochemical principles.
9. How the ground truth for the training set was established
As there is no "training set" in the AI/ML sense for this type of device, this question is not applicable. The calibration curve is instrument-specifically generated by 2-point calibration and a master curve provided via the reagent bar code. These calibration materials serve a similar function to "training" by setting the operational parameters for measurement.
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| MAR 18 1998 | 510(k) Summary |
|---|---|
| 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 Rd.Indianapolis, IN 46250(317) 845-2000 |
| Contact Person: LeeAnn Chambers, RACDate Prepared: June 5, 1997 | |
| 2) Device name | Proprietary name: Elecsys® CA 125 IITMCommon name: Epithelial Ovarian Tumor Associated Antigen |
| Classification name: Tumor Associated Antigen Immunological Test System | |
| 3) Predicatedevice | We claim substantial equivalence to CENTOCOR® CA 125 IITM RIA. |
| 4) DeviceDescription | The Elecsys® CA 125 IITM employs a sandwich test principle withmonoclonal antibodies directed against CA 125 II and with streptavidinmicroparticles and electrochemiluminescence detection. |
| Total duration of assay: 18 minutes.• 1st Incubation: 40 µl of sample a biotinylated monoclonal CA 125 II-specific antibody and a monoclonal CA 125 II-specific antibody labeledwith a ruthenium complex react to form a sandwich complex.• 2nd Incubation: after the addition of streptavidin-coated microparticles, thecomplex becomes bound to the solid phase via interaction of biotin andstreptavidin. | |
| 4) DeviceDescription | • 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 avoltage to the electrode then induces chemiluminescent emission which ismeasured by a photomultiplier.• Results are determined via a calibration curve which is instrument-specifically generated by 2-point calibration and a master curve providedvia the reagent bar code. |
| 5.Intended use | Immunoassay for the in vitro determination of OC 125 reactive determinants.These determinants are associated with a high molecular weight glycoproteinin serum and plasma of women with primary epithelial invasive ovariancancer, excluding those with cancer of low malignant potential. TheElecsys® CA 12511 is indicated for use as an aid in the detection of residual orrecurrent ovarian carcinoma in patients who have undergone first-line therapyand would be considered for diagnostic second-look procedures. The ElecsysCA 125II assay is further indicated for serial measurement of CA 125II to aidin the management of cancer patients. |
| 6) Comparisonto predicatedevice | The Boehringer Mannheim Elecsys CA 125 II is substantially equivalent toother products in commercial distribution intended for similar use. Mostnotably it is substantially equivalent to the currently marketed CENTOCORCA 125 II RIA.Studies performed include:• evaluation of assay precision according to NCCLS recommendations,• determination of the lower detection limit,• demonstration of linearity,• correlation with the predicate device,• evaluation of the effect of various endogenous substances (hemoglobin,biotin, triglyceride, bilirubin, and rheumatoid factor), and commonly usedpharmaceutical compounds, and serum / plasma sample comparisons,• determination of hook effect, and• stability studies. |
| In addition, comparisons of the Elecsys CA 125 II and the predicate devicewere performed with samples from serially monitored patients diagnosed andtreated for ovarian cancer. |
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510(k) Summary, Continued
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MAR 18 1998
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Ms. Patricia M. Klimley Manager, Regulatory Affairs Boehringer Mannheim Corp. Laboratory Diagnostics 4300 Hacienda Drive P.O. Box 9002 Pleasanton, CA 94566-0900
Re : K972162 Trade Name: Elecsys® CA 125 IITM Requlatory Class: II Product Codes: LTK Dated: December 17, 1997 Received: December 18, 1997
Dear Ms. Klimely:
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 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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, FDA will verify-such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, the Food and Druq Administration (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 requlations.
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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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours.
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiologica! Health
Enclosure
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510(k) Number (if known): Device Name: Elecsys CA 125 II Indications for Use:
Immunoassay for the in vitro determination of OC 125 reactive determinants. These determinants are associated with a high molecular weight glycoprotein in serum and plasma of women with primary epithelial invasive ovarian cancer, excluding those with cancer of low malignant potential. The Elecsys® CA 125II is indicated for use as an aid in the detection of residual or recurrent ovarian carcinoma in patients who have undergone first-line therapy and would be considered for diagnostic second-look procedures. The Elecsys CA 125II is further indicated for serial measurement of CA 125II to aid in the management of cancer patients
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Deborah M. Moore
for Dr. Peter Moskin
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K972162
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.