(432 days)
The LOCI CA 125 II™ method is an in vitro diagnostic test for the quantitative measurement of CA 125 antigen in human serum and lithium heparin and EDTA plasma on the Dimension Vista® System. Measurements of CA 125 are used as an aid in monitoring disease progress or response to therapy or for the recurrent or residual disease for patients with epithelial ovarian cancer. Serial testing for patient CA 125 assay values should be used in conjunction with other clinical methods used for monitoring ovarian cancer. It is recommended that the LOCI CA 125 Il method be used in conjunction with signs and symptoms of a clinical evaluation by a physician trained and experienced in the management of gynecological cancers. This assay is not intended for screening or diagnosis of ovarian cancer or for use on any other system.
The LOCI 6 CAL is an in vitro diagnostic product for the calibration of Alpha-Fetoprotein (AFP), Carcinocmbryonic Antigen (CEA), and CA 125 (CA125) methods on the Dimension Vista® System.
The LOCI CA 125Il™ method is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI® technology. The LOCI® reagents include two synthetic bead reagents and a biotinylated anti-CA 125 monoclonal antibody (M11) fragment. The first bead reagent (Chemibeads) is coated with an anti-CA125 monoclonal antibody (OC 125) and contains a chemiluminescent dye. The use of the M11 antibody in combination with OC 125 defines this method as a second generation CA 125 assay. The second bead reagent (Sensibeads) is coated with streptavidin and contains a photosensitizer dye. Sample is incubated with biotinylated antibody and Chemibeads to form bead-CA 125-biotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the CA 125 concentration in the sample.
The LOCI 6 calibrator is a multi-analyte liquid, frozen bovine serum albumin based product containing Alpha-Fetoprotein from human cord blood, Carcinoembryonic Antigen from human cell culture and CA 125 from human cell culture. The kit consists of ten vials per level (A-E), 2.0 mL per vial. Description of the manufacturing, value assignment and stability testing process are provided in this submission report.
Here's an analysis of the provided text regarding the acceptance criteria and study for the Dimension Vista® LOCI CA 125 (CA125) Flex® Reagent Cartridge, structured according to your request:
Based on the provided 510(k) Summary of Safety and Effectiveness, this document describes an in vitro diagnostic (IVD) device meant to quantify a biomarker (CA 125) rather than a device for image analysis or other AI-based diagnostics. Therefore, many of the requested fields (like "Number of experts used to establish the ground truth for the test set," "Adjudication method," "MRMC comparative effectiveness study," and details about AI performance) are not applicable to this type of device and submission.
The "acceptance criteria" for an IVD like this are typically demonstrated through various performance characteristics, often compared to a predicate device. The "study that proves the device meets the acceptance criteria" refers to a battery of analytical performance studies (e.g., precision, accuracy/method comparison, linearity, interference, limit of detection) rather than a clinical reader study typical for imaging AI.
1. Table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in a table form with numerical targets, which is common for full submission documents but often summarized for the 510(k) summary. Instead, it states that "Comparative testing described in the submission report demonstrates substantial equivalent performance." This implies that the performance of the new device (LOCI CA 125II™ Flex® Reagent) was found to be statistically comparable to the predicate device (ADVIA Centaur CA125II assay) across various analytical parameters. The key comparison points highlighted in the document focus on feature similarities for substantial equivalence, not performance metrics.
| Feature | Acceptance Criteria (Implied: Substantial Equivalence to Predicate) | Reported Device Performance (Implied: Demonstrated Substantial Equivalence) |
|---|---|---|
| Intended Use | Similar to predicate for monitoring ovarian cancer progress/response | "Substantially equivalent" in aid of monitoring disease progress, response to therapy, or recurrent/residual disease for epithelial ovarian cancer. Not for screening or diagnosis. |
| Sample Type | Compatibility with serum (like predicate) and additional matrices | Serum, lithium heparin, and EDTA plasma (Broader than predicate's serum-only). |
| Measuring Range | Comparable to predicate (2-600 U/mL) | 1.5 - 1000 U/mL (Broader than predicate's 2-600 U/mL). |
| Sample Size | Efficacy with appropriate sample volume | 5 µL (Smaller than predicate's 50 µL). |
| Measurement Type | Chemiluminescent, sandwich immunoassay | Chemiluminescent: Homogeneous sandwich immunoassay based on LOCI® technology. |
2. Sample size used for the test set and the data provenance
The document does not detail specific sample sizes for "test sets" in the way an AI study would. For IVD devices, "test set" data usually refers to samples used in analytical performance studies (e.g., precision, linearity, method comparison).
- Sample Size: Not explicitly stated in the summary for individual analytical studies. Such details would typically be found in the full submission report's study protocols and results sections.
- Data Provenance: Not specified in the summary. For IVD analytical studies, samples often come from clinical laboratories or biobanks, and the country of origin is not always highlighted unless there's a specific regulatory or demographic reason. The studies are prospective in the sense that they are conducted specifically to validate the device's performance, but the samples themselves might be retrospective collections.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not Applicable (N/A): This is an in vitro diagnostic assay for measuring a biomarker concentration, not an imaging or AI diagnostic device requiring expert interpretation for ground truth. The "ground truth" for an IVD refers to the true concentration of the analyte, often established by reference methods or gravimetric preparation of controls/calibrators.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not Applicable (N/A): Adjudication methods are relevant for human interpretation of data, typically in clinical trials or expert consensus for image labeling. This is an automated analytical device.
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 (N/A): This is an in vitro diagnostic assay, not an AI-assisted diagnostic tool. No human readers are involved in the direct output of this device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in essence. The performance described for the LOCI CA 125II™ method is inherently "standalone" in that it's the direct analytical output of the instrument and reagents, quantifying CA 125 in a sample without human intervention in the measurement process itself. The "algorithm" here is the chemical reaction and light detection process. The summary implies the performance was evaluated on this basis.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
For an IVD assay measuring a biomarker concentration (CA 125), the "ground truth" for analytical studies would typically be:
- Reference Methods: For accuracy and method comparison, samples might be run on established, validated reference methods, or the predicate device itself serves as the comparator.
- Known Concentrations: For linearity, limit of detection, and calibration, samples are often prepared with known, certified concentrations of the analyte (e.g., using purified CA 125 antigen).
- Definitive Quantitation: In some cases, highly accurate quantitative techniques (e.g., mass spectrometry, although less common for routine biomarkers) might be considered a gold standard.
(The document does not explicitly state which ground truth method was used but it would be one of the above for an IVD.)
8. The sample size for the training set
Not Applicable (N/A): This is an in vitro diagnostic assay that is not based on machine learning or AI models requiring "training sets" in the traditional sense. The development of such assays involves reagent formulation, instrument design, and extensive analytical validation, but not machine learning training.
9. How the ground truth for the training set was established
Not Applicable (N/A): As there is no "training set" in the context of machine learning for this IVD, no ground truth was established in that manner. The "ground truth" established during the development and validation phase would be related to the chemical and physical properties of the reagents and the detection system, as described in point 7.
§ 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.