(90 days)
Lumipulse G CA19-9-N is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative measurement of CA19-9 in human serum or plasma (sodium heparin, lithium heparin, or dipotassium EDTA) on the LUMIPULSE G System.
The assay is to be used as an aid in the management of patients diagnosed with cancer of the exocrine pancreas who have detectable levels of CA19-9 at some point in their disease process. Serial testing for patient CA19-9 assay values should be used in conjunction with other clinical methods used for monitoring cancer of the exocrine pancreas.
WARNING: The concentration of CA19-9 in a given specimen, as determined by assays from different manufacturers, can vary due to differences in assay methods and reagent specificity. The results reported by the laboratory to the physician must include the identity of the assay for CA 19-9 used. Values obtained with different assay methods cannot be used interchangeably. If, in the course of monitoring a patient, the assay method used for determining serial levels of CA 19-9 is changed, the laboratory must perform additional serial testing to confirm baseline values. Prior to changing assays, the laboratory MUST confirm baseline values for patients being serially monitored. Lumipulse & CA19-9-N should not be used for cancer screening or diagnosis.
WARNING: Patients known to be genotypically negative for the Lewis blood group antigen will be unable to produce the CA19-9 antigen even in the presence of malignant tissue. Phenotyping for the Lewis antigen may be insufficient to detect true Lewis antigen negative individuals. Even patients who are genotypically positive for the Lewis antigen may produce varying levels of CA19-9 based on gene dosage effect.
The Lumipulse G CA19-9-N Immunoreaction Cartridges (cat. # 235126) consists of 3 x 14 tests. Each kit contains the following:
- Antibody-Coated Particle Solution (Liquid when used, 250 µL/Immunoreaction Cartridge) Contains 150 µg/mL anti-CA19-9 monoclonal antibody (mouse)-coated particles, protein stabilizers (bovine and mouse) and chemical stabilizers in 0.15 M sodium chloride/Tris buffer. This solution contains gelatin and turns into gel at 15 °C or lower. Preservative: sodium azide.
- Enzyme-Labeled Antibody Solution (Liquid, 350 µL/Immunoreaction Cartridge) Contains 0.5 µq/mL alkaline phosphatase (ALP: calf)-labeled anti-CA19-9 monoclonal antibody (mouse), protein stabilizers (bovine, calf, and mouse) and chemical stabilizers in 0.05 M sodium chloride/Bis-Tris buffer. Preservative: sodium azide.
The provided text describes the analytical and clinical performance of the Lumipulse G CA19-9-N device, a chemiluminescent enzyme immunoassay for the quantitative measurement of CA19-9 in human serum or plasma.
Here's an analysis of the acceptance criteria and study data:
Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a codified table for each test, but rather presents the study results and implicitly demonstrates that the device's performance metrics meet internal or regulatory thresholds for clearance. Based on the provided performance characteristics, the following can be inferred as acceptance criteria and the corresponding reported performance:
| Performance Characteristic | Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| Analytical Performance | ||
| 20-Day Precision (Total %CV) | ≤ 5.3% (typical for assays around the measuring range) | ≤ 5.3% (Panel 1) |
| Site-to-site Precision (Total %CV) | ≤ 11.3% (typical for multi-site studies) | ≤ 11.3% (Panel 1) |
| Lot-to-Lot Precision (Total %CV) | ≤ 7.3% (typical for lot variability) | ≤ 7.3% (Panel 1) |
| Linearity Range | Linear correlation across the measuring range | 0.7 to 531.3 U/mL ($R^2=0.9983$) |
| Spike Recovery | 100% ± 10% of expected value | 95% to 109% |
| Measuring Range | Defined range of accurate measurement | 0.7 U/mL to 500 U/mL |
| Limit of Blank (LoB) | Very low value, close to zero | 0.10 U/mL |
| Limit of Detection (LoD) | Very low value, slightly above LoB | 0.19 U/mL |
| Functional Sensitivity (LoQ) | Low value, indicating reliable low-end measurement | 0.57 U/mL |
| Interfering Substances | Average interference ≤ 10% | Average interference ≤ 10% for all tested compounds |
| High Dose Hook Effect | No hook effect observed at very high concentrations | No hook effect observed up to 200,000 U/mL |
| Specimen Stability (Refrigerated) | Stable for up to 4 days | Stable for up to 4 days (2-10°C) |
| Specimen Stability (Frozen) | Stable for up to 14 days | Stable for up to 14 days (-20°C ±10°C) |
| Specimen Stability (On-board) | Stable for at least 3 hours | Stable for up to 3 hours |
| Manual Dilution | Recommend 1:10, 1:100, 1:200 | Recommended 1:10, 1:100, 1:200 |
| Automated Dilution | Recommend 1:10, 1:100, 1:200 for samples up to 80,000 U/mL | Recommended 1:10, 1:100, 1:200 for samples up to 80,000 U/mL |
| Matrix Comparison | Equivalency between matrices (serum, plasma types) | Demonstrated equivalency via high Pearson Correlation Coefficients (e.g., 0.9943 to 0.9981) and slopes/intercepts close to 1/0 |
| Clinical Performance | ||
| Total Concordance (Serial Monitoring) | At least 61% (for aid in management) | 61.23% |
| Sensitivity (Serial Monitoring) | At least 64% | 64.29% |
| Specificity (Serial Monitoring) | At least 60% | 60.53% |
Study Details:
This document focuses on the analytical performance and clinical utility for an in vitro diagnostic (IVD) device, specifically an immunoassay for CA19-9. It does not describe a typical image-based AI/CADe/CADx study, therefore, many of the typical questions for such studies (e.g., number of experts, adjudication method, MRMC studies, standalone performance, training set details) are not applicable (N/A) in this context.
Here's a breakdown of the information available for this IVD device:
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Sample sizes used for the test set and the data provenance:
- 20-Day Precision: 6 native human serum-based panels, tested in replicates of two separate times per day for 20 non-consecutive days (n=80 for each sample).
- Site-to-Site Precision: 6 serum samples, assayed in triplicate per run with two runs per day across five non-consecutive days for a total of ten runs per site (n=30 replicates per site). Tested at an internal lab and two additional sites.
- Lot-to-Lot Precision: 6 native serum samples, assayed in triplicate per run with 2 runs per day across 5 non-consecutive days for a total of 10 precision runs per lot (n=30 replicates per lot, 90 replicates per Panel across all three lots). Tested at the internal laboratory.
- Linearity: High and low sample pools created using patient serum samples.
- Spike Recovery: 3 normal human serum specimens.
- Detection Limit: 2 blank and 7 low-level serum specimens, tested in replicates of ten over 3 days on 2 LUMIPULSE G1200 Systems with 2 runs per day and 2 Lumipulse G CA19-9-N lots tested (60 determinations for each specimen per lot).
- Interfering Substances: Human serum specimen pools with three different CA 19-9 concentrations.
- High Dose Hook Effect: Samples containing approximately 200,000 U/mL of CA 19-9.
- Specimen Stability: Data derived from testing specimens under various storage conditions.
- Matrix Comparison: Fifty (50) matched sets of serum (red top and serum separator tubes (SST)) and plasma (K2EDTA, sodium heparin and lithium heparin) samples.
- Method Comparison: A total of 84 matched human serum samples. Later, 103 samples that required dilution were also included.
- Clinical Supportive Data (Monitoring): 83 patients, 374 pairs of observations, with an average of 5.6 observations per patient.
- Expected Values/Reference Range: 240 serum specimens from an "apparently healthy adult population" (22-93 years old).
- Disease Prevalence Studies (Contextual Data): 75 serum samples from patients with benign pancreatic conditions and 120 from patients with malignant pancreatic disease. Also, samples from patients with other benign conditions and other malignant conditions (e.g., Biliary, Breast, CRC, Gallbladder, Liver, Lung, Ovarian, Stomach cancer).
Data Provenance: Not explicitly stated regarding country of origin, but described as "native human serum-based panels," "patient serum samples," and "human serum specimens." The studies were performed at "internal laboratory," "external laboratory," and "two additional sites," suggesting clinical laboratory settings. The studies for 510(k) devices are typically retrospective, using banked clinical samples, though this is not explicitly stated as retrospective or prospective for all studies. The "Monitoring of Disease State" study with serial samples implies a prospective design in collecting follow-up data, but the collection itself might have been retrospective of existing patient records.
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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):
- N/A. This is an IVD immunoassay, not an imaging device. Ground truth for most analytical performance studies is established by the known concentration of analytes in reference materials or by comparison to a legally marketed predicate device/method.
- For the "Monitoring of Disease State" study, the "disease status" (progression/no progression) serves as the ground truth. This would typically be established by a clinician's assessment based on various clinical methods and follow-up, but the number and qualifications of such clinicians are not specified in this document.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- N/A. Not relevant for an IVD immunoassay.
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Medical Reader Multi-Case (MRMC) comparative effectiveness study:
- N/A. This is not an AI/CADe/CADx device that assists human readers.
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Standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, in essence. Diagnostic assays like this device operate standalone to produce a quantitative result. The device's performance is measured and reported directly (e.g., U/mL for CA19-9). The "human-in-the-loop" aspect is the clinician interpreting the result in conjunction with other clinical methods.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Analytical Performance: Ground truth is based on known concentrations for linearity, detection limits, spike recovery, and established reference methods (e.g., ARCHITECT CA 19-9XR as predicate) for method comparison.
- Clinical Supportive Data (Monitoring): The ground truth for correlating CA19-9 changes was "changes in disease status," defined as "disease progression" or "no progression." This "disease status" is typically determined by physician's assessment based on imaging, biopsies, clinical symptoms, and other diagnostic tests (i.e., outcomes data/clinical assessment), not pathology in itself for every observation.
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The sample size for the training set:
- N/A. This is a traditional immunoassay, not a machine learning/AI device requiring a separate "training set" in the computational sense. The "training" of such a device primarily involves the development and optimization of the reagent formulation and assay parameters based on extensive R&D data, which is distinct from a machine learning training set.
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How the ground truth for the training set was established:
- N/A. As above, not a typical AI/ML training set.
§ 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.