(49 days)
The IMMULITE® Rubella Quantitative IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Rubella Quantitative IgG assay on the IMMULITE 2000 systems.
The IMMULITE® H. pylori IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE H. pylori IgG assay on the IMMULITE 2000 systems.
The IMMULITE® Toxoplasma Quantitative IgG Calibration Verification Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Toxoplasma Quantitative IgG assay on the IMMULITE 2000 systems.
IMMULITE® 2000 Rubella Quantitative IgG Calibration Verification Material (CVM) contains one set of four vials each 1.0mL. CVM1 contains negative Rubella IgG in human serum and a buffered bovine protein matrix with preservatives. CVM2, CVM 3 and CVM4 contain various levels of Rubella IgG in human serum and buffered bovine protein matrix with preservatives.
IMMULITE® 2000 H. pylori IgG Calibration Verification Material (CVM) contains one 1 mL vial. CVM 1 contains H. pylori IgG in human serum and a buffered bovine protein matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 1 mL each. CVM1 contains negative Toxoplasma IgG in human serum in a bovine protein/buffer matrix with preservatives. CVM2, CVM3 and CVM4 contain various levels of Toxoplasma IgG in human serum in a bovine protein/buffer matrix with preservatives.
Here's an analysis of the provided text regarding the acceptance criteria and supporting studies for the IMMULITE® 2000 Calibration Verification Materials.
It's important to note that this document describes Calibration Verification Materials (CVMs), which are quality control materials used to verify the calibration of existing assays, not diagnostic devices that produce patient results. Therefore, many standard questions about diagnostic device studies (like expert ground truth, MRMC studies, standalone performance, training sets, etc.) are not applicable in this context. The focus here is on the stability and accuracy of the CVMs themselves.
Acceptance Criteria and Reported Device Performance
The document describes three distinct Calibration Verification Materials (CVMs): IMMULITE® 2000 Rubella Quantitative IgG CVM, IMMULITE® 2000 H. pylori IgG CVM, and IMMULITE® 2000 Toxoplasma Quantitative IgG CVM. Each has specific acceptance criteria for stability testing.
1. Table of Acceptance Criteria and Reported Device Performance:
| CVM Level/Analyte | Acceptance Criteria (Guideline Criteria) | Acceptable Dose Range (IU/mL or U/mL) | Reported Performance (Stability Claim) |
|---|---|---|---|
| IMMULITE® 2000 Rubella Quantitative IgG CVM | |||
| LRUBCVM1 | Not Applicable (≤5.00 IU/mL) | ≤5.00 | Stable up to 30 months at -20°C (unopened), 8 hours at 15-25°C (open) |
| LRUBCVM2 | ±15% difference to assigned dose | 7.65 - 10.4 | (Met the criteria, as implied by the FDA clearance) |
| LRUBCVM3 | ±15% difference to assigned dose | 208 – 282 | (Met the criteria, as implied by the FDA clearance) |
| LRUBCVM4 | ±20% difference to assigned dose | 404 - 606 | (Met the criteria, as implied by the FDA clearance) |
| Review Limits | Controls are within 2SD of target on each curve | N/A | (Met if guideline criteria not met, as implied by clearance) |
| IMMULITE® 2000 H. pylori IgG CVM | |||
| LHPGCVM1 | ±10% difference to assigned dose | 0.96 – 1.18 U/mL | Stable up to 24 months at -20°C (unopened), 8 hours at 15-25°C (open) |
| IMMULITE® 2000 Toxoplasma Quantitative IgG CVM | |||
| LTXPCVM1 | Not Applicable (≤5.00 IU/mL) | ≤5.00 | Stable up to 3 years at -20°C (unopened), 8 hours at 15-25°C (open) |
| LTXPCVM2 | ±10% difference to assigned dose | 9.5 - 11.7 | (Met the criteria, as implied by the FDA clearance) |
| LTXPCVM3 | ±10% difference to assigned dose | 66.2 – 80.9 | (Met the criteria, as implied by the FDA clearance) |
| LTXPCVM4 | ±24% difference to assigned dose | 281 - 459 | (Met the criteria, as implied by the FDA clearance) |
| Review Limits | Controls are within 2SD of target on each curve | N/A | (Met if guideline criteria not met, as implied by clearance) |
Note on "Reported Performance": The document states that "Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intended use" and implies that these criteria were met, leading to FDA clearance. The specific numerical performance data results demonstrating adherence to these criteria are not provided in the summary, only the criteria themselves and the resulting stability claims.
Supporting Study Information (Where Applicable)
As these are Calibration Verification Materials, the "study" referred to is primarily stability testing and value assignment validation. Many of the typical questions for diagnostic devices are not relevant here.
2. Sample size used for the test set and data provenance:
- Test Set Description: The "test set" for performance evaluation consists of the CVM lots themselves, tested over time and under various conditions (different IMMULITE 2000 systems, reagent kit lots).
- Rubella CVM: CVM lot 090 tested with L2KRUB kit lot 432.
- H. pylori CVM: CVM lot 090 tested with L2KHPG kit lot 341.
- Toxoplasma CVM: CVM lot 090 tested with L2KTXP Kit Lot 394.
- Number of Replicates: For stability time points and expected values, each CVM level was tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, and across 4 (Rubella, H. pylori) or 5 (Toxoplasma) IMMULITE 2000 systems, and 3 different reagent kit lots.
- Open Component Testing: Tested at 2-hourly intervals for up to 9 hours.
- Data Provenance: Not explicitly stated (e.g., country of origin), but implied to be from Siemens Healthcare Diagnostics' internal testing ("Non-Clinical Performance Testing"). It is a prospective study as it's validating the shelf-life and in-use stability of the product.
3. Number of experts used to establish the ground truth for the test set and qualifications of those experts:
- Not Applicable. For CVMs, the "ground truth" (assigned dose values) is established through traceability to international standards (WHO standards for Rubella and Toxoplasma, gravimetrically prepared internal standard for H. pylori) combined with internal value assignment procedures. This doesn't involve clinical expert consensus on patient diagnoses.
4. Adjudication method for the test set:
- Not Applicable. See point 3. Testing involves objective measurements against established standards and internal quality control ranges, not subjective expert review.
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. This device is a quality control material, not an AI-assisted diagnostic tool.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in essence. The performance testing described is of the CVMs themselves, and their ability to verify calibration on the IMMULITE 2000 systems. This is an "algorithm only" type of assessment in the sense that it evaluates the chemical and mechanical performance of the CVMs and the assay system, without direct human interpretation of patient results. The CVM's "performance" is its stability and accurate reflection of a known concentration within the target assay.
7. The type of ground truth used:
- Assigned Reference Calibrators traceable to international standards or gravimetric preparation.
- Rubella IgG CVM: Traceable to WHO 1st IS RUBI-1-94.
- H. pylori IgG CVM: Traceable to an internal standard which has been gravimetrically prepared.
- Toxoplasma Quantitative IgG CVM: Traceable to WHO 3rd IS for Anti-Toxoplasma Serum, Human.
- This ground truth is primarily established through analytical chemistry and metrology, not clinical outcomes or pathology.
8. The sample size for the training set:
- Not Applicable. CVMs are not machine learning models; they do not have a "training set" in the conventional sense. The "training" (development) of the assay itself would involve extensive data, but this document is about the calibration verification materials for that assay.
- For value assignment validation, the following were used:
- Rubella: Three levels of commercially available controls and 42 patient serum samples.
- H. pylori: Three levels of commercially available controls and 24 patient serum samples.
- Toxoplasma: Three levels of commercially available controls and 63 serum samples (40 patient samples and 23 normal samples).
- This "training set" (more accurately, "validation set for value assignment") is used to confirm the accuracy of the CVM's assigned values against real-world samples and other controls.
- For value assignment validation, the following were used:
9. How the ground truth for the training set was established:
- Not Applicable for a training set as these are not ML models.
- For the value assignment validation samples mentioned in point 8:
- The "ground truth" (or target values) for these commercially available controls and patient/normal serum samples would have been established through a combination of reference methods, clinical diagnosis, and highly characterized internal assays, depending on the specific sample. The document states "Quality control is performed by calculating the recovery of patient samples and controls using the assigned CVM values. The controls must fall within their target ranges." This implies these controls had pre-defined target ranges.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.