(32 days)
The ADVIA Centaur® Vitamin B12 (VB12) Master Curve Material is for in the verification of calibration and reportable range of the ADVIA Centaur VB12 assay.
The ADVIA Centaur® Total hCG (ThCG) Master Curve Material is for in the verification of calibration and reportable range of the ADVIA Centaur ThCG assay.
The ADVIA Centaur® Testosterone (TSTO) Master Curve Material is for in the verification of calibration and reportable range of the ADVIA Centaur Testosterone assay.
ADVIA Centaur® Vitamin B12 Master Curve Material is an in vitro diagnostic product containing various levels of vitamin B12 in buffered human serum albumin with sodium azide (0.2%) and preservatives. Each set contains six levels (MCM1-6); with a fill volume of 1.0 mL per level. VB12 MCMs are ready-to-use liquid products. MCM1 contains no analyte. The MCMs assigned values are lot-specific of target values: 0.00, 100, 250, 500, 1000, and 2200 pg/mL.
ADVIA Centaur® ThCG Master Curve Materials is an in vitro diagnostic product containing various levels of ThCG in lyophilized equine serum with preservatives including amphotericin B. Each set contains ten lyophilized levels (MCM1-10); with a reconstituted volume of 1.0 mL each. MCM1 contains no analyte. The ThCG MCMs assigned values are lot specific of target values: 0.0, 5.00, 10.0, 25.0, 50.0, 100, 250, 500, 750, and 1400 mIU/mL.
ADVIA Centaur® TSTO Master Curve Materials is an in vitro diagnostic product containing various levels of testosterone spiked in lyophilized human plasma with sodium azide and preservatives. Each set contains seven lyophilized levels (MCM1-7); with a reconstituted volume of 1.0 mL each. MCMI contains no analyte. The TSTO MCMs assigned values are lot specific of target values 0.00, 50.0, 100, 500, 750, 1000, and 1600 ng/dL.
Acceptance Criteria and Study for ADVIA Centaur® VB12 Master Curve Material
The document describes three separate Master Curve Materials (MCMs): VB12, ThCG, and TSTO. This analysis focuses specifically on the ADVIA Centaur® Vitamin B12 (VB12) Master Curve Material.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the ADVIA Centaur® VB12 MCMs primarily relate to their stability. The study demonstrated that the device met these criteria.
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Real Time/Shelf Life (Unopened) | - MCM1: Dose recovery ≤ 45 pg/mL |
- MCM2: % dose recovery within 75% to 125%
- MCM3-6: % dose recovery within 85% to 115%
(All calculated back to Day 0 and/or no adverse trends) | Met acceptance criteria up to the 15 months' time point, supporting a shelf-life claim of 14 months. Unopened storage shelf-life is indicated by the expiration date on the vial label. |
| On-Board Stability | - MCM1: Dose recovery ≤ 45 pg/mL - MCM2: % dose recovery within 75% to 125%
- MCM3-6: % dose recovery within 85% to 115%
(All calculated to T=0) | Met acceptance criteria up to 5 hours, supporting an on-board stability claim of 4 hours. |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Description: The test set for stability studies consisted of "Test VB12 MCMs" which were individual levels of the Master Curve Material (MCM1-6).
- Sample Size:
- Real Time/Shelf Life: Not explicitly stated as a number of individual samples, but likely involved multiple aliquots of each MCM level (MCM1-6) stored and tested at T=0, 6 months, 12 months, and 15 months. The exact number of replicates per time point is not specified but implied to be sufficient for a robust assessment.
- On-Board Stability: Not explicitly stated as a number of individual samples, but "Pooled aliquots of test VB12 MCMs in sample cups" were used and measured at T=0, 2, 4, and 5 hours. The exact number of replicates per time point is not specified.
- Data Provenance: Not explicitly stated in the provided text (e.g., country of origin). The studies appear to be prospective as they involved controlled storage and testing over defined time intervals to assess stability.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is a Quality Control (QC) material, not a diagnostic device requiring human interpretation of clinical images or data. Therefore, the concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists) does not apply. The "ground truth" for the performance of this QC material is established by analytical testing against defined reference materials and specifications.
4. Adjudication Method for the Test Set
The concept of an adjudication method (like 2+1, 3+1) is not applicable here. The performance is assessed by comparing dose recovery results to pre-defined numerical acceptance criteria for stability.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret clinical cases, often with and without AI assistance. This device is a quality control material for an in-vitro diagnostic assay.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The performance study (stability) is inherently "standalone" in the sense that it evaluates the material's integrity over time without human-in-the-loop performance, as it's a quality control product. The assay itself for which this MCM is used is automated.
7. The Type of Ground Truth Used
The ground truth for the VB12 MCM is established through:
- Traceability to a recognized standard: The assigned reference calibrators are prepared using USP (United States Pharmacopeia) VB12 stock and are traceable to USP internal material.
- Defined analytical specifications: The dose recovery acceptance criteria (e.g., ≤ 45 pg/mL, % recovery ranges) serve as the "ground truth" for determining if the material remains stable and performs as expected.
- Manufacturing procedures: MCMs are manufactured using "qualified materials and measurement procedures."
8. The Sample Size for the Training Set
This device is a physical Master Curve Material (MCM), not a machine learning model that requires a "training set" in the conventional sense. The "value assignment" process could be considered analogous to establishing its baseline characteristics.
For value assignment of a new VB12 MCM lot:
- MCM1: Run in 5 replicates on two separate runs using one reagent kit lot.
- MCM2-MCM6: Tested on 20 replicates in total, comprised of one run and four sample cups run in 5 replicates on one system and one reagent kit lot.
9. How the Ground Truth for the Training Set Was Established
As noted above, there isn't a "training set" in the machine learning context. However, the process by which the "ground truth" or assigned values for the MCMs are established is described as follows:
- Reference Calibrators: The ADVIA Centaur VB12 MCMs are value assigned using assigned reference calibrators. These calibrators are prepared using USP (United States Pharmacopeia) VB12 stock and are traceable to USP internal material.
- Value Assignment Process:
- MCM1's target is 0.0 dose, and its quality control specifications ensure it measures at or below the assay sensitivity limit.
- A nested testing run protocol is used for MCM2-MCM6, involving running alternating samples of the reference and new MCM level in the same run to remove system and run variation.
- Resulting MCM dose values are generated using a two-point calibration.
- The new MCM dose is calculated based on the relationship between the observed reference MCM dose and its assigned value.
- Performance Verification: A performance verification run with 6 replicates of each MCM level (using one instrument, one reagent kit lot, and Bio-Rad controls) is conducted. The mean MCM doses of the new lot must fall within customer range specifications.
§ 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.