(133 days)
The IMMULITE® 2000 AFP Calibration Material (CVM) is intended for monitoring system performance of the IMMULITE Immunoassay system for the quantitative measurement of AFP antigen.
The IMMULITE® BR-MA Calibration Verification Material (CVM) is for in the verification of calibration and reportable range of the IMMULITE BR-MA assay on the IMMULITE 2000 systems
The IMMULITE® OM-MA Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration and reportable range of the IMMULITE OM-MA assay on the IMMULITE 2000 systems
The Calibration Verification Material (CVM) contains one set of four vials each 3mL. CVM1 contain bovine serum matrix with preservatives. CVM2, CVM 3 and CVM4 contain low, intermediate and high levels of human source AFP respectively, in a bovine serum matrix with preservatives. CVMs are supplied frozen in a liquid form.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. CVM 1 contains a bovine serum matrix with preservatives. CVM2. CVM3 and CVM4 contain low, intermediate and high levels of human source CA 15-3 in a bovine serum matrix with preservatives. CVMs are supplied frozen in liquid form. In addition to using the CVM at their manufactured concentrations, alternate concentrations may be obtained by accurately diluting the assay-specific calibrator levels with each other.
The Calibration Verification Material (CVM) contains one set of four vials. 2 mL each. CVM 1 contains a bovine protein/buffer matrix with preservatives. CVM2. CVM3 and CVM4, contain low, intermediate and high levels of CA 125 in a bovine protein/buffer matrix with preservatives. CVMs are supplied in Iyophilized form.
This document describes the validation of three Calibration Verification Materials (CVMs): IMMULITE® 2000 OM-MA CVM, IMMULITE® 2000 BR-MA CVM, and IMMULITE® 2000 AFP CVM. Each CVM's acceptance criteria and performance study are outlined below.
IMMULITE® 2000 OM-MA Calibration Verification Material (CVM)
1. Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Guideline) | Follow-up Criteria (Part 2 - Review Limits) | Reported Performance (Dose Value) |
|---|---|---|---|
| CVM1 (LOPCVM1) | (Implicitly, stable at 0.00 U/mL) | Within 2SD of control target value | Not explicitly stated for performance, but target mean is 0.00 U/mL |
| CVM2 (LOPCVM2) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 7.70 U/mL |
| CVM3 (LOPCVM3) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 57.0 U/mL |
| CVM4 (LOPCVM4) | Within ±11% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 609 U/mL |
| (85% CVM4 + 15% CVM1) | (Within ±10% of reportable range for CVM4 dilution) | (Within ±10% of reportable range for CVM4 dilution) | Not explicitly stated, but target mean is 518 U/mL |
2. Sample Size and Data Provenance
- Test Set Sample Size: 27 replicates for each CVM level, comprised of 9 runs and 3 replicates per run.
- Data Provenance: The study was conducted internally by Siemens Healthcare Diagnostics Inc. No country of origin for the data is specified beyond that. The study appears to be prospective in nature for stability testing.
3. Number of Experts and Qualifications for Ground Truth
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay. Ground truth is established through internal assigned reference calibrators and gravimetrically prepared internal material, not expert consensus.
4. Adjudication Method for Test Set
- Not applicable. Performance is based on quantitative measurements against predefined criteria.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material, not an AI-assisted diagnostic tool for human readers.
6. Standalone Performance
- Yes, a standalone performance study was conducted in the form of stability testing and value assignment. The CVMs were tested independently on IMMULITE 2000 systems.
7. Type of Ground Truth Used
- Internal assigned reference calibrators prepared using OM-MA antigen stock solution.
- Internal material that is gravimetrically prepared.
- Value assignment was validated using commercially available controls and patient samples (5 normal, 25 normal spiked with high patient sample).
8. Sample Size for Training Set
- Not applicable in the typical sense of a 'training set' for a machine learning algorithm. The "value assignment" process involves generating curves from assigned reference calibrators and testing on multiple replicates. This is more akin to a robust characterization and validation process rather than machine learning training.
9. How Ground Truth for Training Set was Established
- Not applicable. The "ground truth" for the calibrators is established through their preparation (OM-MA antigen stock solution, gravimetric preparation) and characterization against reference materials.
IMMULITE® 2000 BR-MA Calibration Verification Material (CVM)
1. Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Guideline) | Follow-up Criteria (Part 2 - Review Limits) | Reported Performance (Dose Value) |
|---|---|---|---|
| CVM1 (LBRCVM1) | (Implicitly, stable at 0.00 U/mL) | Within 2SD of control target value | Not explicitly stated for performance, but target mean is 0.00 U/mL |
| CVM2 (LBRCVM2) | Within ±15% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 18.8 U/mL |
| CVM3 (LBRCVM3) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 165 U/mL |
| CVM4 (LBRCVM4) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 291 U/mL |
2. Sample Size and Data Provenance
- Test Set Sample Size: 27 replicates for each CVM level, comprised of 9 runs and 3 replicates per run.
- Data Provenance: The study was conducted internally by Siemens Healthcare Diagnostics Inc. No country of origin for the data is specified beyond that. The study appears to be prospective in nature for stability testing.
3. Number of Experts and Qualifications for Ground Truth
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay. Ground truth is established through internal assigned reference calibrators and gravimetrically prepared internal material, not expert consensus.
4. Adjudication Method for Test Set
- Not applicable. Performance is based on quantitative measurements against predefined criteria.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material, not an AI-assisted diagnostic tool for human readers.
6. Standalone Performance
- Yes, a standalone performance study was conducted in the form of stability testing and value assignment. The CVMs were tested independently on IMMULITE 2000 systems.
7. Type of Ground Truth Used
- Internal assigned reference calibrators prepared using BR-MA antigen stock solution.
- Internal material that is gravimetrically prepared.
- Value assignment was validated using commercially available controls and patient samples (5 normal, 25 spiked patient samples).
8. Sample Size for Training Set
- Not applicable in the typical sense of a 'training set' for a machine learning algorithm. The "value assignment" process involves generating curves from assigned reference calibrators and testing on multiple replicates. This is more akin to a robust characterization and validation process rather than machine learning training.
9. How Ground Truth for Training Set was Established
- Not applicable. The "ground truth" for the calibrators is established through their preparation (BR-MA antigen stock solution, gravimetric preparation) and characterization against reference materials.
IMMULITE® 2000 AFP Calibration Verification Material (CVM)
1. Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Guideline) | Follow-up Criteria (Part 2 - Review Limits) | Reported Performance (Dose Value) |
|---|---|---|---|
| CVM1 (LAPCVM1) | (Implicitly, stable at 0.00 IU/mL) | Within 2SD of control target value | Not explicitly stated for performance, but target mean is 0.00 IU/mL |
| CVM2 (LAPCVM2) | Within ±15% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 3.03 IU/mL |
| CVM3 (LAPCVM3) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 47.9 IU/mL |
| CVM4 (LAPCVM4) | Within ±10% of assigned dose | Within 2SD of control target value | Not explicitly stated, but target mean is 413 IU/mL |
| (75% CVM4 + 25% CVM1) | (Within ±10% of reportable range for CVM4 dilution) | (Within ±10% of reportable range for CVM4 dilution) | Not explicitly stated, but target mean is 310 IU/mL |
2. Sample Size and Data Provenance
- Test Set Sample Size: 27 replicates for each CVM level, comprised of 9 runs and 3 replicates per run.
- Data Provenance: The study was conducted internally by Siemens Healthcare Diagnostics Inc. No country of origin for the data is specified beyond that. The study appears to be prospective in nature for stability testing.
3. Number of Experts and Qualifications for Ground Truth
- Not applicable. This device is a calibration verification material for an in vitro diagnostic assay. Ground truth is established through traceability to WHO 1st IS 72/225 and qualified internal materials, not expert consensus.
4. Adjudication Method for Test Set
- Not applicable. Performance is based on quantitative measurements against predefined criteria.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material, not an AI-assisted diagnostic tool for human readers.
6. Standalone Performance
- Yes, a standalone performance study was conducted in the form of stability testing and value assignment. The CVMs were tested independently on IMMULITE 2000 systems.
7. Type of Ground Truth Used
- Traceable to WHO 1st IS 72/225.
- Manufactured using qualified materials and measurement procedures.
- Value assignment was validated using commercially available controls and 61 samples (amniotic fluid samples, pregnancy trimester samples, normal patient samples, and spiked AFP samples).
8. Sample Size for Training Set
- Not applicable in the typical sense of a 'training set' for a machine learning algorithm. The "value assignment" process involves generating curves from assigned reference calibrators and testing on multiple replicates. This is more akin to a robust characterization and validation process rather than machine learning training.
9. How Ground Truth for Training Set was Established
- Not applicable. The "ground truth" for the calibrators is established through traceability to WHO 1st IS 72/225 and their preparation using qualified materials and measurement procedures.
§ 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.