(50 days)
The IMMULITE® Anti-TG Ab Calibration Material (CVM) is for in vitro diagnostic use in the verification of callbration of the IMMULITE Anti-TG Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.
The IMMULITE® Thyroglobulin Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Thyroglobulin assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.
The IMMULITE® Anti-TPO Ab Calibration Material (CVM) is for in vitro diagnostic use in the verification of calibration of the IMMULITE Anti-TPO Ab assay on the IMMULITE 2000 systems as indicated in the CVM Package Insert.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTGCVM i contains human serum/ buffer matrix with preservatives. LTGCVM2, LTGCVM3 and LTGCVM4 contain low, intermediate and high levels of Anti-TG Ab respectively, in human serum/ buffer matrix matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTOCVM1 contains human serum/ buffer matrix with preservatives. LTOCVM2, LTOCVM3 and LTOCVM4 contain low, intermediate and high levels of Anti-TPO Ab respectively, in human serum/ buffer matrix matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 2 mL each. LTYCVM1 in horse serum matrix with preservatives. LTYCVM2. LTYCVM3 and LTYCVM4 contain low, intermediate and high levels of Thyroglobulin respectively, in horse serum matrix with preservatives.
This document describes the acceptance criteria and supporting studies for three calibration verification materials (CVMs): IMMULITE® 2000 Anti-TG Ab, IMMULITE® 2000 Anti-TPO Ab, and IMMULITE® 2000 Thyroglobulin.
1. Table of Acceptance Criteria and Reported Device Performance
This information is derived from the "Stability Acceptance Criteria Summary" and "Expected Values/Reference Range" sections for each device.
IMMULITE® 2000 Anti-TG Ab Calibration Verification Material
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance | Comments |
|---|---|---|---|
| Stability (Part 1: Guideline) | Dose value stability CVM to fall between ±15% of the assigned dose. | Stable up to 7 years when stored refrigerated at 2-8°C prior to opening. | Study indicates device meets this criterion based on the given shelf-life. |
| Stability (Part 2: Review Limits) | Dose value of controls to be within 2SD of the control target value generated from the stability calibrator curve. (Used if Part 1 fails). | Not explicitly stated as a pass/fail condition in table format, but described as a review process. The stability study supports the 7-year shelf life under these criteria. | This is a secondary acceptance criterion for review, not a primary pass/fail for the table. |
| Expected Values/Reference Range | Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and ± 2 Standard Deviation (SD). | Level 1: 0.00 ≤ 20.00 IU/mL | |
| Level 2 (50% CVM1): 36.8 IU/mL (SD not specified for this level) | |||
| Level 2 (50% CVM2): No performance data provided. | |||
| Level 3: 384 - 520 IU/mL (Target Mean 452, SD 34) | |||
| Level 4: 2661 - 3600 IU/mL (Target Mean 3130, SD 234.75) | These ranges are considered guidelines, with laboratories needing to establish their own limits. Device performance is described as generating these target values and SDs. | ||
| Assay Range | 20-3000 IU/mL | 20-3000 IU/mL | The CVMs cover this range. |
IMMULITE® 2000 Anti-TPO Ab Calibration Verification Material
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance | Comments |
|---|---|---|---|
| Stability (Part 1: Guideline) | Dose value stability CVM to fall between: | ||
| ±25% of assigned dose for CVM level 2 | |||
| ±15% of assigned dose for CVM levels 3 and 4 | Stable up to 9 years when stored refrigerated at 2-8°C prior to opening. | Study indicates device meets this criterion based on the given shelf-life. | |
| Stability (Part 2: Review Limits) | Dose value of controls to be within 2SD of the control target value generated from the stability calibrator curve. (Used if Part 1 fails). | Not explicitly stated as a pass/fail condition in table format, but described as a review process. The stability study supports the 9-year shelf life under these criteria. | This is a secondary acceptance criterion for review, not a primary pass/fail for the table. |
| Expected Values/Reference Range | Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and ± 2 Standard Deviation (SD). | Level 1: ≤ 10.00 IU/mL | |
| Level 2: 27.3 - 40.9 IU/mL (Target Mean 34.1, SD 3.4) | |||
| Level 3: 239 - 323 IU/mL (Target Mean 281, SD 21) | |||
| Level 4: 808 - 1093 IU/mL (Target Mean 950, SD 71.25) | These ranges are considered guidelines, with laboratories needing to establish their own limits. Device performance is described as generating these target values and SDs. | ||
| Assay Range | 10-1000 IU/mL | 10-1000 IU/mL | The CVMs cover this range. |
IMMULITE® 2000 Thyroglobulin Calibration Verification Material
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance | Comments |
|---|---|---|---|
| Stability (Part 1: Guideline) | Dose value stability CVM to fall between ±10% of the assigned dose. | Stable up to 6 years when stored refrigerated at 2-8°C prior to opening. | Study indicates device meets this criterion based on the given shelf-life. |
| Stability (Part 2: Review Limits) | Dose value of controls to be within 2SD of the control target value generated from the stability calibrator curve. (Used if Part 1 fails). | Not explicitly stated as a pass/fail condition in table format, but described as a review process. The stability study supports the 6-year shelf life under these criteria. | This is a secondary acceptance criterion for review, not a primary pass/fail for the table. |
| Expected Values/Reference Range | Guideline Range (95% confidence interval) for each CVM level established based on Target Mean and ± 2 Standard Deviation (SD). | Level 1: 0.00 ≤ 20.0 ng/mL | |
| Level 2: 8.10 - 10.1 ng/mL (Target Mean 9.10, SD 0.5) | |||
| Level 3: 31.9 - 40.5 ng/mL (Target Mean 36.2, SD 2.15) | |||
| Level 4: No Guideline Range provided (Target Mean 430, SD not specified) | |||
| 70% CVM4: 259 - 343 ng/mL (Target Mean 301, SD 21) | These ranges are considered guidelines, with laboratories needing to establish their own limits. Device performance is described as generating these target values and SDs. | ||
| Assay Range | 0.2-300 NG/mL | 0.2-300 ng/mL | The CVMs cover this range. |
Study Information for All Devices (IMMULITE® 2000 Anti-TG Ab, Anti-TPO Ab, and Thyroglobulin CVMs)
The studies described are primarily stability and value assignment studies to establish the shelf-life and assigned values of the Calibration Verification Materials.
2. Sample Size Used for the Test Set and Data Provenance
The "test set" for performance evaluation consists of the replicates used to determine the CVMs' target values and assess their stability.
- Sample Size: For each CVM (Anti-TG Ab, Anti-TPO Ab, Thyroglobulin), the CVMs were tested on 27 replicates in total, comprised of nine runs and three replicates per run.
- Data Provenance: The data appears to be prospective as it involves controlled testing in a laboratory setting to assign values and assess stability over time. The origin of the patient samples used for validation is not specified (e.g., country of origin).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The concept of "experts" in the traditional sense (e.g., radiologists) is not applicable here as these are in-vitro diagnostic calibration materials. The "ground truth" or reference values are established through rigorous laboratory procedures and traceability to international standards.
- Number of Experts: Not applicable in the context of expert consensus for diagnostic interpretation.
- Qualifications of Experts: The ground truth is established through qualified technical staff and validated measurement procedures traceable to WHO International Reference Preparations or Certified Reference Materials (e.g., WHO 1st IRP 65/93 for Anti-TG Ab, WHO 15 IRP 66/387 for Anti-TPO Ab, and BCR 457 for Thyroglobulin).
4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set
Adjudication methods like 2+1 or 3+1 are typically used for subjective diagnostic interpretations by multiple readers. This is not applicable to the quantitative measurements performed for these CVMs.
- Adjudication Method: Not applicable. The process involves calculating average values across multiple runs and instruments.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
MRMC studies involving human readers are designed for diagnostic interpretation tasks, which is not the function of these CVMs.
- MRMC Study: No, a Multi-Reader Multi-Case comparative effectiveness study was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
These devices are calibration verification materials for automated immunoassay systems. Their "standalone performance" is exactly what is tested: their ability to provide stable and accurate reference values when processed by the IMMULITE 2000 systems. The performance data presented (target means, SDs, and stability) represents the standalone performance of the CVMs in conjunction with the IMMULITE 2000 systems.
- Standalone Performance: Yes, the described stability and value assignment studies represent the standalone performance of the CVMs when used with the IMMULITE 2000 systems.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for these CVMs is based on traceability to international reference standards and rigorous value assignment procedures.
- Type of Ground Truth:
- Traceability to International Standards:
- IMMULITE® 2000 Anti-TG Ab CVMs are traceable to WHO 1st IRP 65/93.
- IMMULITE® 2000 Anti-TPO Ab CVMs are traceable to WHO 15 IRP 66/387.
- IMMULITE® 2000 Thyroglobulin CVMs are traceable to Certified Reference Material from human thyroglobulin (BCR 457).
- Value Assignment Procedure: The CVMs are manufactured using qualified materials and measurement procedures. Their dose values are generated using curves from assigned reference calibrators, which are themselves traceable to the international standards.
- Traceability to International Standards:
8. The Sample Size for the Training Set
The concept of a "training set" typically applies to machine learning algorithms. For these CVMs, the "training" equivalent would be the extensive manufacturing and internal calibration processes that establish the reference calibrators and assigned values.
- Sample Size for Training Set: Not explicitly defined in terms of a "training set" like in AI/ML. However, the internal manufacturing and value assignment processes involve various calibrator lots and materials that indirectly serve this purpose. The document mentions "8 level Anti-TG Ab calibrators," "7 level Anti-TPO Ab calibrators," and "9 level Thyroglobulin calibrators" used internally during manufacture and release testing. These calibrators would form the basis for the "training" of the system's ability to measure the analytes.
9. How the Ground Truth for the Training Set Was Established
Similar to point 8, the "ground truth for the training set" refers to the establishment of the reference for the internal calibrators that are used to assign values to these CVMs.
- Ground Truth for Training Set: The ground truth for the internal reference calibrators is established through:
- Traceability to WHO International Reference Preparations or Certified Reference Materials: As detailed in point 7.
- Use of Qualified Materials and Measurement Procedures: The calibrators are prepared using specific antibody stocks (e.g., Anti-TG antibody stock, Anti-TPO antibody stock) and are carefully manufactured.
- Validation with Patient Samples and Controls: For value assignment validation, the documents state:
- Anti-TG Ab: "Two levels of commercially available controls, and 30 patient samples (10 spiked normal patients samples, two patient samples and 18 spiked samples) are used to validate CVM value assignments."
- Anti-TPO Ab: "Two levels of commercially available controls, and 30 patient samples and 25 spiked samples) are used to validate CVM value assignments."
- Thyroglobulin: "Three levels of commercially available controls, and 30 patient samples (5 normal patients samples and 25 spiked samples) are used to validate CVM value assignments."
This indicates a thorough process of establishing reliable reference values for the materials.
§ 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.