(30 days)
The IMMULITE 2000 DHEA-SO4 Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE DHEA-SO4 assay on the IMMULITE 2000 systems.
The IMMULITE 2000 Third Generation Verification Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Third Generation TSH assay on the IMMULITE 2000 systems.
The IMMULITE 2000 Intact PTH Calibration Material (CVM) is intended for in vitro diagnostic use in the verification of calibration of the IMMULITE Intact PTH assay on the IMMULITE 2000 systems.
The Calibration Verification Material (CVM) contains one set of four vials each 2.0mL after reconstitution. CVM1 contains human serum with preservatives. CVM2, CVM 3 and CVM4 contain various levels of lyophilized DHEA-SO4 in human serum with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, 3 mL each after reconstitution. CVM 1 contains an equine serum/buffer matrix with preservatives. CVM2. CVM3 and CVM4 various levels of lyophilized TSH in an equine serum/buffer matrix with preservatives.
The Calibration Verification Material (CVM) contains one set of four vials, with 4 mL for CVM1 and 2 mL each for CVM2, CVM3 and CVM4 after reconstitution. CVM1 contains a buffered bovine protein matrix with preservatives. CVM2, CVM3 and CVM4 contain various levels of lyophilized synthetic human intact PTH in buffered bovine protein matrix with preservatives.
Here's a breakdown of the acceptance criteria and study information for each of the three devices mentioned in the document: IMMULITE® 2000 DHEA-SO4 Calibration Verification Material, IMMULITE® 2000 Third Generation TSH Calibration Verification Material, and IMMULITE® 2000 Intact PTH Calibration Verification Material.
Device 1: IMMULITE® 2000 DHEA-SO4 Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline) | Acceptable Dose Range (µg/dL) | Reported Performance (Implied by meeting criteria) |
|---|---|---|---|
| LDSCVM1 | Not Applicable (Controls within 2SD of target) | Not Applicable | Met (controls within 2SD) |
| LDSCVM2 | Dose value between ±15% of assigned dose | 39.9 - 53.9 | Met (within 39.9 - 53.9 µg/dL) |
| LDSCVM3 | Dose value between ±10% of assigned dose | 437.4 - 534.6 | Met (within 437.4 - 534.6 µg/dL) |
| LDSCVM4 | Dose value between ±15% of assigned dose | 894.2 - 1209.8 | Met (within 894.2 - 1209.8 µg/dL) |
Note: The document states that the device "meets the performance specifications for its intended use" and "supports the claims of substantial equivalence," implying that these stability acceptance criteria were met.
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: Each CVM level was tested on 27 replicates in total, comprised of 9 runs, 3 replicates per run, on 9 systems and 4 different reagent kit lots.
- Data Provenance: Not explicitly stated, but assumed to be internal laboratory data generated by Siemens Healthcare Diagnostics Inc. This is a prospective study for stability testing.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable. The ground truth (assigned dose values) for the CVMs are established through internal reference calibrators prepared gravimetrically and validated using quality control and patient samples. No human expert 'ground truth' is explicitly mentioned for the test set evaluation.
4. Adjudication method for the test set
- Two-part criteria:
- Part 1 (Guideline Criteria): Dose value of stability calibrators/CVM must fall within specified percentage differences of the assigned dose (e.g., ±15% for CVM level 2).
- Part 2 (Review Limits Criteria): If Part 1 is not met, a secondary review is conducted, requiring the dose value of controls to be within 2 standard deviations (SD) of the control target value when generated from the stability calibrator curve.
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 is a performance study for an in vitro diagnostic calibration verification material, not an AI-assisted diagnostic device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material.
7. The type of ground truth used
- Assigned Dose Values: Ground truth for the CVMs (assigned dose values) is established through internal reference calibrators prepared gravimetrically. This is a form of traceable reference standard. Validation also includes testing with commercially available controls and normal human serum samples.
8. The sample size for the training set
- Not applicable in the context of a "training set" for an algorithm. However, for "value assignment" (which establishes the initial reference values these CVMs verify), six levels of commercially available controls and 30 normal serum samples were used.
9. How the ground truth for the training set was established
- Not applicable as a "training set". For value assignment (establishment of reference values), the IMMULITE DHEA-SO4 CVMs are traceable to an internal material that has been gravimetrically prepared. The CVMs are a subset of 7-level DHEA-SO4 calibrators. These calibrators are value assigned using assigned reference calibrators prepared using DHEA-SO4 antigen stock traceable to gravimetrically prepared internal material.
Device 2: IMMULITE® 2000 Third Generation TSH Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline) | Acceptable Dose Range (µIU/mL) | Reported Performance (Implied by meeting criteria) |
|---|---|---|---|
| LTSCVM1 | Not Applicable (Controls within 2SD of target) | Not Applicable | Met (controls within 2SD) |
| LTSCVM2 | Dose value between ±10% of assigned dose | 0.52 - 0.64 | Met (within 0.52 - 0.64 µIU/mL) |
| LTSCVM3 | Dose value between ±12% of assigned dose | 3.81 - 4.85 | Met (within 3.81 - 4.85 µIU/mL) |
| LTSCVM4 | Dose value between ±16% of assigned dose | 63.00 - 87.00 | Met (within 63.00 - 87.00 µIU/mL) |
Note: The document states that the device "meets the performance specifications for its intended use" and "supports the claims of substantial equivalence," implying that these stability acceptance criteria were met.
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: Each CVM level was tested on 15 replicates in total, comprised of 5 runs, 3 replicates per run, on 5 systems and 5 different reagent kit lots.
- Data Provenance: Not explicitly stated, but assumed to be internal laboratory data generated by Siemens Healthcare Diagnostics Inc. This is a prospective study for stability testing.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable. The ground truth (assigned dose values) for the CVMs are established through internal reference calibrators prepared using human TSH antigen spiked in an equine serum matrix and validated using quality control and patient samples. No human expert 'ground truth' is explicitly mentioned for the test set evaluation.
4. Adjudication method for the test set
- Two-part criteria:
- Part 1 (Guideline Criteria): Dose value of stability calibrators/CVM must fall within specified percentage differences of the assigned dose (e.g., ±10% for CVM level 2).
- Part 2 (Review Limits Criteria): If Part 1 is not met, a secondary review is conducted, requiring the dose value of controls to be within 2 standard deviations (SD) of the control target value when generated from the stability calibrator curve.
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 is a performance study for an in vitro diagnostic calibration verification material, not an AI-assisted diagnostic device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material.
7. The type of ground truth used
- Assigned Dose Values (Traceable Reference Standard): Ground truth for the CVMs is traceable to WHO 2nd IRP 80/558. Additionally, the assigned reference calibrators are prepared using human TSH antigen spiked in equine serum matrix. Validation also includes testing with commercially available controls and spiked/normal patient samples.
8. The sample size for the training set
- Not applicable in the context of a "training set" for an algorithm. However, for "value assignment," seven levels of commercially available controls and 30 samples (10 spiked patient, 15 spiked normal, and 5 normal samples) were used to validate calibrator/CVM value assignments.
9. How the ground truth for the training set was established
- Not applicable as a "training set". For value assignment (establishment of reference values), the IMMULITE Third Generation TSH CVMs are traceable to WHO 2nd IRP 80/558. Calibrators (of which CVMs are a subset) are value assigned using assigned reference calibrators prepared using human TSH antigen spiked in an Equine Serum matrix with preservatives.
Device 3: IMMULITE® 2000 Intact PTH Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Guideline) | Acceptable Dose Range (pg/mL) | Reported Performance (Implied by meeting criteria) |
|---|---|---|---|
| LPPCVM1 | Not Applicable (Controls within 2SD of target) | Not Applicable | Met (controls within 2SD) |
| LPPCVM2 | Dose value between ±12% of assigned dose | 13.4 - 17.0 | Met (within 13.4 - 17.0 pg/mL) |
| LPPCVM3 | Dose value between ±8% of assigned dose | 141.7 - 166.3 | Met (within 141.7 - 166.3 pg/mL) |
| LPPCVM4 | Dose value between ±12% of assigned dose | 3329.9 - 4238.1 | Met (within 3329.9 - 4238.1 pg/mL) |
Note: The document states that the device "meets the performance specifications for its intended use" and "supports the claims of substantial equivalence," implying that these stability acceptance criteria were met.
2. Sample size used for the test set and the data provenance
- Test Set Sample Size: Each CVM level was tested on 27 replicates in total, comprised of 9 runs, 7 systems and 3 different reagent kit lots.
- Data Provenance: Not explicitly stated, but assumed to be internal laboratory data generated by Siemens Healthcare Diagnostics Inc. This is a prospective study for stability testing.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable. The ground truth (assigned dose values) for the CVMs are established through internal reference calibrators prepared using synthetic human intact PTH and validated using quality control and patient samples. No human expert 'ground truth' is explicitly mentioned for the test set evaluation.
4. Adjudication method for the test set
- Two-part criteria:
- Part 1 (Guideline Criteria): Dose value of stability calibrator/CVM must fall within specified percentage differences of the assigned dose (e.g., ±12% for CVM level 2).
- Part 2 (Review Limits Criteria): If Part 1 is not met, a secondary review is conducted, requiring the dose value of controls to be within 2 standard deviations (SD) of the control target value when generated from the stability calibrator curve.
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 is a performance study for an in vitro diagnostic calibration verification material, not an AI-assisted diagnostic device.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not applicable. This is a performance study for an in vitro diagnostic calibration verification material.
7. The type of ground truth used
- Assigned Dose Values (Traceable Reference Standard): Ground truth for the CVMs is traceable to an internal material that has been gravimetrically prepared. Assigned reference calibrators are prepared using synthetic Human Intact PTH (1-84) spiked in buffered bovine protein matrix. Validation also includes testing with commercially available controls and various patient samples (EDTA plasma, serum, EDTA dialysis, serum dialysis).
8. The sample size for the training set
- Not applicable in the context of a "training set" for an algorithm. However, for "value assignment," two levels of commercially available controls and 88 samples (32 EDTA plasma, 32 serum, 12 EDTA dialysis samples, and 12 serum dialysis samples) were used to validate calibrator/CVM value assignments.
9. How the ground truth for the training set was established
- Not applicable as a "training set". For value assignment (establishment of reference values), the IMMULITE Intact PTH CVMs are traceable to an internal material that has been gravimetrically prepared. Calibrators (of which CVMs are a subset) are value assigned using assigned reference calibrators prepared using synthetic Human Intact PTH (1-84) spiked in the buffered bovine protein matrix.
§ 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.