(37 days)
The IMMULITE® Cortisol Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Cortisol assay on the IMMULITE 2000 systems.
The IMMULITE® Folic Acid Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Folic Acid assay on the IMMULITE 2000 systems.
The IMMULITE® Vitanin B12 Calibration Material is for in vitro diagnostic use in the verification of calibration of the IMMULITE Vitamin B12 assay on the IMMULITE 2000 systems.
The IMMULITE® 2000 Cortisol Calibration Verification Material (CVM) contains one set of four vials each 3mL. CVM1 contains human serum with preservatives and CVM2, CVM3, and CVM4 contain various levels of cortisol in human serum with preservatives.
The IMMULITE® 2000 Folic Acid Calibration Verification Material (CVM) contains one set of four vials, 3mL (CVM1) each. when reconstituted. CVM1 contains a lyophilized human albumin based matrix with preservatives. CVM2. CVM3. and CVM4 contain various levels of lyophilized folic acid in human albumin based matrix with preservatives.
IMMULITE® 2000 Vitamin B12 Calibration Verification Material (CVM) contains one set of four vials, 3 mL each, when reconstituted. CVM1 contains a lyophilized human albumin-based matrix with preservatives. CVM2, CVM3, and CVM4 contain various levels of lyophilized Vitamin B12 in human albumin-based matrix with preservatives.
The provided text describes three distinct devices: IMMULITE® 2000 Cortisol Calibration Verification Material, IMMULITE® 2000 Folic Acid Calibration Verification Material, and IMMULITE® 2000 Vitamin B12 Calibration Verification Material. Each device has its own acceptance criteria and associated study details.
Here's an analysis for each device as requested:
Device 1: IMMULITE® 2000 Cortisol Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Dose Value Range) | Reported Device Performance (Target Mean and Guideline ±2SD Range) |
|---|---|---|
| LCOCVM1 | N/A (Guideline acceptance criteria not specified for CVM1) | Target Mean: 0.00 g/dL, Guideline Range: 0 - 1.0 g/dL |
| LCOCVM2 | ±20% of assigned dose | Target Mean: 4.54 g/dL, Guideline Range: 3.64 - 5.45 g/dL |
| LCOCVM3 | ±15% of assigned dose | Target Mean: 18.7 g/dL, Guideline Range: 15.9 - 21.5 g/dL |
| LCOCVM4 | ±19% of assigned dose | Target Mean: 54.5 g/dL, Guideline Range: 44.1 - 64.9 g/dL |
| Additional Acceptance Criteria (Part 2) | Dose value of controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. (Used if Part 1 criteria not met). | Not explicitly reported as a separate test, but implied to be met since stability study concluded product maintains optimal performance. |
| Shelf Life Stability | Stable up to 14 months when stored at -20°C prior to opening. | Confirmed by real-time shelf life study. |
| Open Component (In-use) Stability | Stable for 8 hours at ambient or room temperature (15-25°C) after opening. | Confirmed by testing at 2-hourly intervals for up to 9 hours. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Test Set):
- Stability Studies: CVM levels (LCOCVM1, LCOCVM2, LCOCVM3, LCOCVM4) run in duplicate (as a minimum) at specified time points (1, 182, 365, 425 days).
- Open Component Testing: Lot 090 CVMs were tested at 2-hourly intervals for up to 9 hours.
- Value Assignment Validation: Six levels of commercially available controls, 25 patient serum samples, 3 spiked normal serum samples, and 5 normal serum samples were used to validate calibrator/CVM value assignments.
- Expected Values/Target Values/Reference Range Establishment: Each CVM level was tested for a total of 27 replicates (9 runs, 3 replicates per run) using 3 different reagent kit lots and 8 IMMULITE 2000 systems.
- Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be based on internal laboratory studies ("Calibrators are not commercialized but are used internally during manufacture and release testing"). The studies are prospective in nature for stability testing.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Not applicable in the context of this device. Ground truth is established through internal gravimetric preparation and reference calibrator curves, with values determined by multiple runs on multiple instruments. There's no mention of human expert interpretation for device performance evaluation.
4. Adjudication Method
- Not applicable. The performance is assessed against predefined numerical acceptance criteria and statistical ranges, not through an adjudication process involving human experts.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material, not a device for human interpretation or diagnosis.
6. Standalone Performance
- Yes, the performance testing described is for the device (IMMULITE® 2000 Cortisol CVM) in a standalone context, as it evaluates the material's stability and value assignment on the IMMULITE 2000 system. It's not an AI algorithm, but the "standalone performance" concept applies in that the material's performance is assessed intrinsically.
7. Type of Ground Truth Used
- Stability and Value Assignment: Traceable to an internal material which has been gravimetrically prepared. CVMs are manufactured using qualified materials and measurement procedures. Dose values are generated from a reference calibrator curve created by assigned reference calibrators, with values averaged across all systems.
- Expected Values/Target Ranges: Established based on the Target Mean and ± 2 Standard Deviation (SD) from extensive testing (27 replicates, 9 runs, 3 replicates/run, 3 kit lots, 8 IMMULITE 2000 systems).
8. Sample Size for the Training Set
- The term "training set" is not directly applicable to a calibration verification material. However, the data used to establish the reference calibrator curve (from which CVM dose values are generated) and the target values are analogous to a training dataset in that they define the expected performance.
- For the reference calibrator curve: Not specified in detail, but it's part of the internal manufacturing and release testing of Cortisol reagents and two-point adjustors.
- For CVM Target Values: Each CVM level was tested for a total of 27 replicates (9 runs, 3 replicates per run) using 3 different reagent kit lots and 8 IMMULITE 2000 systems to establish the target mean and SD.
9. How the Ground Truth for the Training Set Was Established
- Reference Calibrator Curve: The CVMs are "value assigned using assigned reference calibrators." These calibrators are internally used during manufacture and release testing. The CVMs' dose values are generated using the curve established by these assigned reference calibrators. The underlying ground truth for these reference calibrators is based on gravimetric preparation and qualified measurement procedures.
- CVM Target Values: Established through extensive testing on multiple systems and reagent lots, calculating the mean and standard deviation from these empirical measurements, and then applying a 95% confidence interval ($\pm 2SD$).
Device 2: IMMULITE® 2000 Folic Acid Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Dose Value Range) | Reported Device Performance (Target Mean and Guideline ±2SD Range) |
|---|---|---|
| LFOCVM1 | N/A (Guideline acceptance criteria not specified for CVM1) | Target Mean: 0.00 ng/mL, Guideline Range: 0.00 - 1.0 ng/mL |
| LFOCVM2 | ±15% of assigned dose | Target Mean: 3.11 ng/mL, Guideline Range: 2.55 - 3.67 ng/mL |
| LFOCVM3 | ±10% of assigned dose | Target Mean: 12.4 ng/mL, Guideline Range: 10.9 - 13.9 ng/mL |
| LFOCVM4 | ±12% of assigned dose | Target Mean: 26.3 ng/mL, Guideline Range: 23.1 - 29.5 ng/mL |
| Additional Acceptance Criteria (Part 2) | Dose value of controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. (Used if Part 1 criteria not met). | Not explicitly reported as a separate test, but implied to be met since stability study concluded product maintains optimal performance. |
| Shelf Life Stability | Stable up to 3.5 years when stored at -20°C prior to opening. | Confirmed by real-time shelf life study. |
| Open Component (In-use) Stability | Stable for 8 hours at ambient or room temperature (15-25°C) after reconstitution. | Confirmed by testing at 2-hourly intervals for up to 9 hours. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Test Set):
- Stability Studies: CVM levels (LFOCVM1, LFOCVM2, LFOCVM3, LFOCVM4) run in duplicate (as a minimum) at specified time points (1, 912, 1095, 1280 days).
- Open Component Testing: Lot 090B Folic Acid CVMs were tested at 2-hourly intervals for up to 9 hours.
- Value Assignment Validation: Six levels of commercially available controls and 14 patient serum samples were used to validate calibrator/CVM value assignments.
- Expected Values/Target Values/Reference Range Establishment: Folic Acid CVMs were tested on 27 replicates in total (9 runs, 3 replicates per run) on 6 IMMULITE 2000 systems and 3 different reagent kit lots.
- Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be based on internal laboratory studies (calibrators used internally). The studies are prospective in nature for stability testing.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Not applicable as this is a calibration verification material. Ground truth is established through internal gravimetric preparation, reference calibrator curves, and empirical measurements on multiple instruments. No human expert interpretation is involved in performance evaluation.
4. Adjudication Method
- Not applicable. Performance is assessed against numerical acceptance criteria and statistical ranges.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material.
6. Standalone Performance
- Yes, performance testing is for the device in a standalone context, evaluating its stability and value assignment on the IMMULITE 2000 system.
7. Type of Ground Truth Used
- Stability and Value Assignment: Traceable to an internal material which has been gravimetrically prepared. CVMs are manufactured using qualified materials and measurement procedures. Dose values are generated from a reference calibrator curve created by assigned reference calibrators, with values averaged across all systems.
- Expected Values/Target Ranges: Established based on the Target Mean and ± 2 Standard Deviation (SD) from extensive testing (27 replicates, 9 runs, 3 replicates/run, 6 IMMULITE 2000 systems, 3 kit lots).
8. Sample Size for the Training Set
- Similar to the Cortisol CVM, the "training set" concept is not directly applicable.
- For the reference calibrator curve: Not specified in detail, but part of internal manufacturing and release testing of Folic Acid reagents and two-point adjustors.
- For CVM Target Values: The Folic Acid CVMs were tested on 27 replicates (9 runs, 3 replicates per run) on 6 IMMULITE 2000 systems and 3 different reagent kit lots to establish the target mean and SD.
9. How the Ground Truth for the Training Set Was Established
- Reference Calibrator Curve: The CVMs are "value assigned using assigned reference calibrators." These calibrators are internally used during manufacture and release testing. The CVMs' dose values are generated using the curve established by these assigned reference calibrators. The underlying ground truth for these reference calibrators is based on gravimetric preparation and qualified measurement procedures.
- CVM Target Values: Established through extensive empirical testing (27 replicates on multiple systems and reagent lots) to calculate the mean and standard deviation, followed by defining a 95% confidence interval ($\pm 2SD$).
Device 3: IMMULITE® 2000 Vitamin B12 Calibration Verification Material
1. Table of Acceptance Criteria and Reported Device Performance
| CVM Level | Acceptance Criteria (Part 1 - Dose Value Range) | Reported Device Performance (Target Mean and Guideline ±2SD Range) |
|---|---|---|
| LVBCVM1 | N/A (Guideline acceptance criteria not specified for CVM1) | Target Mean: 0.00 pg/mL, Guideline Range: 0.00 - 150 pg/mL |
| LVBCVM2 | ±10% of assigned dose | Target Mean: 234 pg/mL, Guideline Range: 187 - 281 pg/mL |
| LVBCVM3 | ±10% of assigned dose | Target Mean: 579 pg/mL, Guideline Range: 510 - 648 pg/mL |
| LVBCVM4 | ±21% of assigned dose | Target Mean: 1144 pg/mL, Guideline Range: 755 - 1533 pg/mL |
| Additional Acceptance Criteria (Part 2) | Dose value of controls to be within 2 Standard Deviations (SD) of the control target value when generated from the stability calibrator curve. (Used if Part 1 criteria not met). | Not explicitly reported as a separate test, but implied to be met since stability study concluded product maintains optimal performance. |
| Shelf Life Stability | Stable up to 69 months when stored at -20°C prior to opening. | Confirmed by real-time shelf life study. |
| Open Component (In-use) Stability | Stable for 8 hours at room (ambient) temperature (15-25°C) after reconstitution. | Confirmed by testing at 2-hourly intervals for up to 9 hours. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Test Set):
- Stability Studies: CVM levels (LVBCVM1, LVBCVM2, LVBCVM3, LVBCVM4) run in duplicate (at the minimum) at specified time points (0, 67, 68, 69 months).
- Open Component Testing: Lot 108 Vitamin B12 CVMs were tested at 2-hourly intervals for up to 9 hours.
- Value Assignment Validation: Eight levels of commercially available controls and 21 patient serum samples were used to validate CVM value assignments.
- Expected Values/Target Values/Reference Range Establishment: Vitamin B12 CVMs were tested on 24 replicates in total (12 runs, 2 replicates per run) using 3 IMMULITE 2000 and 5 IMMULITE/IMMULITE 1000 systems, and 4 different reagent kit lots.
- Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be based on internal laboratory studies (calibrators used internally). The studies are prospective in nature for stability testing.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Not applicable as this is a calibration verification material. Ground truth is established through internal gravimetric preparation, internal reference standards, reference calibrator curves, and empirical measurements on multiple instruments. No human expert interpretation is involved in performance evaluation.
4. Adjudication Method
- Not applicable. Performance is assessed against numerical acceptance criteria and statistical ranges.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Not applicable. This is a calibration verification material.
6. Standalone Performance
- Yes, performance testing is for the device in a standalone context, evaluating its stability and value assignment on the IMMULITE 2000 and IMMULITE/IMMULITE 1000 systems.
7. Type of Ground Truth Used
- Stability and Value Assignment: Traceable to an internal standard. CVMs are manufactured using qualified materials and measurement procedures. Dose values are generated from a reference calibrator curve created by assigned reference calibrators, with values averaged across all systems.
- Expected Values/Target Ranges: Established based on the Target Mean and ± 2 Standard Deviation (SD) from extensive testing (24 replicates, 12 runs, 2 replicates/run, 8 IMMULITE systems, 4 kit lots).
8. Sample Size for the Training Set
- The "training set" concept is not directly applicable.
- For the reference calibrator curve: Not specified in detail, but part of internal manufacturing and release testing of Vitamin B12 reagents and two-point adjustors.
- For CVM Target Values: The Vitamin B12 CVMs were tested on 24 replicates (12 runs, 2 replicates per run) using 3 IMMULITE 2000 and 5 IMMULITE/IMMULITE 1000 systems, and 4 different reagent kit lots to establish the target mean and SD.
9. How the Ground Truth for the Training Set Was Established
- Reference Calibrator Curve: The CVMs are "value assigned reference calibrators." These calibrators are internally used during manufacture and release testing. The CVMs' dose values are generated using the curve established by these assigned reference calibrators. The underlying ground truth for these reference calibrators is based on internal standards and qualified measurement procedures.
- CVM Target Values: Established through extensive empirical testing (24 replicates on multiple systems and reagent lots) to calculate the mean and standard deviation, followed by defining a 95% confidence interval ($\pm 2SD$).
§ 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.