(28 days)
Lumipulse G Progesterone-N Calibrators are for in vitro diagnostic use in the calibration of Lumipulse G Progesterone-N on the LUMIPULSE G System.
Lumipulse G Progesterone-N Calibrator kit contains 3 bottles (1.5 mL each) of Lumipulse G Progesterone-N Calibrators 1, 2, and 3. Calibrators 1, 2, and 3 contain progesterone in 0.15 M sodium chloride in MES buffer with protein (bovine) and chemical stabilizers. Preservative: sodium azide.
Lumipulse G Progesterone-N Calibrators CAL 230893, Liquid 1x3 concentrations Each calibrator kit contains one bottle each of Calibrators 1 – 3. The calibrator kit is packaged separately.
CAL 1 0 ng/mL Progesterone calibrator (1 × 1.5 mL) CAL 2 0.5 ng/mL Progesterone calibrator (1 x 1.5 mL) 40 ng/mL Progesterone calibrator (1 x 1.5 mL) CAL 3 *Contains progesterone in 0.15 M sodium chloride in MES buffer with protein (bovine) and chemical stabilizers. Preservative: sodium azide.
This document is a 510(k) Premarket Notification for the Lumipulse® G Progesterone-N Calibrators. It focuses heavily on the stability and traceability of the calibrators rather than the performance of a diagnostic device in terms of clinical sensitivity or specificity. Therefore, many standard AI device performance metrics (like those relying on true positives, negatives, and human reader studies) are not applicable.
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1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria and performance data are primarily related to the stability and manufacturing consistency of the calibrators.
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance | Study Name/Location |
|---|---|---|---|
| Long-Term Stability (9 months, 2-10°C) | Fujirebio, Inc. (Tokyo, Japan) | ||
| Sensitivity (Luminescence Ratio) | Ratio ≥ 1.2 (Cal 1 / Cal 2) | 1.6 (met criteria) | Long-term stability study (9 months) |
| Accuracy (Serum samples) | 100 ± 20% for each replicate | 100 ± 20% (met criteria) | Long-term stability study (9 months) |
| Reproducibility (Serum samples) | CV ≤ 15% for each sample | ≤ 15% (met criteria) | Long-term stability study (9 months) |
| Real-Time (Intended Storage) Stability (4 months, 2-10°C) | Fujirebio Diagnostics, Inc. (Malvern, PA) | ||
| Percent difference (Calibrator panels) | Values stable, acceptance criteria met | Met criteria for 4 months (study ongoing for 9 months) | Real-time stability study (4 months) |
| Open-Vial (In-Use) Stability (4 months, 2-10°C) | Fujirebio Diagnostics, Inc. (Malvern, PA) | ||
| Percent difference (Calibrator panels) | Values stable, acceptance criteria met | Met criteria for 4 months (study ongoing for 9 months) | Open-vial stability study (4 months) |
| Transport Simulation (Temperature stress) | Fujirebio, Inc. (Tokyo, Japan) | ||
| Sensitivity (Luminescence Ratio) | Ratio ≥ 1.2 (Cal 1 / Cal 2) | 1.6 (met criteria) | Transport Simulation (Temperature) |
| Accuracy (Panel concentration) | 100 ± 20% | 86-120% (met criteria) | Transport Simulation (Temperature) |
| Transport Simulation (Temperature stress, Malvern) | Fujirebio Diagnostics, Inc. (Malvern, PA) | ||
| %CV (Initial) | ≤ 10% | Met criteria | Transport Simulation (Temperature) |
| Appearance (IC) | Met visual inspection criteria | Met criteria | Transport Simulation (Temperature) |
| Mean concentration (4 months) | Within ± 10% of Time 0 | Met criteria | Transport Simulation (Temperature) |
| %CV (4 months) | ≤ 10% | Met criteria | Transport Simulation (Temperature) |
| Appearance (IC, 4 months) | Met visual inspection criteria | Met criteria | Transport Simulation (Temperature) |
| Traceability | Traceable to ERM-DA347 and BCR-348R by IRMM | Confirmed by gravimetric preparation and direct traceability statement. | Value Assignment & Traceability Studies |
| Value Assignment (Mean Ratio) | 0.95 - 1.05 | Not explicitly stated but implied as "acceptable rate mean ratio" leading to assigned value. | Value Assignment Process |
2. Sample Sizes Used for the Test Set and Data Provenance
The "test set" in this context refers to the samples and calibrator lots used in the stability and value assignment studies.
- Long-Term Stability & Open-Vial/Real-Time Stability:
- Calibrator Lots: 3 lots of reagents were used.
- Calibrator Samples: Lumipulse G Progesterone-N Calibrator 1 and Calibrator 2 were tested in duplicate at each time point for sensitivity.
- Serum Samples (for accuracy and reproducibility): 3 serum samples (concentrations: 3.15 - 24.42 ng/mL) were tested in replicates of 6 at each time point.
- Data Provenance: Fujirebio, Inc. (Tokyo, Japan) and Fujirebio Diagnostics, Inc. (Malvern, PA). The studies are prospective in nature, as they involve monitoring stability over time.
- Value Assignment:
- Replicates for provisional value: 6 replicates for initially assigned provisional value.
- Replicates for assigned value: 10 replicates for primary calibrators and original calibrators over 3 runs on LUMIPULSE G.
- Data Provenance: Implied to be internal studies at Fujirebio.
- Transport Simulation (Tokyo):
- Specific sample count not provided beyond "the concentration of the panel replicates were determined."
- Data Provenance: Fujirebio, Inc. (Tokyo, Japan).
- Transport Simulation (Malvern):
- Calibrators were tested in duplicate, controls in singlicate, and panels in triplicate.
- Data Provenance: Fujirebio Diagnostics, Inc. (Malvern, PA).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
- Not Applicable. For a calibrator, the "ground truth" is established through highly controlled gravimetric preparations and traceability to international reference materials (ERM-DA347 and BCR-348R). This process does not involve human experts in the typical sense of interpreting diagnostic images or clinical outcomes. The "experts" would be analytical chemists or metrologists defining the concentration of the progesterone standard.
4. Adjudication Method for the Test Set
- Not Applicable. Adjudication methods like 2+1 or 3+1 are used in clinical studies involving interpretation of results by multiple human readers (e.g., radiologists, pathologists). This document describes the analytical performance and stability of a calibrator, which involves quantitative measurements against predefined criteria, not human interpretation.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
- No. MRMC studies are used to evaluate the impact of a diagnostic device (often AI-based) on human reader performance. This document concerns a calibrator, which is a component used in an in vitro diagnostic assay, not a diagnostic algorithm that assists human interpretation.
6. If a Standalone (Algorithm Only) Performance Study was Done
- No. This is not an AI algorithm. The device is a calibrator for an in vitro diagnostic test system (LUMIPULSE G System). The performance studies presented are for the calibrator's stability and accuracy in establishing known concentrations for the assay.
7. The Type of Ground Truth Used
The ground truth for the Progesterone-N Calibrators is established through:
- Metrological Traceability: Directly linked to internationally recognized reference materials (ERM-DA347 and BCR-348R by IRMM).
- Gravimetric Preparation: The calibrators are prepared by precise weighing of progesterone, ≥ 99%, from SIGMA-ALDRICH, dissolved in ethanol and spiked into a buffer.
- Assigned Values: The values are assigned based on measurements on the LUMIPULSE G system, cross-referenced with gravimetrically prepared stock solutions and ensuring the "mean ratio" (of primary to original calibrators) falls within an acceptable range (0.95 - 1.05).
8. The Sample Size for the Training Set
- Not Applicable. This is not an AI/ML device that requires a training set. The performance data relates to the physical and chemical properties of the calibrator itself.
9. How the Ground Truth for the Training Set Was Established
- Not Applicable. As there is no training set for an AI/ML algorithm, this question is not relevant.
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.