(23 days)
Clinical Chemistry - The Sentinel Plasmaproteins Cal 3x is a device intended for medical purposes for use in Ceruloplasmin, Kappa light chains, Lambda light chains, Transferrin, Alpha 1-Acid Glycoprotein, Alpha 1-Antitrypsin, Haptoglobin, Immunoglobulin A, Immunoglobulin G and Immunoglobulin M assays, to establish points of reference that are used in the determination of values in the measurement of Ceruloplasmin, Kappa light chains, Lambda light chains, Transferrin, Alpha 1-Acid 1 - Antitrypsin, Glycoprotein, Alpha Haptoglobin, Immunoglobulin A, Immunoglobulin G and Immunoglobulin M in human serum and plasma.
Sentinel Plasmaproteins Cal 3x must only be used for the calibration of plasmaprotein tests with the immunoturbidimetric methods.
The Sentinel Plasmaproteins Cal 3x is a liquid, ready-to-use calibrator prepared from plasmatic plasmaproteins in human-based serum. It consists of 4 x 1 mL bottles of aqueous material containing Ceruloplasmin, Kappa light chains, Lambda light chains, Transferrin, Alpha 1-Acid Glycoprotein, Alpha 1-Antitypsin, Haptoglobin, Immunoglobulin A, Immunoglobulin G and Immunoglobulin M in a human serum matrix. This material, when stored as directed, is stable until the date printed on the label. Calibrator traceability was stated as certificated to CRM 470 (Certified Reference Material), renamed ERM-DA 470 (European Reference Materials).
This looks like a submission for an In Vitro Diagnostic (IVD) device, specifically a calibrator for plasmaprotein assays. The provided text describes the device and its modifications, not a study evaluating an AI-powered diagnostic device in the traditional sense (e.g., image-based diagnosis). Therefore, many of the requested elements for an AI study (like sample size for test set, number of experts, adjudication method, MRMC study, standalone performance, ground truth for training set, etc.) are not applicable to this type of submission.
However, I can extract the relevant information regarding the acceptance criteria and the "study" (validation process) for this calibrator to demonstrate its substantial equivalence.
Here's the information based on the provided text, with clarifications where the requested AI study elements do not apply:
Acceptance Criteria and Device Performance for Sentinel Plasmaproteins Cal 3X
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Sentinel Plasmaproteins Cal 3x calibrator relate to the expected range for the target values of each analyte when calibrated. The "reported device performance" is essentially the determination that the calibrated values fall within these specified ranges after the validation process.
| Analyte | Acceptance Criteria (Target Value Range) (mg/dL) | Reported Device Performance (Implied: Within Range) |
|---|---|---|
| alpha 1-Acid Glycoprotein | From 176 to 254 | Within Range |
| Albumin | From 9344 to 14016 | Within Range |
| Alpha 1-Antitrypsin | From 334 to 454 | Within Range |
| Ceruloplasmin | From 66 to 124 | Within Range |
| Haptoglobin | From 272 to 366 | Within Range |
| Immunoglobulin A | From 478 to 718 | Within Range |
| Immunoglobulin G | From 2264 to 3396 | Within Range |
| Immunoglobulin M | From 204 to 3396 | Within Range |
| Kappa | From 508 to 762 | Within Range |
| Lambda | From 306 to 458 | Within Range |
| Transferrin | From 580 to 872 | Within Range |
Additional Performance Criteria for Accepting a Single Run:
- Results of normal and abnormal approved control materials are within the expected ranges.
- The % recovery of Internal Calibrator Master Lot is within 97% - 103%.
Criteria for Target Value Determination:
- Absence of outliers (single data - Mean > 3SD).
- Imprecision less than 5%.
- The obtained mean must be the Target value.
2. Sample Size Used for the Test Set and Data Provenance
This is an IVD calibrator, not an AI diagnostic device that uses a "test set" of patient data in the typical sense.
- Sample Size for Testing: For the validation of the calibrator, aliquots of the Plasmaproteins Cal 3x to be tested were analyzed in triplicate during each testing run. For each analyte, three (3) analytical runs were performed on at least two (2) different days.
- Data Provenance: The calibrator is prepared from plasmatic plasmaproteins in human-based serum. The exact country of origin for the human serum is not specified, but the submission is from Milan, Italy. The testing described is prospective, as it involves laboratory analysis of the manufactured calibrator.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This is not applicable as this is an IVD calibrator. "Ground truth" for this device refers to the certified reference materials and established laboratory methods used to assign values to the calibrator, not expert consensus on medical images or patient outcomes. The traceability of the calibrator was stated as certificated to CRM 470 (Certified Reference Material), renamed ERM-DA 470 (European Reference Materials), which represents a highly standardized "ground truth" for analytical measurements.
4. Adjudication Method for the Test Set
Not applicable for an IVD calibrator. The "adjudication" is based on adherence to established quality control ranges, % recovery of internal calibrators, and statistical checks for outliers and imprecision as described in point 1.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. This type of study is not relevant for an IVD calibrator. The submission focuses on demonstrating substantial equivalence to predicate calibrators and validating the assigned values through laboratory testing.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
While the device itself operates without human intervention once the assays are set up, the concept of "standalone performance" as typically applied to AI algorithms (i.e., algorithm only without human interaction) is not applicable here. The device is a calibrator, which is a component in a larger analytical process; its performance is intrinsically linked to the assays and instruments it calibrates. The "standalone" aspect would be its ability to consistently provide accurate reference points.
7. The Type of Ground Truth Used
The ground truth for the analyte values in the calibrator is established by traceability to certificated reference materials (CRM 470 / ERM-DA 470), which provides highly accurate and internationally recognized standards for the quantification of these plasma proteins. This is complemented by an "Internal Calibrator Master Lot" used in the calibration process.
8. The Sample Size for the Training Set
Not applicable. This is an IVD calibrator, not an AI algorithm that undergoes "training." The "training" of the analytical process would involve setting up and validating the immunoturbidimetric assays on specific instruments according to manufacturer protocols, using the reference materials.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As above, this is an IVD calibrator. The "ground truth" for the overall analytical process (which the calibrator is a part of) is established through certified reference materials and validated immunoassay methodologies. The target value assignment procedure for the calibrator itself is described as being in internal SOPs and under defined conditions, utilizing the mentioned CRMs and an Internal Calibrator Master Lot.
§ 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.