(25 days)
C.f.a.s. (Calibrator for automated systems) PAC (Prealbumin-ASLO-Ceruloplasmin) is for use in the calibration of quantitative Roche methods on Roche clinical chemistry analyzers as specified in the value sheets.
C.f.a.s. (Calibrator for automated systems) Proteins is for use in the calibration of quantitative Roche methods on Roche clinical chemistry analyzers as specified in the value sheets.
PreciControl ClinChem Multi 1 is for the use in quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheets. PreciControl ClinChem Multi 2 is for the use in quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheets.
Precinorm Protein and Precipath Protein are for the use in quality control by monitoring accuracy and precision for the quantitative methods as specified in the value sheets.
C.f.a.s. Proteins is a liquid ready-to-use calibrator based on human serum. The concentrations of the components have been adjusted to ensure optimal calibration of the appropriate Roche methods on clinical chemistry analyzers.
C.f.a.s. PAC is a lyophilized calibrator based on human serum. The concentrations of the components have been adjusted to ensure optimal calibration of the appropriate Roche methods on clinical chemistry analyzers.
PreciControl ClinChem Multi 1 and 2 are lyophilized controls based on human serum. The adjusted concentrations and activities of the components of PCCC Multi 1 are usually in the normal range or at the normal/pathological threshold. The adjusted concentrations and activities of the components of PCCC Multi 2 are usually in the pathological range.
Precinorm Protein and Precipath Protein are liquid ready-for-use control sera based on human serum. The concentrations of the components of Precinorm Protein are usually in the normal range or at the normal/pathological threshold. The concentrations of the components of Precipath Protein are usually in the pathological range.
Below is a summary of the acceptance criteria and study information for the device based on the provided text.
1. Acceptance Criteria and Reported Device Performance
The study evaluates the impact of "device modifications" on the performance of four in-vitro diagnostic devices (calibrators and control sets). The modifications primarily involve changing the Antistreptolysin O (ASLO) analyte source material from human serum to sheep serum, and some biological additive changes for C.f.a.s. PAC and PCCC.
The performance characteristics assessed are:
- Stability: Shelf life and open vial stability.
- Method Comparison: Comparison of ASLO measurements between the candidate and predicate C.f.a.s. PAC calibrators.
- Lower Detection Limit (LDL): Verification of ASLO LDL.
- Control Recovery: Evaluation of ASLO control recovery using the modified control sets.
- Precision: Assessment of ASLO and Ferritin precision.
| Test Category | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Stability (General) | Averaged results must be 90% to 110% recovery of the reference value for C.f.a.s. Proteins, C.f.a.s. PAC, PCCC, PNP, and PPP. | Results from all analytes from all four devices range from 91 to 108% recovery, meeting the criterion. The open vial stability claims appear in the device package inserts and are supported. The unopened stability claim, or shelf life claim, is supported by the new data. |
| Stability (PNP/PPP ASLO) | The average results must be 85% to 115% recovery of the reference value for Antistreptolysin O in PNP/PPP. | Included in the general stability results above (91-108% recovery), indicating it also met this specific criterion. |
| Method Comparison (ASLO - c 501) | Slope = 1.00 ± 0.10, Intercept ≤ ± 20 IU/mL, R value ≥ 0.975 (for ASLOT c 501). | Slope = 1.00, Intercept = -2 IU/mL, R value = 0.998. This meets the criteria. |
| Method Comparison (ASLO - INTEGRA 800) | Implicitly the same criteria as c 501 for slope, intercept, and R value, or similar tight correlation. (The table for INTEGRA 800 only explicitly shows results, implying similar criteria for acceptance of "compare well"). | Slope = 1.00, Intercept = 0 IU/mL, R value = 1.000. This meets the criteria. |
| Lower Detection Limit (LDL) - ASLO | LDL claim of ≤ 20 IU/mL. | The study showed an LDL of 2 IU/mL, which meets the criterion. |
| Control Recovery (ASLO) | 90% to 110% recovery of the target value. | Results range from 97 to 104% recovery of the target value. All values meet the acceptance criterion. |
| Precision (ASLO) | CV ≤ 4%. | ASLO precision results range from 0 to 2% CV. All results meet the criterion. |
| Precision (Ferritin) | CV ≤ 5%. | Ferritin precision results range from 0 to 2% CV. All results meet the criterion. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size:
- Method Comparison (ASLO): "a data set of human serum samples." The specific number of samples is not provided, but it states "human serum samples."
- Lower Detection Limit (ASLO): n = 21 replicates for the calculation.
- Precision (ASLO and Ferritin): 21 replicates were measured in a single run in a single day for each test system (total 2 test systems for ASLO, 1 for Ferritin).
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the context of submitting to the FDA, it is likely that the data was generated in a controlled, prospective manner following industry standards for manufacturing and testing of in-vitro diagnostics. The materials (calibrators and controls) are for use with Roche clinical chemistry analyzers (Roche/Hitachi and COBAS INTEGRA families), which are widely available globally. The source of some materials changed FROM "human" TO "sheep," but the "human serum samples" used for method comparison are not detailed as to their origin.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This is a study for in-vitro diagnostic calibrators and controls, not an imaging device or a diagnostic algorithm requiring expert interpretation of results to establish ground truth. The "ground truth" here refers to reference values established through traceable methods and master lots, and the comparison is based on quantitative analytical performance against these established reference values.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. As this is not a study involving human readers or subjective interpretations, no adjudication method was used. Performance is assessed against quantitative analytical criteria.
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. No MRMC study was conducted as this device is an in-vitro diagnostic calibrator/control, not an AI-assisted diagnostic tool.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance evaluation was done in the sense that the analytical performance of the modified calibrators and controls was tested directly on analyzers (cobas c 501 and INTEGRA 800) against predefined quantitative criteria. There is no "human-in-the-loop" component in the direct measurement and assessment of these IVD devices for their intended use (calibration and quality control).
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth used for performance evaluation is based on reference values established through traceable master lots and reference methods. For calibrators, value assignment is "traceable through master lot to reference methods or materials." For controls, "target values" are used, and analytical results are compared to these target values to determine recovery. In the context of lab diagnostics, this is the accepted standard for defining "ground truth" or reference for quantitative measurements.
8. The sample size for the training set
Not applicable for this type of IVD device modification submission. This is not an AI/machine learning device that requires a training set. The "training" in this context would refer to the historical data and method development that led to the predicate devices and the current testing methodologies, rather than a distinct "training set" for an algorithm.
9. How the ground truth for the training set was established
Not applicable, as there is no training set in the context of AI/ML. The reference values for calibrators and control materials are established through rigorous analytical measurement processes, often involving comparison to international reference materials or highly accurate reference methods, and internal master lot value assignment protocols.
§ 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.