(210 days)
The PATHFAST® CK-MB-11 Calibrators are for calibration of the PATHFAST® system when used for the quantitative determination of creatine kinase-MB in human heparinized or EDTA whole blood and plasma.
The PATHFAST CK-MB-II Calibrators are used for calibration of the PATHFAST CK-MB-11 test performed on the PATHFAST instrument. PATHFAST CK-MB-II test is an in vitro diagnostic test for the quantitative measurement of creatine kinase-MB in heparinized or EDTA whole blood and plasma. Currently, PATHAST CK-MB-II Calibrators 1 and 2 are provided as lyophilized products of two vials each. Calibrator 1 consists of saline and a preservative, and Calibrator 2 consists of CK-MB in buffer. Four vials of calibrator diluent also are provided for reconstitution of the calibrators. The diluent consists of an aqueous solution with 0.05% sodium azide. This Special 510(k) is being submitted for a change to a liquid Calibrator 1 formulation and a new dropper bottle container. There are no changes to PATHFAST CK-MB-11 Calibrator 2. As a result of elimination of the reconstitution step for PATHFAST CK-MB-II Calibrator I, the number of bottles of Calibrator Diluent is being reduced from four bottles to two bottles.
The provided document is a 510(k) summary for a PATHFAST® CK-MB-II Calibrator 1, which is a medical device used for the calibration of a system that measures creatine kinase-MB. The 510(k) is a Special 510(k), indicating a modification to an already cleared device, not a new device submission.
The core of this submission is to demonstrate substantial equivalence between a new liquid formulation of Calibrator 1 and its previously cleared lyophilized format. Therefore, the "device performance" in question relates to how well the new formulation maintains the established performance characteristics of the calibrator, rather than the diagnostic performance of the CK-MB-II test itself.
Here's an analysis based on your questions:
1. Table of Acceptance Criteria and Reported Device Performance:
The document broadly states that the modified calibrator met "all pre-established acceptance criteria." However, it does not provide a specific table or detailed quantitative acceptance criteria for each study. It lists the types of studies performed and implies that their results validated the change.
| Study Type | Reported Device Performance | Acceptance Criteria (Not Explicitly Stated in Document) |
|---|---|---|
| Assay Sensitivity | Met acceptance criteria | Implied: The modified calibrator allows the PATHFAST system to achieve the same sensitivity for CK-MB-II as with the original calibrator. This would likely involve specific limits on detection or quantification of low analyte concentrations. |
| Limit of Blank (LoB) | Met acceptance criteria | Implied: The LoB for the system, when calibrated with the modified calibrator, falls within acceptable predefined limits. This defines the highest measurement result that is likely to be observed for a blank sample. |
| Limit of Detection (LoD) | Met acceptance criteria | Implied: The LoD for the system, when calibrated with the modified calibrator, falls within acceptable predefined limits. This defines the lowest concentration of analyte that can be reliably detected. |
| Limit of Quantitation (LoQ) | Met acceptance criteria | Implied: The LoQ for the system, when calibrated with the modified calibrator, falls within acceptable predefined limits. This defines the lowest concentration of analyte that can be reliably quantified with acceptable accuracy and precision. |
| Accuracy | Met acceptance criteria | Implied: The modified calibrator allows the PATHFAST system to provide accurate CK-MB-II measurements, comparable to those obtained with the original calibrator. This would likely be assessed against reference materials or established methods. |
| Method Comparison | Met acceptance criteria | Implied: Results obtained using the PATHFAST system calibrated with the modified liquid calibrator are statistically comparable to results obtained with the system calibrated with the predicate lyophilized calibrator. This often involves correlation coefficients, bias, and agreement studies. |
| Matrix Comparison | Met acceptance criteria | Implied: The performance of the modified calibrator is consistent across different sample matrices (e.g., heparinized whole blood, EDTA whole blood, plasma), demonstrating no significant matrix effects. |
| Precision | Met acceptance criteria | Implied: The modified calibrator allows the PATHFAST system to maintain the same level of precision (reproducibility and repeatability) for CK-MB-II measurements as with the original calibrator. This would involve assessment of within-run, between-run, and total precision with specific CV% limits. |
| Real-time Stability | Met acceptance criteria | Implied: The liquid calibrator maintains its specified performance characteristics (e.g., CK-MB concentration, physical properties) over its labelled shelf-life under specified storage conditions. Specific stability protocols and acceptance limits (e.g., % change from initial value) would be defined. |
| Elution | Met acceptance criteria | Implied: No significant chemical substances leach from the new polypropylene dropper bottle container into the calibrator solution, which could interfere with the assay or affect calibrator stability. Acceptance criteria would likely involve limits on detected leachables or demonstration of no assay interference. |
| Evaporation | Met acceptance criteria | Implied: The new polypropylene dropper bottle container adequately prevents evaporation of the calibrator solution over its specified shelf-life, ensuring the concentration remains stable. Acceptance criteria would involve limits on weight loss or concentration change due to evaporation. |
2. Sample Size Used for the Test Set and Data Provenance:
The document does not specify the sample sizes used for the test sets in any of the validation/verification studies (e.g., for sensitivity, accuracy, method comparison, stability, etc.).
It also does not directly state the data provenance (e.g., country of origin of the data, retrospective or prospective). Given that the submitting company is "Mitsubishi Chemical Medience Corporation" in "Tokyo, 108-8559 Japan," it is highly probable that the studies were conducted in Japan, but this is not explicitly stated. The studies are described as "validation/verifications studies were performed" which implies prospective testing as part of the design control system for the modified product.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
This question is not applicable to this type of device submission. This document pertains to a calibrator, which is a reagent used to standardize a diagnostic test. The ground truth for a calibrator's performance is typically established through analytical laboratory methods and metrological traceability, not through expert interpretation of images or patient data. The "ground truth" for the calibrator's value would be its assigned concentration based on primary calibrators and validated methods within a quality system, not an expert consensus.
4. Adjudication Method for the Test Set:
This question is not applicable as there is no mention or implication of expert adjudication in the context of validating a calibrator. The validation involves analytical measurements and comparisons against established methods and 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:
This question is not applicable. An MRMC study is relevant for evaluating the performance of diagnostic imaging aids or AI algorithms that assist human readers in interpreting clinical data. This submission is for a laboratory calibrator, which does not involve human readers interpreting cases or AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
This question is not applicable. There is no AI algorithm involved in this device (a calibrator). The device's performance is intrinsically standalone in an analytical sense, as it is a chemical reagent, but it's not an "algorithm" operating independently.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):
The "ground truth" for a calibrator like PATHFAST CK-MB-II CALIBRATOR 1 is the analytically assigned value for the analyte concentration (in this case, 0 ng/mL for Calibrator 1, which provides a zero analyte level for the calibration curve). This ground truth is established through:
- Primary calibrators and reference materials: Ensuring metrological traceability to international standards if available.
- Validated analytical methods: Using highly accurate and precise laboratory techniques to assign the value.
- Internal quality control systems: To ensure consistency and accuracy of value assignment.
The document states, "CK-MB concentration = 0 ng/mL. Provides zero analyte level for user calibration curve" for the "Fundamental Scientific Technology" and "Value Assignment" involves "Primary calibrator, master calibrator, stock solution, working calibrator." This indicates an analytical ground truth based on traceable reference materials and meticulous value assignment procedures.
8. The Sample Size for the Training Set:
This question is not applicable. This device is a calibrator, not a machine learning model. Therefore, there is no "training set" in the context of AI or algorithm development. The validation studies performed assess the analytical performance of the calibrator itself.
9. How the Ground Truth for the Training Set was Established:
This question is not applicable for the same reason as point 8; there is no training set for a calibrator.
§ 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.