(25 days)
For in vitro diagnostic use only.
For use in the calibration of the VITROS ECVECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System for the quantitative measurement of insulin in human serum and plasma (Li Heparin).
The VITROS® Immunodiagnostic Products Insulin Calibrators contain three levels of calibrator, Calibrator 1, 2, 3. Nominal values are 1 uIU/mL, 25 µIU/mL and 250 µIU/mL respectively. The calibrators are liquid and comprised of recombinant human insulin in buffer containing BSA with an antimicrobial agent. VITROS® Immunodiagnostic Products Insulin Calibrators kit contains 1 vial of each calibrator 1, 2, and 3. Each vial contains 1mL of calibrator.
This document is a 510(k) Premarket Notification from Ortho-Clinical Diagnostics, Inc. to the FDA regarding their VITROS® Immunodiagnostic Products Insulin Calibrators. It aims to demonstrate substantial equivalence to a legally marketed predicate device.
Based on the provided text, the device in question is a calibrator for in vitro diagnostic use, not an AI-powered medical device for image analysis or disease detection. Therefore, the questions related to AI performance metrics (like sensitivity, specificity, MRMC studies, human reader improvement with AI assistance, ground truth establishment for AI training sets, etc.) are not applicable to this submission.
The acceptance criteria and performance data for this type of device (a calibrator) typically revolve around analytical performance characteristics such as:
- Stability: How long the calibrator remains effective under different storage conditions (unopened shelf-life, opened on-board stability).
- Traceability: Ensuring the values assigned to the calibrators are linked to a recognized international standard.
- Value Assignment: The process by which the calibrator values are accurately determined.
Here's how the provided document addresses these aspects:
1. A table of acceptance criteria and the reported device performance
The document does not present a formal table of acceptance criteria with corresponding performance results in the way one would for an AI-powered diagnostic device (e.g., sensitivity/specificity targets). Instead, it discusses the studies and principles related to the calibrator's performance.
Acceptance Criteria (Implied for a Calibrator):
- Shelf-life: The calibrators must maintain their stated values and functionality for a specific duration when stored unopened.
- Opened Stability: The calibrators must maintain their stated values and functionality for a specific duration after being opened and placed on the instrument.
- Traceability: The assigned values must be traceable to an internationally recognized standard.
- Value Assignment Accuracy: The process for assigning values must be robust and accurate, ensuring reliable calibration curves.
Reported Device Performance (as described in the text):
- Unopened Stability: "Shelf-life of the VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study. The final shelf life claim will be based on the completed real time study results." (This indicates a study is ongoing/planned to establish the shelf-life, not that a final claim is being made in this report).
- Opened Stability: "Storage life for open vials of VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study and will support the open off board shelf life statement in the Instructions for Use." (Similar to unopened stability, the study is planned/ongoing).
- Traceability: "Values assigned to the VITROS Immunodiagnostic Products Insulin Calibrators are traceable to the WHO 1st International Reference Preparation 66/304."
- Value Assignment: "The Value assignment process transfers the calibration from the WHO Standard (66/304) to reference standards and then to calibrators used by the end user to establish a valid calibration curve on the VITROS ECi/ECiQ Immunodiagnostic Systems, the VITROS 3600 Immunodiagnostic System and the VITROS 5600 Integrated System."
Summary of Stability (from page 6):
- Unopened: "Store at 2-8°C until expiration date"
- Opened: "13 weeks"
- Note: This appears in the "Comparison with Predicate - Differences" table (page 5), suggesting these are the claims for the new device, and the "Summary of Stability" on page 6 refers to the studies being conducted to support these claims, or previous studies that led to these claims. For the predicate device, opened stability is "Store at 2-8°C until expiration date."
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)
The term "test set" in the context of AI models is not directly applicable here. For a calibrator, the "test set" would typically refer to the samples used in stability studies. The document states:
- "Shelf-life of the VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study."
- "Storage life for open vials of VITROS Immunodiagnostic Products Insulin Calibrators will be determined by a real time stability study."
Details on the sample sizes (e.g., number of calibrator lots, number of measurements per time point) or data provenance (country of origin) for these stability studies are not provided in this summary. The studies are described as "real time," indicating they are prospective studies.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)
As this is a calibrator, "ground truth" is established via traceability to an internationally recognized reference preparation, not through human expert interpretation. The document states:
- "Values assigned to the VITROS Immunodiagnostic Products Insulin Calibrators are traceable to the WHO 1st International Reference Preparation 66/304."
Therefore, human experts are not applicable for establishing "ground truth" in this context.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not applicable. Adjudication methods are used in studies involving human interpretation or challenging diagnostic cases. For a calibrator, performance is assessed through analytical measurements and traceability, not through human adjudication of results.
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. This device is a calibrator, not an AI-powered diagnostic tool, and involves no human readers or image interpretation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This device is a physical calibrator reagent, not an algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the calibrator's value assignment is based on traceability to a recognized international reference standard: "WHO 1st International Reference Preparation 66/304." This is a metrological ground truth for analytical measurement.
8. The sample size for the training set
Not applicable. As this is a calibrator for in vitro diagnostics, not a machine learning model, there is no "training set" in the AI sense. Calibration involves a direct measurement comparison against a reference, not a data-driven learning process.
9. How the ground truth for the training set was established
Not applicable. See point 8.
§ 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.