(63 days)
The Audit™ MicroCV™ Therapeutic Drug (TDM) Linearity Set consists of five levels in Human and Bovine serum albumin matrix. Each level contains the following analytes: Acetaminophen, Amikacin, Carbamazepine, Digoxin, Gentamicin, Methotrexate, Phenobarbital, Phenytoin, Quinidine, Salicylate, Theophylline, Tobramycin, Valoroic Acid and Vancomycin. The five levels demonstrate a linear relationship to each other for their respective analytes, reagents, and instruments.
This product may be used for proficiency testing in interlaboratory surveys and to perform CLIA directed calibration verification for these same analytes with similar reagents on similar instrumentation in accordance with current CLIA-88 guidelines and regulations.
In addition, Level A – E of this product may be used as unassayed quality control material for these analytes or as an assayed quality control material for the analyzer systems specified in the package insert. It is not intended to be used as an assayed quality control material for any other analyzer systems.
The Audit™ MicroCV™ Therapeutic Drug (TDM) Linearity Set is a human based, lyophilized, five level set of QC material, with each level containing 14 analytes. It is used to confirm the proper calibration, linear operating range, and reportable range of Therapeutic Drug (TDM) methods for the analytes listed. Level A is near the lower limit level and Level E has concentrations near the upper limit of instruments. Levels B -- D are related by linear dilution of Level A and Level E.
The provided text is a 510(k) Summary for a Quality Control Material (QCM), specifically the Audit™ MicroCV™ Therapeutic Drug (TDM) Linearity Set. Devices of this type are not typically evaluated with the extensive criteria common for diagnostic AI algorithms (e.g., performance metrics like sensitivity, specificity, or ROC curves against a ground truth from experts). Instead, the assessment focuses on their characteristics matching their intended use as QCMs, primarily stability and linearity, and their substantial equivalence to a predicate device.
Therefore, many of the requested categories in your prompt are not applicable or directly derivable from this type of regulatory submission. I will address the relevant information that can be extracted.
Not Applicable (N/A) Categories for this type of device and submission:
- Sample size used for the test set and the data provenance: Not applicable. Performance for QCMs is typically demonstrated through characteristics like stability and linearity, not by processing a "test set" of patient data in the way an AI algorithm would.
- Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. Ground truth for AI algorithms involves expert interpretation; for QCMs, it's about analytical performance.
- Adjudication method (e.g., 2+1, 3+1, none) for the test set: Not applicable.
- If a multi reader multi case (MRMC) comparative effectiveness study was done: Not applicable.
- If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: Not applicable, as this is a physical control material, not an algorithm.
- The type of ground truth used (expert consensus, pathology, outcomes data, etc.): For a QCM, "ground truth" relates to the expected values and behavior of the reference material itself, established through analytical methods and manufacturing processes, not expert medical opinion on a patient.
- The sample size for the training set: Not applicable, as this is not an AI algorithm.
- How the ground truth for the training set was established: Not applicable.
Relevant Information and Acceptance Criteria for the Audit™ MicroCV™ Therapeutic Drug (TDM) Linearity Set:
The device's performance is primarily demonstrated by its stability and its ability to establish a linear relationship for the specified analytes. Its acceptance criteria are implicitly tied to maintaining these characteristics over time. The "study" mentioned refers to internal stability studies.
1. Table of Acceptance Criteria and the Reported Device Performance
| Acceptance Criteria Category | Specific Acceptance Criteria (Implicit) | Reported Device Performance/Characteristics |
|---|---|---|
| Intended Use Fulfillment | The device should "simulate human patient serum samples for the purpose of verifying and validating the Analytical Measurement Range for non-waived Therapeutic Drug (TDM) testing methods as identified in the package insert." It should also allow for "proficiency testing" and "CLIA directed calibration verification." | - Consists of a human based, lyophilized, five-level set of QC material. |
- Each level contains 14 analytes (Acetaminophen, Amikacin, Carbamazepine, Digoxin, Gentamicin, Methotrexate, Phenobarbital, Phenytoin, Quinidine, Salicylate, Theophylline, Tobramycin, Valoroic Acid and Vancomycin).
- The five levels "demonstrate a linear relationship to each other for their respective analytes, reagents, and instruments." |
| Reconstituted Stability | Maintain analyte stability for a specified period after reconstitution when stored under defined conditions. | 5 days when stored tightly capped at 2 - 8° C. |
| Shelf Life | Maintain stability for a specified period when stored unopened under defined conditions. | Two years when stored unopened at 2 - 8° C. (Note: Real-time studies are ongoing to support this claim). |
| Linearity | The five levels (A-E) should demonstrate a linear relationship for the specified analytes. | Levels A-E "demonstrate a linear relationship to each other for their respective analytes, reagents, and instruments." Levels B-D are related by linear dilution of Level A and Level E. |
2. Data Provenance for Performance Evaluation:
- Test Set (for performance demonstration of stability and linearity): The document states "All supporting data is retained on file at Aalto Scientific, Ltd." This implies the data originates from internal studies conducted by the manufacturer.
- Country of Origin: United States (Aalto Scientific, Ltd. is located in Carlsbad, CA).
- Retrospective or Prospective: Stability studies are typically prospective, meaning the product is manufactured and then monitored over time according to a predefined protocol. Linearity verification would also be a prospective test using the manufactured material.
3. Study Proving Acceptance Criteria:
The document explicitly mentions:
- "Stability studies have been performed to determine the reconstituted stability and shelf life for the Audit™ MicroCV™ Therapeutic Drug (TDM) Linearity Set."
- These studies prove the device meets the Reconstituted Stability and Shelf Life acceptance criteria.
- The "linear relationship" of the five levels is a fundamental characteristic of the device's design and is presumably verified during development and quality control testing, fulfilling the Linearity criterion.
6. Standalone Performance:
Yes, the performance claims (stability, linearity for TDM methods) are for the algorithm/device only, in the sense that the physical control material itself has these properties, independent of human interpretation or assistance in its function as a control. It is a standalone diagnostic reagent used to evaluate other analytical systems.
9. How the Ground Truth for the Training Set (or rather, the Reference Values for the QCM) was Established:
While there is no "training set" in the AI sense, the concentrations and intended linear relationship of the analytes within the QCM are established during its manufacturing process. This involves:
- Formulation and Dilution: Levels B-D are created by linear dilution of Level A and Level E. This precise formulation establishes the expected "linear ground truth" for calibration verification.
- Master Lot Testing/Value Assignment: For quality control materials, reference methods and/or highly characterized instruments are used to assign target values to each analyte in each level. This process establishes the expected 'ground truth' values against which user instruments can be calibrated and verified. The document does not detail this specific process but it is standard for QCM manufacturing.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.