(78 days)
The Audit® MicroControls™ Linearity FD Tumor Markers II is intended to simulate human patient samples for use as assayed quality control material, determining linearity, callbration verification of reportable range for the HE4 and HER2 analytes.
The Audit® MicroControlsTM Linearity FD Tumor Markers II is for In Vitro Diagnostic use only.
The Audit® MicroControls™ Linearity FD Tumor Markers II is an in-vitro diagnostic device consisting of sets of 5 levels of freeze-dried, linearity material and additives in human based serum. The product contains the following analytes: HE4 and HER2. Each set consists of 5 levels labeled Level A, B, C, D and E. Each level has a fill size of 1ml. Materials of human origin used in the manufacture of this linearity set have been tested using FDA approved methods and are found to be non-reactive for HbsAg and antibodies to HCV and HIV-1/2.
This document describes the Audit® MicroControls™ Linearity FD Tumor Markers II, an in-vitro diagnostic device. The provided text, however, focuses on the substantial equivalence review for a regulatory submission (510(k)) and details the device's characteristics, intended use, and performance data from stability studies. It does not present a study designed to prove the device meets specific acceptance criteria in terms of diagnostic accuracy or clinical effectiveness, as it is a quality control material.
The "acceptance criteria" discussed here relate to the stability and value assignment of the control material, not to diagnostic performance metrics like sensitivity or specificity for a medical imaging device. The "performance" refers to the stability of the control material and its ability to provide target values.
Therefore, many of the requested points are not applicable to this type of device and submission. I will address the relevant points based on the provided text.
Acceptance Criteria and Reported Device Performance
As this device is a quality control material, the acceptance criteria relate to its stability and the establishment of target values for its analytes (HE4 and HER2).
| Acceptance Criteria Category | Specific Criteria/Study Type | Reported Device Performance/Findings |
|---|---|---|
| Shelf Life Stability | Accelerated Stability Study: To establish a claimed shelf life. (Specific numerical criteria for % deviation or other metrics are not provided in this summary but are stated as "Acceptance criteria were met to support the product claims.") | Shelf Life: 2 years, when stored unopened at 2-8º C. (Supported by accelerated stability studies; real-time studies are ongoing.) |
| Open Vial Stability | Real-Time Stability Study: To establish a claimed open vial stability period. (Specific numerical criteria for % deviation or other metrics are not provided in this summary but are stated as "Acceptance criteria were met to support the product claims.") | Open Vial Stability: 7 days, when stored tightly capped at 2-8º C. (Supported by real-time stability studies.) |
| Value Assignment | Multiple Measurements: Each analyte at each level was measured multiple times to establish mean target concentration values. | HE4/Roche Cobas e411 (pmol/L) Target Values and Ranges: |
| Level A: 20.5 (Range 16.4-24.6) | ||
| Level B: 380.6 (Range 304.5-456.7) | ||
| Level C: 783.9 (Range 627.1-940.7) | ||
| Level D: 1217.8 (Range 974.2-1461.4) | ||
| Level E: 1461.0 (Range 1168.8-1753.2) |
HER2/Siemens Centaur XP (ng/ml) Target Values and Ranges:
Level A: 5.1 (Range 4.1-6.1)
Level B: 74.0 (Range 59.2-88.8)
Level C: 146.0 (Range 116.8-175.2)
Level D: 241.3 (Range 193.1-289.6)
Level E: 303.0 (Range 242.4-363.7) |
| Linearity (expected) | The "Levels B, C and D produced according to the following dilution scheme:" suggests that the material is designed to demonstrate a linear relationship between levels. | The dilution scheme is provided:
Level B = 0.75(Level A) + 0.25(Level E)
Level C = 0.5(Level A) + 0.5(Level E)
Level D = 0.25(Level A) + 0.75(Level E) |
Additional Information based on request:
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Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Test Set Sample Size: Not explicitly stated in terms of number of distinct samples for the stability studies or value assignment. The studies involved analyzing "vials representative of the entire lot" and "multiple times" for value assignment.
- Data Provenance: The studies were conducted by Aalto Scientific, Ltd. in Eatonton, GA, USA. The data would be considered prospective for the stability studies. The origin of the human serum matrix is not specified beyond "human serum."
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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)
- Not Applicable. The "ground truth" for this device refers to the assigned target values and stability characteristics of the quality control material itself, determined through laboratory measurements, not human expert interpretation of clinical data.
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Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Not Applicable. This is not a study requiring adjudication of diagnostic interpretations. The value assignment was based on "mean value" from "multiple measurements" using specific laboratory analyzers and reagents.
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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 is a quality control material, not an AI diagnostic device that assists human readers.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not Applicable. This is a quality control material. However, the performance assessment of the control material (stability, value assignment) is done in a "standalone" laboratory setting by measuring it on specified clinical chemistry analyzers.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- The "ground truth" for this quality control material is the assigned target concentration values for HE4 and HER2 established through repeated measurements on specific reference instruments (Siemens Centaur XP for HER2 and Roche Cobas e411 for HE4) using their corresponding reagents. This is a form of analytical reference measurement.
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The sample size for the training set
- Not Applicable. This device is a quality control material and does not use a "training set" in the context of an AI/machine learning algorithm. The "value assignment" uses multiple measurements on specific instruments to determine the target values for each level.
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How the ground truth for the training set was established
- Not Applicable. As there is no training set, this question is not relevant. However, the target values for the control material were established by measuring each analyte multiple times on the specified analyzers, and the mean value was used as the target concentration. "All supporting data is retained on file at Aalto Scientific, Ltd." (Page 6).
§ 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.