(29 days)
ALP IFCC Gen.2 is an in vitro test intended for the quantitative determination of the catalytic activity of alkaline phosphatase in human serum and plasma on COBAS INTEGRA systems. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
The Roche ALP IFCC Gen.2 assay provides quantitative measurement of the catalytic activity of alkaline phosphatase in human serum and plasma in accordance with a standardized method.. The reagents are packaged in a cassette with two bottles labeled with their instrument positioning, R1 (position B) and SR (position C).
In the presence of magnesium and zinc ions, p-nitrophenyl phosphate is cleaved by phosphatases into phosphate and p-nitrophenol. The p-nitrophenol released is directly proportional to the catalytic ALP activity. It is determined by measuring the increase in absorbance.
Here's an analysis of the provided text regarding the acceptance criteria and study information:
This document is a 510(k) summary for a diagnostic assay, not an AI/ML device. Therefore, many of the typical questions for AI/ML studies (like MRMC studies, reader performance, training set details, etc.) are not applicable here. The acceptance criteria and performance are for an in vitro diagnostic (IVD) reagent and its analytical performance.
1. Table of Acceptance Criteria and Reported Device Performance
The document describes modifications to an existing device (ALP IFCC Gen.2). The acceptance criteria are implicit in the "Pass/Fail criteria" for the verification and validation tests performed. The "reported device performance" refers to the characteristics of the modified device and the confirmation that it met these criteria.
| Performance Characteristic | Acceptance Criterion (Implicit) | Reported Device Performance (Modified ALP IFCC Gen.2) |
|---|---|---|
| Measuring Range | 3.0 - 1200 U/L (consistent with predicate/intended use) | 3.0 - 1200 U/L |
| Lower Detection Limit (LDL) | 3.0 U/L (consistent with predicate/intended use) | 3.0 U/L |
| Precision | "See predicate method sheet" (implies performance is comparable) | "Same" as predicate (meaning performance met the established precision specifications for the predicate) |
| Method Comparison | "See predicate method sheet" (implies performance is comparable) | "Same" as predicate (meaning the method comparison with established methods yielded comparable results to the predicate, likely within established statistical agreement limits) |
| Interference: Hemolysis | No significant interference up to 0.16 mmol/L (2.5 g/L) hemoglobin | No significant interference up to hemoglobin level of 0.16 mmol/L (2.5 g/L). |
| Interference: Icterus | No significant interference up to specified I index levels | No significant interference up to an I index of 42 for conjugated bilirubin and 60 for unconjugated bilirubin. (This is an improvement/addition to the predicate which simply stated "No significant interference.") |
| Interference: Lipemia | No significant interference up to specified L index levels | No significant interference up to an L index of 2000. (This is an improvement/addition to the predicate which simply stated "No significant interference.") |
| Traceability/Standardization | Standardized against the IFCC (2011) reference procedure | Standardized against the IFCC (2011) procedure. (This is the primary change and was successfully implemented.) |
| Recovery in Controls | Met pre-determined Pass/Fail criteria for accuracy | Passed all tests based on pre-determined Pass/Fail criteria (specific values not provided, but implies recovery was within acceptable limits for various control levels across the measuring range). |
| Linearity | Met pre-determined Pass/Fail criteria for linearity across range | Passed all tests based on pre-determined Pass/Fail criteria (specific values not provided, but implies the assay demonstrated linear response across its measuring range within acceptable deviations). |
Summary of the Study:
The document describes a Special 510(k) Premarket Notification for modifications to an existing in vitro diagnostic device, ALP IFCC Gen.2. The core purpose was to change the traceability standard of the assay and add specific interference claims. The "study" refers to the verification, validation, and testing activities conducted to confirm that these modifications did not adversely affect the device's performance and that the new claims were supported.
Breakdown of Information Request:
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Table of acceptance criteria and reported device performance: See table above.
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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):
- Sample Size: Not explicitly stated. The document mentions "verification, validation and testing activities" including "recovery in controls, linearity, method comparison, within run precision and interference characteristics." For these types of analytical studies, samples typically include:
- Controls: Multiple replicates, often 2-3 levels, run over several days/runs for precision and recovery.
- Linearity samples: A series of diluted or spiked samples across the measuring range.
- Method Comparison samples: A set of patient samples (often 40-100+) covering the assay range, compared against a reference method or the predicate device.
- Interference samples: Patient samples or spiked samples tested with various concentrations of interferents (hemoglobin, bilirubin, lipids).
- Data Provenance: Not explicitly stated, but standard practice for Roche Diagnostics (a global company with manufacturing in Germany and operations in the US) would be internal lab testing, likely at their R&D facilities in Germany or the US. It would be prospective testing of the modified device.
- Sample Size: Not explicitly stated. The document mentions "verification, validation and testing activities" including "recovery in controls, linearity, method comparison, within run precision and interference characteristics." For these types of analytical studies, samples typically include:
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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):
- This question is not applicable in the context of an IVD reagent analytical performance study. "Ground truth" for an IVD assay's performance would be established by:
- Highly accurate reference measurement procedures (e.g., the IFCC (2011) reference method cited for traceability).
- Certified reference materials.
- Comparison against a legally marketed predicate device or a clinical laboratory's established, validated method.
- No "experts" in the sense of clinical reviewers are typically used to establish ground truth for analytical performance, but rather highly skilled laboratory scientists and metrologists ensure the accuracy of the reference methods and measurements.
- This question is not applicable in the context of an IVD reagent analytical performance study. "Ground truth" for an IVD assay's performance would be established by:
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- This question is not applicable. Adjudication methods like "2+1" or "3+1" are characteristic of clinical studies involving human interpretation (e.g., image reading), where disagreements among reviewers need resolution. This document describes analytical performance testing of a reagent where results are quantitative and objective.
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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:
- This is not applicable. An MRMC study assesses the performance of human readers, often with and without AI assistance, on a set of cases. This document is about the analytical performance of an in vitro diagnostic reagent, not an AI/ML device or human reader performance.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- This is not applicable. The device is an in vitro diagnostic reagent executed on an automated instrument (COBAS INTEGRA systems). Its performance is inherently "standalone" in functionality (it performs the assay automatically), but it's not an algorithm in the AI/ML sense that would have an "algorithm only" performance study. Its performance is the instrument's performance running the reagent.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For this type of analytical IVD study, the "ground truth" for method comparison and traceability would be:
- Reference Measurement Procedures: Specifically, the modified IFCC (2011) reference method for ALP activity.
- Certified Reference Materials/Calibrators: These provide established, highly accurate values.
- Comparison to Predicate Device: The performance of the modified device was compared to the legally marketed predicate, which itself would have been validated against established clinical laboratory methods or reference methods.
- For this type of analytical IVD study, the "ground truth" for method comparison and traceability would be:
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The sample size for the training set:
- This is not applicable. This is an IVD reagent, not an AI/ML algorithm that requires a "training set." The reagent's formulation and associated analytical procedures are developed through biochemical and analytical chemistry principles, not machine learning training.
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How the ground truth for the training set was established:
- This is not applicable for the same reason as point 8.
§ 862.1050 Alkaline phosphatase or isoenzymes test system.
(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.