(31 days)
The Prealbumin SPIA™ is a quantitative turbidimetric assay intended for the detection of prealbumin levels in human serum and plasma. Measurement of prealbumin levels may aid in the assessment of an individual's nutritional status.
Raichem's Prealbumin SPIA ™ is a quantitative turbidimetric assay for the detection and measurement of prealbumin in human serum and plasma. The assay has been standardized to a CAP Reference Preparation. The assay reagents consist of a polymer diluent, a polyclonal antibody to human prealbumin, calibrators, and controls. In this assay, a complex forms between the prealbumin, and anti-prealbumin antibodies causing turbidity. The change in optical density is proportional to the amount of prealbumin present. A quantitative determination of the amount of prealbumin present in a serum/plasma sample is made by comparison to a standard curve.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
The device, Prealbumin SPIA™, is a quantitative turbidimetric assay for detecting and measuring prealbumin in human serum and plasma. Its intended use is to aid in assessing an individual's nutritional status. The primary "acceptance criteria" for this 510(k) submission are related to demonstrating substantial equivalence to an existing predicate device. This is primarily shown through performance data that confirms the proposed device's analytical precision, correlation with the predicate, and suitability for its intended use.
Here's a table summarizing the performance data presented, which serves as the fulfillment of acceptance criteria for substantial equivalence:
| Acceptance Criteria Category | Specific Metric/Study | Predicate/Comparator | Performance Goal/Expectation (Implicit) | Reported Device Performance |
|---|---|---|---|---|
| Precision | Inter-assay reproducibility | (Not applicable Directly) | Low Coefficient of Variation (%CV) | Inter-assay: %CV between 4.7% and 6.7% for various samples. |
| Intra-assay reproducibility | (Not applicable Directly) | Low Coefficient of Variation (%CV) | Intra-assay: %CV between 2.5% and 5.7% for various samples. | |
| Standardization | Calibrator standardization | CAP Reference Preparation | Standardization within dynamic range (0-55 mg/dL) | Standardized within dynamic range (0-55 mg/dL) using CAP Reference Preparation. |
| Assay Sensitivity | Detection Limit | (Not explicitly defined reference) | Low detection limit for clinical relevance | 0.9 mg/dL |
| Method Comparison | Linear Correlation with Predicate Device | Incstar Antibody Reagent Set II for Prealbumin | High degree of linear correlation (e.g., r² close to 1, slope close to 1, intercept close to 0) | YPROPOSED = 1.06 XPREDICATE - 1.15 |
| "Results indicated a high degree of linear correlation." (r² not explicitly stated here, but implied as strong) | ||||
| Method Equivalency | Manual vs. Automated Method (COBAS-MIRA) Comparison | Manual method using Prealbumin SPIA™ | High degree of linear correlation (e.g., r² close to 1, slope close to 1, intercept close to 0) | VAUTOMATED = 1.10 XMANUAL + 1.07, r² = 0.959 |
| "Results indicated a high degree of linear correlation." | ||||
| Interference | Tolerable concentrations of interfering substances | (No specific limits stated, but generally minimal interference) | Minimal effect ( 200 mg/dL (significant decreases) | |
| Specimen Compatibility | Serum vs. Plasma (EDTA) | (No specific limits stated) | Accurate estimates in both human serum and EDTA-plasma | "Can provide accurate estimates of prealbumin levels in both human serum and EDTA-plasma." |
Study Details for Acceptance Criteria
2. Sample Size Used for the Test Set and Data Provenance
- Inter-assay reproducibility: 8 different serum samples, assayed 10 times over 6 different days.
- Intra-assay reproducibility: 8 serum samples, assayed 20 consecutive times in a single run.
- Method Comparison (Predicate): 134 serum specimens.
- Method Comparison (Manual vs. Automated): 30 serum samples.
- Assay Performance with Serum and Plasma: 25 matched serum and EDTA-plasma samples.
Data Provenance: The document does not explicitly state the country of origin for the samples or if they were retrospective or prospective. Given the context of a 510(k) submission in the US, it is reasonable to assume the studies were conducted in the US, likely with a mix of patient and healthy donor samples. The phrase "serum specimens from individuals being screened for prealbumin levels and apparently healthy blood donors" suggests a mix, likely from a clinical lab setting.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Not applicable in the traditional sense for this type of device. This device is an in-vitro diagnostic (IVD) for measuring a biomarker. The "ground truth" for the test set is established by the analytical measurement itself, cross-referenced against established methods or reference materials.
- For the standardization of calibrators, the College of American Pathologists (CAP) Reference Preparation for Proteins in Human Serum (Catalog Number RM002) served as the reference standard. This means an established, certified reference material sets the "ground truth" for the calibrators, not individual experts.
4. Adjudication Method for the Test Set
- Not applicable. Adjudication typically refers to expert review processes for subjective data (e.g., imaging, pathology slides). For quantitative IVD assays, the "truth" is determined by the analytical method and reference materials, not by expert consensus or review of conflicting interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC study was not done. MRMC studies are typically used for diagnostic imaging or other subjective interpretation tasks where multiple human readers interpret cases, often with and without AI assistance, to assess the impact of AI on reader performance. This device is an automated, quantitative assay, not an assistive tool for human interpretation in that context.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, this entire submission effectively describes standalone performance. The Prealbumin SPIA™ device is an automated or manual assay that directly produces quantitative results without requiring human interpretation for its primary function. The performance data (precision, sensitivity, correlation) are all measures of the algorithm/reagent system's intrinsic analytical capabilities. The "manual method" comparison is still about the assay's performance, not human interpretation.
7. The Type of Ground Truth Used
- Analytical Reference Standards and Comparative Methods.
- For calibrator standardization, the ground truth was the College of American Pathologists (CAP) Reference Preparation for Proteins in Human Serum.
- For method comparison studies, the "ground truth" was established by the predicate device (Incstar Antibody Reagent Set II for Prealbumin) or the manual method of the proposed device, to which the automated method was compared for correlation. These are accepted analytical methods rather than clinical outcomes or pathology.
- For precision and sensitivity, the ground truth is statistical derivation from multiple measurements around known concentrations or the absence of the analyte.
8. The Sample Size for the Training Set
- The document does not explicitly mention a separate "training set" as would be typical for machine learning algorithms. This device is a reagent-based turbidimetric assay, not a machine learning model that undergoes a distinct training phase with a dedicated dataset. The development and optimization of the assay would involve internal testing and validation, but this is not usually referred to as a "training set" in the context of traditional IVD development.
9. How the Ground Truth for the Training Set Was Established
- Not applicable. As noted above, there's no mention of a distinct "training set" in the machine learning sense. The ground truth for developing and optimizing the assay would have been established through a combination of using purified prealbumin, established reference methods, and internal quality control materials to ensure the assay reagents and protocols accurately measure prealbumin concentrations.
§ 866.5060 Prealbumin immunological test system.
(a)
Identification. A prealbumin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the prealbumin (a plasma protein) in serum and other body fluids. Measurement of prealbumin levels in serum may aid in the assessment of the patient's nutritional status.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.