(20 days)
Assayed control material for in vitro diagnostic use to monitor the precision and accuracy of immunochemistry test procedures for the ADVIA Centaur® andACS:180® Systems.
The Ligand Plus 1, 2, 3 Controls are three separate levels of quality control material prepared from human serum with non-serum constituents added. The analytes currently in the control material are: Alphafetoprotein, Carbamazepine, CEA, Digoxin, Cortisol, Gentamicin, Estradiol, Phenobarbital, Ferritin, Phenytoin, Folic Acid, Theophylline, FSH, Tobramycin, HCG, Valproic Acid, IgE, Vancomycin, LH, Progesterone, Prolactin, PSA, T3, T3-free, T4, T4-free, Testosterone, Thyroid Uptake, TSH, TSH-3, Vitamin B12. The intention of this submission is to add the following three constituents to the existing control: Intact PTH (iPTH, or intact parathyroid hormone), Insulin, c-Peptide.
Here's a breakdown of the acceptance criteria and study information based on the provided text, focusing on the absence of detailed performance data as this is a Class I device and the submission primarily concerns adding new analytes to an existing control.
1. Table of Acceptance Criteria and Reported Device Performance
The provided 510(k) summary for the Ligand Plus 1, 2, 3 Controls does not include a table of specific numerical acceptance criteria or reported device performance metrics (e.g., accuracy, precision values, sensitivity, specificity).
This is primarily because:
- The device is a Class I quality control material, which typically requires demonstrating that it functions as intended (i.e., provides stable and accurate control values) rather than providing diagnostic results itself.
- The submission is for the addition of three new analytes (iPTH, Insulin, and c-Peptide) to an already cleared predicate device. The primary concern is that these new analytes integrate without compromising the control's known function.
- The "Substantial Equivalence" section emphasizes the identity of intended use, storage, handling, stability, source material, and instructions for use with the predicate device.
Instead of specific performance numbers, the "acceptance criteria" here would be demonstrating that the new analytes behave as expected for a quality control material and do not negatively impact the overall functionality or existing cleared analytes of the control. This would involve validation studies (which are generally not detailed in a Class I 510(k) summary in this manner) showing the control provides stable, reproducible results when run on the specified instruments.
For a quality control product, "performance" is typically demonstrated by:
- Target Value Assignment: Showing that the control can be assigned appropriate target values for the added analytes.
- Stability: Demonstrating the stability of the added analytes over the product's shelf-life.
- Lot-to-Lot Consistency: Ensuring consistency between different manufacturing lots.
- Matrix Effects: Confirming that the control matrix is suitable for the specified assays.
The document implicitly states that these aspects were successfully addressed to achieve substantial equivalence.
2. Sample Size Used for the Test Set and Data Provenance
The 510(k) summary does not specify the sample size used for any test set or the data provenance (e.g., country of origin, retrospective/prospective). This level of detail is typically not required or provided in Class I 510(k) summaries for quality control materials for added analytes to an existing control. Demonstrating "substantial equivalence" for a control material often relies on internal validation studies and comparison to existing methods/materials rather than extensive clinical trial data.
3. Number of Experts Used to Establish Ground Truth and Qualifications
This information is not applicable and not provided.
- The device is a quality control material, not a diagnostic device that interprets patient samples. Therefore, "ground truth" as established by experts in clinical interpretation (e.g., radiologists, pathologists) is not relevant to its performance.
- Ground truth for a control material involves the accurate assignment of analyte concentrations (target values), which is determined by the manufacturer through rigorous analytical methods and reference measurements, not by expert consensus on clinical findings.
4. Adjudication Method for the Test Set
This information is not applicable and not provided for the same reasons as #3. Adjudication by experts is relevant for diagnostic devices interpreting complex clinical data, not for the analytical performance of a quality control material.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A MRMC comparative effectiveness study was not done. This type of study focuses on the impact of a diagnostic tool on human reader performance (e.g., radiologists, pathologists) in interpreting medical images or complex data. Since the device is a quality control material (for in vitro diagnostic use to monitor precision and accuracy of immunochemistry tests), human interpretation of results is not directly assessed in the way an MRMC study would measure. Its role is to ensure the analyzers are performing correctly.
6. Standalone Performance Study
While not explicitly called a "standalone performance study" in the context of diagnostic algorithms, the underlying studies to support the addition of the new analytes would involve standalone analytical performance evaluations of the control material itself. These studies would assess:
- Assigned values and expected ranges for iPTH, Insulin, and c-Peptide.
- Reproducibility (precision) of these analytes when measured on the ADVIA Centaur® and ACS:180® Systems.
- Stability of these analytes in the control matrix over time and under various storage conditions.
- Homogeneity within and between vials.
The positive outcome of these internal analytical studies would have formed the basis for the submission, allowing the FDA to deem the device "substantially equivalent."
7. Type of Ground Truth Used
The "ground truth" for a quality control material like this involves analytically derived target values and acceptable ranges for the analytes. These would be established by:
- Reference measurement procedures: Highly accurate and precise laboratory methods (often traceable to international reference materials).
- Interlaboratory studies: Testing the control material across multiple qualified laboratories to establish consensus values.
- Manufacturer's internal validation: Extensive testing using the intended platform (ADVIA Centaur® and ACS:180® Systems) to determine the expected values and performance characteristics.
This is not "expert consensus" in the clinical sense, nor is it based on pathology or outcomes data. It is purely analytical.
8. Sample Size for the Training Set
This information is not applicable and not provided. "Training set" refers to data used to train machine learning algorithms. This device is a biochemical control material, not an AI or machine learning-based diagnostic device.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable and not provided for the same reasons as #8.
§ 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.