(90 days)
Immunoassay for the in vitro quantitative determination of procainamide in human serum and plasma.
The CEDIA® Procainamide Assay is based on the bacterial enzyme ßgalactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically. In the assay, procainamide in the sample competes with analyte conjugated to one inactive fragment of ß-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed.
This document describes the Boehringer Mannheim CEDIA® Procainamide Assay, a homogeneous enzyme immunoassay for the quantitative determination of procainamide in human serum and plasma. The information provided outlines the device's technical characteristics and performance compared to a predicate device, the Abbott TDx® Procainamide Assay.
Here's an analysis of the provided information regarding acceptance criteria and the supporting study:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in this summary. Instead, the performance characteristics of the CEDIA® Procainamide Assay are presented and implicitly compared to those of the predicate device (Abbott TDx® Procainamide Assay) to demonstrate substantial equivalence. The "acceptance criteria" can be inferred to be performance comparable to or better than the predicate device.
| Feature | Acceptance Criteria (Inferred from Predicate Device Performance) | CEDIA® Procainamide Performance |
|---|---|---|
| Precision (Level 1 %CV) | Total %CV: ~5.4% (TDx Low) | Total %CV: 3.1% |
| Precision (Level 2 %CV) | Total %CV: ~4.2% (TDx Mid) | Total %CV: 3.0% |
| Precision (Level 3 %CV) | Total %CV: ~4.6% (TDx High) | Total %CV: 2.8% |
| Lower Detection Limit | ≤ 0.1 µg/dL | 0.4 µg/dL |
| Linearity Range | 0.0 - 20.0 µg/dL | 0.4 - 20 µg/dL |
| Method Comparison (r-value vs. predicate) | r ≥ 0.990 (TDx vs. EIA) | r = 0.9914 (CEDIA vs. TDx) |
| Bilirubin Interference | No interference at 15 mg/dL | No interference at 66 mg/dL |
| Hemoglobin Interference | No interference at 1000 mg/dL | No interference at 1000 mg/dL |
| Lipemia Interference | No interference at 1200 mg/dL | No interference at 1000 mg/dL |
| Protein Interference | No interference at 9.5 mg/dL | No interference at 6.5 g/dL Albumin, 10 g/dL IgG |
| N-Acetyl-procainamide Cross-reactivity | 1.0 % | 1.0 % |
| Desethyl-procainamide Cross-reactivity | 15 % | 16.3 % |
Summary of Performance vs. Inferred Criteria:
- Precision: The CEDIA® assay demonstrates better or comparable precision (lower %CV) across all levels compared to the predicate device.
- Lower Detection Limit: The CEDIA® assay's lower detection limit (0.4 µg/dL) is higher than the predicate's (0.1 µg/dL), indicating potentially slightly less sensitivity at very low concentrations.
- Linearity: The linearity range is similar, though the CEDIA's lower bound is 0.4 µg/dL compared to 0.0 µg/dL for the predicate.
- Method Comparison: A strong correlation (r=0.9914) is shown between the CEDIA® assay and the predicate TDx assay, indicating good agreement.
- Interfering Substances: The CEDIA® assay shows improved tolerance to bilirubin interference and comparable tolerance to hemoglobin and lipemia, with different protein interference concentrations reported.
- Specificity/Cross-reactivity: The cross-reactivity for N-Acetyl-procainamide is identical, and for Desethyl-procainamide, it is very similar. Additional cross-reactivity for Procaine HCl is reported for CEDIA®.
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Test Set:
- N: 120 for each of 3 levels (Total N = 360 individual runs for CEDIA® assay precision testing).
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). This is a common omission in 510(k) summaries for in-vitro diagnostics where the studies are typically conducted internally by the manufacturer using controlled samples. It is implied to be prospective testing conducted for the submission.
- Method Comparison Test Set:
- N: 122 samples for the comparison between CEDIA® Procainamide and Abbott TDx Procainamide.
- Data Provenance: Not explicitly stated. Likely prospective testing given the nature of method comparison studies.
- Interfering Substances, Specificity/Cross-reactivity, Lower Detection Limit, Linearity: No specific N values are given for these tests, but they involve a series of experiments.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is generally not applicable for an in-vitro diagnostic (IVD) assay like the CEDIA® Procainamide Assay.
- For IVDs that measure an analyte concentration, the "ground truth" is typically the reference method (e.g., mass spectrometry, or in this case, the predicate device if it's considered a reliable standard) or the known concentration within a manufactured control sample.
- There are no "experts" establishing ground truth in the sense of image interpretation or clinical diagnosis. The "truth" is the measured chemical concentration.
4. Adjudication Method for the Test Set
This is not applicable for this type of IVD performance study. Adjudication methods (like 2+1, 3+1) are used in clinical trials or studies where human interpretation or consensus is required to establish a clinical endpoint or diagnosis, not for analytical performance testing of an enzyme immunoassay measuring circulating drug levels.
5. 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 is relevant for imaging devices or AI-assisted diagnostic tools where human interpretation is a key component. This document describes an automated laboratory assay for measuring drug levels, which does not involve human readers interpreting results in the same way an imaging study would.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, this entire submission describes the standalone performance of the CEDIA® Procainamide Assay. This is an automated diagnostic test that provides a quantitative result based on its internal enzymatic reactions and spectrophotometric measurements. There isn't a "human-in-the-loop" in the sense of interpreting raw output, but rather a human operating the instrument and using the numeric result for clinical decision-making.
7. The Type of Ground Truth Used
The ground truth used for these analytical studies is:
- Known concentrations: For precision, linearity, lower detection limit, interfering substances, and cross-reactivity, the "ground truth" is typically established by preparing samples with known, precise concentrations of the analyte (procainamide) and potential interferents. These concentrations are usually verified by a primary reference method if available.
- Predicate Device/Reference Method: For method comparison, the "ground truth" for patient samples is essentially the result obtained from the predicate device (Abbott TDx® Procainamide Assay), which is considered the established method for comparison in this context. While not explicitly stated, it's implied that the Abbott TDx® assay served as the comparative standard. The TDx assay itself would have a foundation in comparison to a more definitive "gold standard" method when it was first cleared.
8. The Sample Size for the Training Set
The document does not mention a training set. This is because the CEDIA® Procainamide Assay is a biochemical assay, not a machine learning or AI model that requires a dedicated training set. The assay's performance is based on its chemical and enzymatic design, not on patterns learned from data.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the context of this biochemical assay, this question is not applicable.
§ 862.3320 Digoxin test system.
(a)
Identification. A digoxin test system is a device intended to measure digoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.(b)
Classification. Class II.