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510(k) Data Aggregation
(660 days)
The Procise IFX assay is a time-resolved fluorescence energy transfer immunoassay for the quantitative determination of infliximab levels in venous serum in patients undergoing infliximab therapy, using the ProciseDx Analyzer.
Measurements obtained by this assay can be used to detect infliximab as an aid in the management of patients with inflammatory bowel diseases (IBD): Crohn's disease and ulcerative colitis being treated with infliximab. The test is intended for use in a clinical laboratory.
Each Procise IFX assay kit includes Procise IFX reagent cartridges, buffer bulbs, and Procise IFX low and high assay controls as follows:
- Twenty pouched Procise IFX cartridges each containing a lyophilized test-specific reagent bead contains a dry reagent bead located in the cartridge cap comprised of
The provided text describes the analytical performance characteristics of the Procise IFX assay, which is a quantitative immunoassay for measuring infliximab levels. This is an in vitro diagnostic device, and thus the acceptance criteria and supporting studies are focused on analytical performance rather than clinical performance based on human reader interpretation. Therefore sections relating to human reader studies (MRMC, expert number/qualifications, adjudication) are not applicable.
Here's a summary of the acceptance criteria and the studies that prove the device meets them:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly present a table of "acceptance criteria" alongside "reported device performance." Instead, it describes various performance studies and their results, which implicitly demonstrate that the device meets acceptable analytical standards for an in vitro diagnostic. Based on the provided data, the implicit acceptance criteria would be for the device to demonstrate robust performance across key analytical metrics.
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision | Low %CV across a range of IFX concentrations and various conditions. | 20-Day Precision: Total %CV ranged from 5.2% to 10.6% across 5 IFX concentrations (2.37-43.77 µg/mL). |
| Reproducibility (3 external sites): Total %CV ranged from 5.3% to 7.0% across 5 IFX concentrations (2.86-37.46 µg/mL). | ||
| Linearity | Samples within the measuring range demonstrate linear correlation. | Reported: Slope = 1.07, Intercept = -0.21, R² = 0.9992 for a sample range of 0.6-80 µg/mL, supporting the claimed measuring range of 1.2-50 µg/mL. |
| Analytical Specificity | No significant interference from common substances. | No significant interference (bias ≤10%) observed from 21 tested compounds at specified concentrations, including other drugs, metabolites, and endogenous substances (e.g., Adalimumab, Bilirubin, Hemolysate, Human Anti-Mouse Antibody, Rheumatoid Factors). |
| High Dose Hook Effect | No hook effect up to a certain high concentration. | Results unimpacted by a hook effect at IFX concentrations of up to 300 µg/mL. For results >50 µg/mL, the analyzer displayed ">50 µg/mL". |
| Assay Reportable Range | Clearly defined and supported by data. | 1.2 to 50.0 µg/mL (supported by linearity study). |
| Traceability | Traceable to a recognized international standard. | Calibrators traceable to IFX WHO International Standard: 1st International Standard for Infliximab (NIBSC code: 16/170). Recovery study showed good correlation (Pearson's R of 1.00) and low %Bias (mostly within ±10%) compared to the WHO IS Standard for IFX. |
| Sample Stability | Acceptable stability under various storage conditions. | Room Temperature & Refrigerated: 3 days stability (supported for 3 patients). |
| Frozen: Stable up to 142 weeks at -80°C (for 37 patients). | ||
| Freeze-Thaw: Stable up to 5 freeze-thaw cycles at -80°C (for 5 samples). | ||
| Detection Limit | Clearly defined LOB, LOD, and LOQ. | LoB: 0.08 µg/mL. |
| LoD: 0.28 µg/mL. | ||
| LoQ: 1.2 µg/mL (at 33% total error). | ||
| Method Comparison | Good correlation with existing validated methods. | Comparator 1 (N=53): Slope = 1.04, Intercept = -0.84, Correlation Coefficient (r) = 0.97. |
| Comparator 2 (N=53): Slope = 0.99, Intercept = -0.50, Correlation Coefficient (r) = 0.99. | ||
| Comparator 3 (N=77): Slope = 1.05, Intercept = 1.26, Correlation Coefficient (r) = 0.98. | ||
| Biosimilar Detection | Accurately detects biosimilar drugs. | Inflectra: % Bias ranged from -3% to 3% across 7 concentrations. |
| Renflexis: % Bias ranged from -7% to 3% across 7 concentrations. |
2. Sample sizes used for the test set and the data provenance
- Precision/Reproducibility:
- 20-Day Precision: 5 pools of native serum samples, each tested in 240 replicates (replicates of two, two times per day, for twenty days).
- Reproducibility (External Sites): 5 serum samples (3 pools of native serum, 2 QC samples). Each sample tested in 3 replicates, two times per day, for five days at 3 external sites.
- Linearity: 13 different IFX levels created from native serum samples.
- Analytical Specificity/Interference: Pooled IFX negative serum combined with native IFX serum samples at approximately 2.5, 4, and 7 µg/mL, plus each interferent at twice CLSI recommended levels.
- High Dose Hook Effect: Serum samples at 5 IFX concentrations (25, 50, 100, 200, 400 µg/mL), tested in 5 replicates.
- Traceability/Recovery Study: 11 dilutions of WHO IS Standard for IFX created using native IFX negative serum, tested in triplicates.
- Sample Stability:
- Room Temp & Refrigerated: Freshly drawn serum from 3 patients.
- Frozen: Freshly drawn serum from 37 patients.
- Freeze-Thaw: 5 frozen serum samples.
- Detection Limit:
- LoB: 4 native serum specimens (no IFX), tested in 5 replicates over 3 days (60 measurements/lot).
- LoD: 4 different IFX samples (0.1, 0.2, 0.4, 0.5 µg/mL), tested in 5 replicates across 3 days (60 measurements/lot).
- LoQ: 4 samples above LOD (0.5, 0.7, 0.9, 1.2 µg/mL), tested in 5 replicates across 3 days (60 measurements/lot).
- Method Comparison:
- 53 deidentified serum samples for comparison with Comparators 1 and 2.
- 77 additional serum samples for comparison with Comparator 3.
- Biosimilar Detection: Pooling IFX negative human serum to create 7 different levels each of Infliximab, Inflectra, and Renflexis, tested in 6 replicates.
Data Provenance: The document generally refers to "native serum samples" and "freshly drawn serum from patients." The absence of specific country of origin or explicit statements about being prospective/retrospective for all samples implies the data is likely a mix, but importantly, the studies focus on analytical performance using human serum samples. Given the context of an FDA de novo request for an in vitro diagnostic, the data is typically considered highly controlled and collected for the purpose of demonstrating analytical performance. The use of "deidentified serum samples" for method comparison suggests retrospective use or collection for research purposes where patient identity is removed.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not applicable. This device is an in vitro diagnostic for quantitative measurement of a biomarker (infliximab) and does not involve human interpretation of images or clinical cases that would require expert consensus for ground truth. The ground truth for analytical studies is typically established by reference methods, known concentrations, or certified reference materials (like the WHO International Standard).
4. Adjudication method for the test set
Not applicable. As noted above, this device measures a quantitative biomarker and does not involve subjective human interpretation or diagnostic decisions that would require adjudication.
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
Not applicable. This is an in vitro diagnostic device, not an AI-assisted diagnostic tool requiring human reader involvement.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, this is effectively a standalone device (algorithm only without human-in-the-loop performance in terms of diagnostic interpretation). The "ProciseDx Analyzer" automatically measures the FRET signal and determines the IFX concentration based on the ratio of emissions. Its performance is entirely characterized by its analytical capabilities, as detailed in the performance characteristics section.
7. The type of ground truth used
The ground truth for the analytical studies was primarily established using:
- Reference Standards: For traceability, the Procise IFX assay calibration standards are traceable to the IFX WHO International Standard (NIBSC code: 16/170). Known concentrations derived from this standard served as ground truth for recovery and accuracy.
- Validated Comparator Methods: For method comparison studies, three existing validated comparator methods were used to establish the comparative ground truth.
- Known Concentrations: For precision, linearity, interference, hook effect, and biosimilar detection studies, samples were prepared with known or targeted IFX concentrations, allowing for direct comparison of the device's measurements against these pre-defined values.
- Native Serum Samples: For various studies, native human serum samples were used to represent real-world clinical samples.
8. The sample size for the training set
The document does not explicitly delineate a "training set" in the context of machine learning or AI algorithm development. For an in vitro diagnostic device like the Procise IFX assay, the "training" for the assay's performance characteristics (e.g., calibration curves, reagent optimization) is inherent in the assay development and validation processes, which typically involve extensive testing with various concentrations and sample types, often using reference materials and clinical samples. This is represented by the multiple studies and samples outlined under the "Performance Characteristics" section.
9. How the ground truth for the training set was established
Similar to point 8, the concept of a "training set" with distinct ground truth establishment for an AI algorithm is not directly applicable. However, the development of the assay's fundamental operating parameters and calibration (i.e., the "training" the device undergoes to produce accurate results) relies on rigorous analytical studies using:
- WHO International Standard: As mentioned, the traceability section indicates the use of the IFX WHO International Standard, which would be crucial for establishing the quantitative relationship between the assay's signal and actual infliximab concentration.
- Defined Prepared Samples: The linearity, precision, and other analytical studies use samples prepared with known concentrations of infliximab, which serve as the ground truth for characterizing the assay's performance across its measuring range.
- Existing Validated Methods: Comparison to established methods helps ensure that the new assay's measurements are consistent with accepted quantitative approaches.
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