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The Procise ADL assay is a time-resolved fluorescence energy transfer immunoassay for the quantitative determination of adalimumab (ADL) levels in venous serum in patients undergoing adalimumab therapy, using the ProciseDx Analyzer.

Measurements obtained by this assay can be used to detect adalimumab as an aid in the management of patients with inflammatory bowel diseases (IBD): Crohn's disease and ulcerative colitis being treated with adalimumab. The test is intended for use in a clinical laboratory.

Device Description

Each Procise ADL assay kit includes Procise ADL reagent cartridges, buffer bulbs, and Procise ADL low and high assay controls as follows:

. Twenty pouched Procise ADL cartridges each containing a lyophilized test-specific reagent bead located in the cartridge cap comprised of test-specific conjugates (monoclonal Fab anti-ADL/TNFa complex labeled with acceptor fluorophore and TNFa protein labeled with donor fluorophore)
Twenty 1.5 mL buffer bulbs .
. Two pouched assay ADL Low controls
. Two pouched assay ADL High controls
Product Insert .
. Quick Reference Guide

The Procise ADL assay requires the ProciseDx Analyzer. The ProciseDx Analyzer is designed to detect time-resolved fluorescent signal from both the donor and FRET acceptor emission within the Procise ADL assay.

AI/ML Overview

Acceptance Criteria and Study Proving Device Meets Criteria for Procise ADL Assay

The Procise ADL assay is a quantitative, time-resolved fluorescence energy transfer immunoassay for measuring adalimumab (ADL) levels in patient serum, intended to aid in the management of inflammatory bowel disease (IBD) patients undergoing adalimumab therapy. As the provided document is a De Novo Decision Summary from the FDA, it outlines the review of the analytical performance studies conducted by the manufacturer, rather than a clinical trial with acceptance criteria for clinical efficacy. Therefore, the "acceptance criteria" here refer to the predefined performance goals the analytical studies needed to meet for FDA authorization.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric Category	Specific Metric	Acceptance Criteria (Implicit from Study Design/Results Presented)	Reported Device Performance and How it Meets Criteria
Precision/Reproducibility	Total %CV for within-laboratory precision (20-Day)	Generally, %CV below a certain threshold (e.g., typically 50 µg/mL". Device results were unimpacted by a hook effect up to 300 µg/mL.
This confirms that very high ADL levels will not cause a falsely low reading within the tested range, providing a crucial safety feature.
Assay Reportable Range	Defined measuring range	Establish a range from 1.0 to 50.0 µg/mL based on linearity and other analytical performance.	The assay reportable range was established as 1.0 to 50.0 µg/mL. This is supported by linearity, precision, and detection limit studies.
The studies confirm the device's ability to accurately quantify ADL within this range.
Traceability	Traceability to WHO IS Standard	Calibration standards traceable to the ADL WHO International Standard (NIBSC code: 17/236). Recovery study to demonstrate functional accuracy.	Calibration standards are traceable to the ADL WHO International Standard. A recovery study with the WHO IS Standard demonstrated good agreement: Slopes of 0.99-1.03 and R^2 of 1.00 for individual replicates. Individual percent biases ranged from -4% to 21%, with most at lower percentages, particularly away from the lower detection limits.
This validates the accuracy and standardization of the assay's measurements.
Sample Stability	Stability at various conditions	Support for labeling claims regarding stability at room temperature, refrigerated, frozen (-80°C), and multiple freeze-thaw cycles.	Room Temp/Refrigerated: Supported 3 days stability.
Frozen (-80°C): Supported up to 142 weeks stability.
Freeze-Thaw: Supported up to 5 freeze-thaw cycles.
These studies ensure the reliability of results given various sample handling conditions in a clinical laboratory setting.
Detection Limits	LoB, LoD, LoQ	LoB, LoD, and LoQ determined based on CLSI EP17-A2 guidelines. For LoQ, total error 0.95 or 0.98) and acceptable agreement (slope close to 1, intercept close to 0) with validated comparator methods.	N=61 samples compared to a representative comparator method. Slope = 0.91, Intercept = 1.08 µg/mL, Correlation Coefficient (r) = 0.994. Sample range tested: 2.15-42.7 µg/mL.
This demonstrates excellent agreement and correlation with existing validated methods, indicating the new assay provides comparable results.
Biosimilar Compatibility	Quantitative equivalence in measuring Amjevita®	Demonstrate quantitative equivalence in measuring the biosimilar drug Amjevita®. Linear regression coefficient of determination (R2) of 1.0.	The assay demonstrated quantitative equivalence in measuring Amjevita® across seven concentrations (2.8 to 53.3 µg/mL). Individual % Bias ranged from -1% to 10% (excluding the highest point) and the linear regression coefficient of determination (R2) was 1.0.
This confirms that the assay can accurately measure a key adalimumab biosimilar, broadening its clinical utility.

2. Sample Sizes and Data Provenance

Test Set (Analytical Studies):
- Precision (20-Day): 240 measurements per sample level (5 levels), resulting from 2 replicates/day x 2 times/day x 20 days x 3 lots/analyzers.
- Reproducibility (Multi-site): Replicates of 3, 2 times/day, for 5 days by 2 operators using 2 instruments at each of 3 external sites, for 5 serum samples. Total number of data points not explicitly summed but substantial.
- Linearity (Spiked Samples): 13 different ADL levels.
- Linearity (Native Samples): 11 serum levels.
- Analytical Specificity/Interference: Each of 21 interferents tested at 2 ADL concentrations (5 and 25 ug/mL).
- High-Dose Hook Effect: 5 ADL concentrations, tested in replicates of five using three assay lots and three buffer bulb lots.
- Procise ADL Assay Recovery Study (WHO IS Traceability): 11 dilutions of WHO IS Standard, tested in triplicates.
- Sample Stability:
  - Room Temperature & Refrigerated: 3 patients (low, mid, high range ADL), tested in duplicate at baseline, Day 3, Day 5, Day 7; used 3 lots.
  - Frozen Serum: 33 patients, tested within a day of draw, then retested in duplicate after storage at -80°C.
  - Freeze-Thaw: 5 frozen serum samples (~3-40 ug/mL ADL), tested after 1, 2, 3, and 5 freeze-thaw cycles.
- Detection Limits (LoB, LoD, LoQ):
  - LoB: 4 native serum specimens (no ADL), 5 replicates over 3 days using 2 lots (total 60 measurements per lot).
  - LoD: 4 ADL serum samples (0.1-0.5 ug/mL), 5 replicates across 3 days using 2 lots (total 60 measurements per lot).
  - LoQ: 4-5 samples, 5 replicates across 3 days using 2 lots (total 60-75 measurements per lot).
- Method Comparison: 62 deidentified serum samples.
- Biosimilar Compatibility: 7 concentrations of Amjevita® and ADL control, tested in replicates of six.
Data Provenance: The document does not specify the country of origin for the patient samples. All studies are described as analytical performance studies, which are typically retrospective in nature, using banked or collected human serum samples rather than real-time prospective clinical trials.

3. Number of Experts and Qualifications for Ground Truth

Ground Truth for Analytical Studies: Not applicable in the same way as clinical studies. For quantitative in vitro diagnostic (IVD) devices like this, the "ground truth" for analytical performance tests is typically established by:
- Known concentrations: For linearity, spike-in studies, and detection limit studies, precise dilutions of known standards (e.g., ADL WHO International Standard) are used.
- Reference methods/comparators: For method comparison studies, the "ground truth" is established by results from already validated and established comparator methods.
- Pooled samples / neat samples: For precision, stability, and interference, the "ground truth" is the established concentration of the pooled or neat human serum samples as measured by a reference method or confirmed by the manufacturer's internal processes.
Experts: No external experts (e.g., radiologists for imaging) are mentioned for establishing ground truth for these analytical performance studies. The studies are performed by laboratory personnel following established CLSI guidelines, implying the "experts" are the qualified laboratory scientists and statisticians who conduct and analyze the studies.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1 consensus) are typically used in clinical studies, especially those involving subjective interpretation of data (e.g., image reading).
For quantitative analytical performance studies of an IVD, explicit "adjudication" of results is not generally performed in the same manner. The data is quantitative, and performance is assessed statistically against predefined criteria based on CLSI guidelines. Any discrepancies would be investigated through root cause analysis rather than expert consensus on individual results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was done.
This device is a quantitative in vitro diagnostic assay for a measurand (adalimumab levels), not an AI-assisted diagnostic imaging device that involves human reader interpretation. Therefore, a MRMC study or assessment of human reader improvement with AI assistance is not applicable. The device provides a direct quantitative measurement.

6. Standalone (Algorithm Only) Performance

This is a standalone quantitative in vitro diagnostic device. Its performance is the algorithm's (assay's) performance. It does not involve human interpretation within its primary function where a human-in-the-loop scenario would be relevant for separate evaluation. The "ProciseDx Analyzer" is the instrument platform that runs the assay and displays the results.

7. Type of Ground Truth Used

The ground truth for the various analytical studies included:

Known concentrations/Spiking: For linearity, detection limits, high-dose hook effect, and biosimilar compatibility, samples were prepared with precisely known concentrations of ADL or ADL biosimilars by spiking into negative serum or by serial dilution from a concentrated stock.
Reference Standards: Specifically, the ADL WHO International Standard (NIBSC code: 17/236) served as the ultimate reference for traceability and accuracy verification.
Established Comparator Methods: For method comparison, previously validated and accepted clinical laboratory methods for measuring adalimumab served as the ground truth.
Native Patient Samples: Used for precision, stability, and interference studies, with their ADL concentrations determined by the assay itself or an established method as a baseline.

8. Sample Size for the Training Set

The document describes analytical performance studies for assay validation, not a machine learning model that requires a distinct "training set" of data.
For an IVD assay, the "training" aspect is inherent in the assay's development and optimization process (e.g., reagent formulation, instrument calibration, algorithm for calculating concentration from raw signal), which is an iterative process often using a combination of characterized biological samples, synthetic samples, and controls. The specific sample size for this development phase is not detailed in a regulatory summary focused on validation.

9. How the Ground Truth for the Training Set Was Established

Since there isn't a defined "training set" as in a machine learning context, the concept of establishing ground truth for it is not directly applicable.
The "ground truth" used during the development and optimization of such an assay would typically be established by:
- Pharmacopoeial standards and reference materials: Highly characterized ADL raw materials and formulated drug products.
- Gravimetric and volumetric preparations: Precisely prepared solutions and dilutions using analytical balances and calibrated pipettes to create samples with known ADL concentrations.
- Well-characterized biological matrices: Pooled human serum from healthy donors or patients, characterized for background interference or spiked with known amounts of ADL.
- Comparison to established research methods: During early development, comparison to gold standard research-level assays or mass spectrometry might be used to confirm initial assay performance.

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