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The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of Methadone Metabolite in human urine. The cutoff for both the qualitative and semi-quantitative modes of the assay are 100 ng/mL and 300 ng/mL for methadone metabolite. The assay is designed for prescription use on automated clinical chemistry analyzers.

The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas or liquid chromatography/mass spectrometry (GCMS or (2) permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical result. A more specific alternative analytical chemistry method must be used in order to obtain a confirmed analytical result. Gas or liguid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.

The LZI Methadone Metabolite (EDDP) (100 and 300) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay at the cutoff values of 100 ng/mL and 300 ng/mL.

Device Description

The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between EDDP in the sample and EDDP labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the EDDP concentration in the sample is measured in terms of enzyme activity. In the absence of EDDP in the sample, EDDP-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free EDDP is present in the sample, antibody would bind to free EDDP; the unbound EDDP-labeled G6PDH then exhibits its maximal enzyme activity. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.

The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.

The Ri solution contains mouse monoclonal anti-methadone metabolite antibody, glucose-6phosphate (G6P) nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with methadone metabolite in buffer with sodium azide (0.09 %) as a preservative.

The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay calibrators and controls designated for use at the 100 ng/mL cutoff contain 0, 50, 75, 100, 125, 250, 500 ng/mL of methadone metabolite (EDDP) in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.

The LZI Methadone Metabolite (EDDP) Enzyme Immunoassay calibrators and controls designated for use at the 300 ng/mL cutoff contain 0, 150, 225, 300, 375, 600, and 1000 ng/mL of methadone metabolite (EDDP) in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.

AI/ML Overview

The provided document is a 510(k) premarket notification for the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay and Calibrators. It focuses on demonstrating substantial equivalence to a predicate device, rather than establishing acceptance criteria and proving conformance to them in the same way a de novo or PMA submission might.

Therefore, the acceptance criteria are largely implied by the comparison to the predicate device and the analytical performance data presented. The study aims to show that the new device performs comparably to the predicate and provides accurate results for methadone metabolite detection.

Here's an attempt to extract the requested information based on the provided text, with notable limitations due to the nature of the document:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Characteristic	Acceptance Criteria (Implied)	Reported Device Performance
Precision (100 ng/mL Cutoff)	Consistency in qualitative results (Negative/Positive) at various concentrations, particularly near the cutoff, demonstrating minimal variation within and between runs. For concentrations <75 ng/mL, results should be consistently negative. For concentrations >125 ng/mL, results should be consistently positive. At the 100 ng/mL cutoff, a mix of positive and negative results is expected due to inherent variability, but overall agreement with expected ranges should be demonstrated.	Semi-Quantitative Results:- 0, 25, 50, 75 ng/mL: 100% Negative (Within Run N=22, Total N=88)- 100 ng/mL (Cutoff): Within Run: 11 Neg/11 Pos (50%); Total: 40 Pos/48 Neg (45.5% Pos)- 125, 150, 175, 200 ng/mL: 100% Positive (Within Run N=22, Total N=88)Qualitative Results:- 0, 25, 50, 75 ng/mL: 100% Negative (Within Run N=22, Total N=88)- 100 ng/mL (Cutoff): Within Run: 13 Neg/9 Pos (40.9% Pos); Total: 34 Pos/54 Neg (38.6% Pos)- 125, 150, 175, 200 ng/mL: 100% Positive (Within Run N=22, Total N=88)
Precision (300 ng/mL Cutoff)	Consistency in qualitative results (Negative/Positive) at various concentrations, particularly near the cutoff, demonstrating minimal variation within and between runs. For concentrations <225 ng/mL, results should be consistently negative. For concentrations >375 ng/mL, results should be consistently positive. At the 300 ng/mL cutoff, a mix of positive and negative results is expected due to inherent variability, but overall agreement with expected ranges should be demonstrated.	Semi-Quantitative Results:- 0, 75, 150, 225 ng/mL: 100% Negative (Within Run N=22, Total N=88)- 300 ng/mL (Cutoff): Within Run: 6 Neg/16 Pos (72.7% Pos); Total: 52 Pos/36 Neg (59.1% Pos)- 375, 450, 525, 600 ng/mL: 100% Positive (Within Run N=22, Total N=88)Qualitative Results:- 0, 75, 150, 225 ng/mL: 100% Negative (Within Run N=22, Total N=88)- 300 ng/mL (Cutoff): Within Run: 7 Neg/15 Pos (68.2% Pos); Total: 55 Pos/33 Neg (62.5% Pos)- 375, 450, 525, 600 ng/mL: 100% Positive (Within Run N=22, Total N=88)
Method Comparison - Clinical Samples (100 ng/mL Cutoff)	High concordance with LC/MS results, especially for samples clearly positive or negative relative to the cutoff. Discrepancies should be understood and ideally minimal, particularly for samples significantly above/below the cutoff. The device should demonstrate appropriate sensitivity and specificity compared to a confirmatory method.	Qualitative/Semi-Quantitative Accuracy Study (N=87):- Agreement for 23 Negative, 11 <50% of cutoff, 9 Near Cutoff Neg, 40 High Pos.- 2 discordant samples: Sample #45 (LC/MS 103.1 ng/mL, EIA Negative); Sample #46 (LC/MS 126.0 ng/mL, EIA Negative). These were "Near Cutoff Pos" by LC/MS but negative by EIA. This indicates the EIA may be less sensitive for results very close to the cutoff, which is acceptable for a screening assay requiring confirmation.
Method Comparison - Clinical Samples (300 ng/mL Cutoff)	High concordance with LC/MS results, especially for samples clearly positive or negative relative to the cutoff. Discrepancies should be understood and ideally minimal, particularly for samples significantly above/below the cutoff. The device should demonstrate appropriate sensitivity and specificity compared to a confirmatory method.	Qualitative/Semi-Quantitative Accuracy Study (N=84):- Agreement for 21 Negative, 15 <50% of cutoff, 6 Near Cutoff Neg, 38 High Pos.- 4 discordant samples: These were "Near Cutoff Pos" by LC/MS but positive by EIA (no specific concentrations provided, but implies the EIA correctly identified them as positive, while LC/MS categorized them differently near the cutoff based on the table structure). The table indicates 4 samples were "Near Cutoff Pos" by LC/MS and "Positive" by EIA. No 'Negative' results for these 'Near Cutoff Pos' samples are shown as in the 100ng/mL cutoff.
Cross-reactivity	Minimal or no cross-reactivity with structurally related compounds that are not the target analyte, ensuring specificity of the assay.	100 ng/mL Cutoff:- EDDP: 100% Cross Reactivity- EMDP, Methadone, LAAM HCl, (±)-α-Methadol, (-)-Isomethadone HCl, (-)-α-Noracetylmethadol (Nor-LAAM) HCl: <0.1% or <0.2% Cross Reactivity (i.e., consistently Negative at high spiked concentrations).300 ng/mL Cutoff:- EDDP: 100% Cross Reactivity- EMDP, Methadone, LAAM HCl, (±)-α-Methadol, (-)-Isomethadone HCl, (-)-α-Noracetylmethadol (Nor-LAAM) HCl: <0.1% Cross Reactivity (i.e., consistently Negative at high spiked concentrations).
Endogenous Compound Interference & Specific Gravity	No significant undesired interference from common endogenous compounds or variations in specific gravity.	"No significant undesired cross-reactants or endogenous substance interference was observed."
Intended Use	The device should be reliably used for qualitative and semi-quantitative determination of Methadone Metabolite in human urine at specified cutoffs (100 ng/mL and 300 ng/mL) on automated clinical chemistry analyzers for prescription use, providing preliminary analytical results requiring confirmatory methods.	The performance data supports the claims for qualitative and semi-quantitative determination at both 100 ng/mL and 300 ng/mL cutoffs, indicating it functions as intended for preliminary screening.

2. Sample Size Used for the Test Set and Data Provenance

Precision Studies:
- For each concentration level tested (e.g., 0, 25, 50, 75, 100, 125, 150, 175, 200 ng/mL for 100 ng/mL cutoff, and similarly for 300 ng/mL cutoff), there were N=22 samples for "Within Run" analysis and N=88 samples for "Total Precision" analysis. This suggests 4 runs (88/22).
- Total number of unique samples for precision is not explicitly stated as distinct samples across all concentrations, but it's at least 9 concentrations x 22 samples for within-run and 9 concentrations x 88 for total precision for each cutoff. These are likely replicates of specific concentrations rather than 88 unique patient samples.
- Data Provenance: Not specified (e.g., country of origin). Likely laboratory-prepared spiked samples for precision. Retrospective or Prospective is not stated but typically spiked samples are prepared for the study.
Method Comparison - Clinical Samples:
- 100 ng/mL Cutoff: N=87 clinical unaltered samples.
- 300 ng/mL Cutoff: N=84 clinical unaltered samples.
- Data Provenance: "clinical unaltered samples." Not specified (e.g., country of origin, retrospective or prospective), but implies real patient samples.
Cross-reactivity: The sample sizes are implied by the "Spiked []" concentrations for each cross-reactant. Each cross-reactant was tested at a specific concentration. This is generally a set of controlled laboratory-prepared samples.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

Ground Truth Method: The primary ground truth for the clinical sample method comparison and for validating the calibrators/controls is Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS).
Number/Qualifications of Experts: The document does not specify the number of experts or their qualifications involved in establishing the GC/MS or LC/MS ground truth. This is a common characteristic of device submissions where a recognized "gold standard" analytical method (like GC/MS or LC/MS for drug testing) is used, and the expertise is assumed to be inherent in the execution of that method by a qualified laboratory.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method involving multiple human readers or a formal adjudication process beyond using GC/MS/LC/MS as the confirmatory method. The presented data primarily compares the EIA results directly to LC/MS results. For the two discordant samples at the 100 ng/mL cutoff, their LC/MS concentrations are noted, but no further "adjudication" is detailed in the text beyond acknowledging the discrepancy.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done as described in the document. This type of study typically assesses human reader performance with and without AI assistance for tasks like image interpretation. This submission is for an in vitro diagnostic (IVD) immunoassay, not an AI-powered diagnostic imaging device.

6. Standalone Performance Study (Algorithm Only)

Yes, this entire submission is essentially a standalone performance study of the "algorithm" (the LZI Methadone Metabolite (EDDP) Enzyme Immunoassay). The performance characteristics (precision, method comparison, cross-reactivity) demonstrate the device's analytical performance without human intervention in the interpretation of the raw assay signal, as it's designed for automated clinical chemistry analyzers. The "EIA Result" is the output of the device itself.

7. Type of Ground Truth Used

The primary ground truth used is confirmatory analytical chemistry methods, specifically Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). These are considered highly accurate and specific "gold standards" for drug quantification.

8. Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of an AI/machine learning model. This is an IVD device, where performance is established through analytical validation studies (precision, accuracy, interference, cross-reactivity) using predefined reagents and methods. The device's "algorithm" is the enzymatic reaction and spectrophotometric measurement, which is inherently deterministic, not a learned model in the AI sense.
The calibrators are used for the calibration of the assay (0, 50, 100, 250, 500 ng/mL for 100 ng/mL cutoff; 0, 150, 300, 600, 1000 ng/mL for 300 ng/mL cutoff), which is analogous to "setting up" the device for accurate measurement.

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

As there is no "training set" in the AI/ML context, this question is not directly applicable. For the calibrators, their concentrations are precisely defined (e.g., 100 ng/mL or 300 ng/mL of methadone metabolite (EDDP)). These are manufactured with known concentrations in a human urine matrix. The "ground truth" for calibrators is therefore their known, manufactured concentration.

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