Search Results

The LZI Fentanyl III Enzyme Immunoassay is intended for the qualitative determination of fentanyl in human urine at the cutoff value of 1 ng/mL when calibrated against fentanyl. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.

The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used in order to obtain a confirmed analytical result. 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 Fentanyl III Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between the drug in the sample and the drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. The drug-labeled G6PDH conjugate is traceable to a commercially available fentanyl standard and referred to as fentanyl-labeled G6PDH conjugate. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of a drug in the sample, fentanyl-labeled G6PDH conjugate is bound to the antibody, and the enzyme activity is inhibited. On the other hand, when the free drug is present in the sample, the antibody would bind to the free drug; the unbound fentanyl-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 Fentanyl III Enzyme Immunoassay is a kit comprised of two reagents, R1 and R2, which are bottled separately but sold together within the kit.

The R1 solution contains mouse monoclonal anti-fentanyl antibody, glucose-6-phosphate (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 fentanyl in buffer with sodium azide (0.09%) as a preservative.

The provided FDA 510(k) Clearance Letter for the LZI Fentanyl III Enzyme Immunoassay details the device's acceptance criteria (in terms of performance characteristics) and the study results that demonstrate the device meets these criteria.

Here's a breakdown of the requested information:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the satisfactory performance demonstrated in the various studies, aiming to prove substantial equivalence to the predicate device. The performance characteristics sections show the device meets the expected qualitative and quantitative accuracy, precision, and specificity.

• Negative by LC/MS analysis: 35 negatives, 0 positives by EIA.
• ** 50% above cutoff) by LC/MS:** 0 negatives, 61 positives by EIA.

Overall, 35/35 true negatives, 83/83 true positives (excluding near-cutoff positives and positives above cutoff). The remaining 32 discrepant samples (20 + 12) were positive by EIA but negative by LC/MS for fentanyl, indicating cross-reactivity with norfentanyl as a contributing factor. |
| Precision | Consistent and reliable qualitative results (positive/negative) across multiple runs and days, especially around the cutoff concentration. | Precision: 1 ng/mL Cutoff (N=88 total replicates over 22 days):

• 0 ng/mL, 0.25 ng/mL, 0.5 ng/mL, 0.75 ng/mL: 88/88 Negative (100% agreement).
• 1 ng/mL (Cutoff): 4 Neg / 84 Pos (95.5% Positive, 4.5% Negative - demonstrating near-cutoff variability, which is expected for qualitative assays at the cutoff).
• 1.25 ng/mL, 1.5 ng/mL, 1.75 ng/mL, 2 ng/mL: 88/88 Positive (100% agreement). |
  | Cross-Reactivity (Specificity) | Minimal or no false positives from structurally unrelated compounds. Acceptable cross-reactivity with fentanyl metabolites and structurally related compounds as defined by the assay's intended specificity. | Fentanyl and Metabolites: Fentanyl (100%), Norfentanyl (40%).
  Structurally Related Compounds: Varying levels of cross-reactivity (e.g., Acetyl fentanyl 25%, Acryl fentanyl 100%, Thiofentanyl 200%). Many substances showed "ND" (Not Detected) at high concentrations (e.g., 100,000 ng/mL).
  Structurally Unrelated Pharmacological Compounds: No interference (all Neg/Neg/Pos results for 0 ng/mL Fentanyl, -50% Cutoff, +50% Cutoff respectively) at 100,000 ng/mL for almost all listed compounds, except Dextromethorphan, which showed interference at 20,000 ng/mL (Neg/Pos/Pos) but was acceptable at 15,000 ng/mL (Neg/Neg/Pos). This demonstrates good specificity against common drugs. |
  | Interference | Test performance (positive/negative results) should not be significantly affected by common endogenous substances or preservatives found in urine, or by varying specific gravity and pH within physiological ranges. | Endogenous and Preservative Compound Interference: No interference observed for most compounds (e.g., Acetone, Ascorbic acid, Bilirubin, Glucose, Hemoglobin) at high concentrations (e.g., 100,000 mg/dL), showing Neg/Neg/Pos results for 0 ng/mL, -50% Cutoff, +50% Cutoff respectively. Boric acid showed interference at 1,000 mg/dL (Neg/Neg/Neg), indicating a potential issue if present at high concentrations. This is a known interference for certain urine assays.
  Specific Gravity Interference: No interference observed across the range of 1.000 to 1.030 (all Neg/Neg/Pos).
  pH Interference: No major interference observed between pH 3 to pH 11 (all Neg/Neg/Pos). |

2. Sample Size and Data Provenance

• Test Set Sample Size:
  • Precision Study: 88 replicates for each concentration level (0 ng/mL to 2 ng/mL fentanyl).
  • Method Comparison (Clinical Samples): 150 unaltered clinical samples.
  • Cross-Reactivity: Duplicates for each compound and concentration tested.
  • Interference (Endogenous/Preservative): Duplicates for each compound and concentration tested.
  • Specific Gravity/pH Interference: Duplicates for each specific gravity/pH level and fentanyl concentration.
• Data Provenance:
  • The clinical samples for the Method Comparison study were obtained by LZI and "through collaboration with various clinical laboratories across the United States and Canada." This indicates a prospective and/or retrospective collection of real-world clinical samples from diverse geographical regions. The nature (retrospective/prospective) of the collection for these specific 150 samples isn't explicitly stated but "clinical samples" usually implies samples collected from patients.

3. Number of Experts and Qualifications for Ground Truth

• The document does not specify the number of experts used to establish ground truth.
• Qualifications of Experts: Not explicitly stated. However, for LC/MS confirmation, it implicitly relies on the expertise of the laboratory personnel performing and interpreting the LC/MS (Liquid Chromatography-Mass Spectrometry) analysis, which is a gold standard for chemical identification and quantification. These would typically be trained analytical chemists or lab technicians with experience in mass spectrometry.

4. Adjudication Method for the Test Set

• The document does not describe an adjudication method for the test set in the typical sense of multiple human readers or reviewers resolving discrepancies.
• For the Method Comparison study, the "ground truth" was established independently by LC/MS. Discrepancies between the EIA result and the LC/MS result were reported and attributed to norfentanyl cross-reactivity. This is a comparison against a reference method, not a subjective adjudication by experts.

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

• No, an MRMC comparative effectiveness study was not done. This type of study is more common for diagnostic imaging AI algorithms where human interpretation is a primary component and AI aims to augment or replace it. This document describes an in vitro diagnostic (IVD) assay, an enzyme immunoassay, which is an automated lab test. Its performance is evaluated against a reference standard (LC/MS), not against human reader performance.

6. Standalone Performance

• Yes, standalone performance was done. The entire submission details the performance of the LZI Fentanyl III Enzyme Immunoassay as a standalone device. The qualitative accuracy, precision, cross-reactivity, and interference studies all evaluate the algorithm/device's performance independently in generating a preliminary analytical result from a urine sample. It does not involve human-in-the-loop performance; rather, it provides a result that a clinician then interprets in conjunction with other clinical data.

7. Type of Ground Truth Used

• The primary type of ground truth used for the quantitative confirmation of fentanyl concentration in the clinical samples (Method Comparison study) was LC/MS (Liquid Chromatography-Mass Spectrometry) analysis. This is considered a highly specific and sensitive reference method for drug quantification.

8. Sample Size for the Training Set

• The document does not explicitly state the sample size for the training set. The described studies are verification and validation activities for a modified assay (Special 510(k) for an existing predicate device, LZI Fentanyl II). For IVD assays, "training" often refers to the internal development and optimization of the assay performed by the manufacturer, which precedes the formal V&V studies presented for regulatory submission. The reported studies are the test set performance.

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

• Since the training set size is not explicitly stated, the method for establishing ground truth for it is also not explicitly described. However, it is highly probable that internal development and optimization of the assay would have utilized similar rigorous analytical methods, likely LC/MS or other established analytical techniques, to calibrate and refine the assay's performance against known concentrations of fentanyl and its metabolites. This would be part of the manufacturer's design control and development process.

Ask a specific question about this device

The LZI Oxycodone III Enzyme Immunoassay is intended for the quantitative determination of oxycodone in human urine at the cutoff values of 100 ng/mL when calibrated against oxycodone. The assay is designed for prescription use with a number of 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 GC/MS or (2) permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatograpy and mass spectrometry) must be used in order to obtain a confirmed analytical result. 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 Oxycodone III Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. The drug-labeled G6PDH conjugate is traceable to a commercially available oxycodone standard and referred to as oxycodone-labeled G6PDH conjugate. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, oxycodone-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound oxycodone-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 Oxycodone III Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2, which are bottled separately but sold together within the kit. The LZI Oxycodone III Enzyme Immunoassay is traceable to a commercially available oxycodone standard.

The Ri solution contains mouse monoclonal anti-oxycodone antibody, glucose-6-phosphate (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 oxycodone in buffer with sodium azide (0.09 %) as a preservative.

The document provided describes the LZI Oxycodone III Enzyme Immunoassay, a device for detecting oxycodone in human urine. This is a chemical assay, not an AI/ML-based device. Therefore, many of the requested criteria related to AI/ML or imaging studies (like number of experts, adjudication methods, MRMC studies, training/test set sample sizes, and ground truth establishment for AI/ML models) are not applicable.

However, I can extract and present the acceptance criteria for a chemical assay and the study that proves the device meets those criteria based on the provided text.

Device Name: LZI Oxycodone III Enzyme Immunoassay

Device Type: Homogeneous enzyme immunoassay (chemical assay)

Intended Use: Qualitative and semi-quantitative determination of oxycodone in human urine at cutoff values of 100 ng/mL and 300 ng/mL. The assay provides only a preliminary analytical result, requiring a more specific alternative chemical method (e.g., GC/MS or LC/MS) for confirmation.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for a chemical assay are typically defined by performance characteristics such as precision, analytical recovery, accuracy (method comparison with a gold standard), cross-reactivity, and interference studies.

Cutoff 1: 100 ng/mL

• 0-75 ng/mL: 100% Negative
• 125-200 ng/mL: 100% Positive
• 100 ng/mL: 5 Neg / 17 Pos (Semi-quantitative), 9 Neg / 13 Pos (Qualitative)
  Total Precision (N=88 determinations):
• 0-75 ng/mL: 100% Negative
• 125-200 ng/mL: 100% Positive
• 100 ng/mL: 26 Neg / 62 Pos (Semi-quantitative), 33 Neg / 55 Pos (Qualitative) |
  | Analytical Recovery | Determined concentration should be within a specified percentage of the target concentration across the assay range. | Performed across a range of 0-300 ng/mL by serial dilution of a 300 ng/mL spiked sample. Average % Recovery ranged from 90.3% to 110.0% for concentrations 30-300 ng/mL. The 0 ng/mL sample showed 0.7 ng/mL determined average. |
  | Method Comparison (Accuracy) | High agreement with a confirmatory method (LC/MS) across different concentration ranges (negative, near cutoff negative/positive, high positive). | Clinical Samples (N=82), compared to LC/MS:
  Semi-Quantitative Results:
• Positive agreement: 90.2% (2 discordants in "Near Cutoff Negative" range, 4 discordants in "Near Cutoff Positive" range)
• Negative agreement: 95.1% (4 discordants in "Near Cutoff Positive" range)
  Qualitative Accuracy Study (same data):
• Positive agreement: 90.2%
• Negative agreement: 95.1%
  Discordant samples often contained oxymorphone, indicating potential cross-reactivity or combined effect of oxycodone and its metabolite. |
  | Cross-reactivity | Low or no cross-reactivity with structurally unrelated compounds and expected cross-reactivity with major metabolites and structurally related compounds. | Oxycodone & Major Metabolites:
• Oxycodone, Oxymorphone: 100.00%
• Noroxycodone: 0.40%
• Noroxymorphone: 0.17%
  Structurally Related Compounds: Hydrocodone (0.40%), Hydromorphone (0.40%), Oxymorphone-3β-D-Glucuronide (43.48%). Most others (e.g., Codeine, Morphine, Buprenorphine, Naloxone) showed ND (Not Detected) at 100,000 ng/mL. The study confirmed expected positive and negative results at ±25% of cutoff for various other pharmacological compounds. |
  | Interference (Endogenous & Preservative) | No significant interference observed with common endogenous substances or preservatives at relevant concentrations. | No significant interference observed for most compounds (e.g., Acetone, Ascorbic Acid, Bilirubin, Creatinine, Ethanol, Glucose, Hemoglobin, Urea, etc.) at tested concentrations (up to 6000 mg/dL).
  Boric Acid: Showed interference at 1000 mg/dL at ±25% of cutoff (Negative result for both 75 ng/mL and 125 ng/mL oxycodone samples), but not at ±50% of cutoff. This indicates a potential suppression of the signal by high concentrations of boric acid. |
  | Specific Gravity Interference | No deviations from expected results over a range of specific gravity values. | No deviations from expected positive or negative results across specific gravity 1.000 to 1.030 when spiked at ±25% of cutoff (75 ng/mL and 125 ng/mL oxycodone). |
  | pH Interference | No deviations from expected results over a physiological pH range. | No deviations from expected results across pH levels from 3 to 11 when spiked at ±25% of cutoff (75 ng/mL and 125 ng/mL oxycodone). |

Cutoff 2: 300 ng/mL

• 0-225 ng/mL: 100% Negative
• 375-600 ng/mL: 100% Positive
• 300 ng/mL: 6 Neg / 16 Pos (Semi-quantitative), 10 Neg / 12 Pos (Qualitative)
  Total Precision (N=88 determinations):
• 0-225 ng/mL: 100% Negative
• 375-600 ng/mL: 100% Positive
• 300 ng/mL: 27 Neg / 61 Pos (Semi-quantitative), 40 Neg / 48 Pos (Qualitative) |
  | Analytical Recovery | Determined concentration should be within a specified percentage of the target concentration across the assay range. | Performed across a range of 0-800 ng/mL by serial dilution of an 800 ng/mL spiked sample. Average % Recovery ranged from 104.5% to 111.5% for concentrations 80-800 ng/mL. The 0 ng/mL sample showed 0.3 ng/mL determined average. |
  | Method Comparison (Accuracy) | High agreement with a confirmatory method (LC/MS) across different concentration ranges. | Clinical Samples (N=90), compared to LC/MS:
  Semi-Quantitative Results:
• Positive agreement: 97.8% (2 discordants in "Near Cutoff Negative" range, 1 discordant in "Near Cutoff Positive" range)
• Negative agreement: 95.6% (1 discordant in "Near Cutoff Positive" range)
  Qualitative Accuracy Study (same data):
• Positive agreement: 95.6%
• Negative agreement: 95.6%
  Discordant samples often involved significant oxymorphone concentrations relative to oxycodone. |
  | Cross-reactivity | Low or no cross-reactivity with structurally unrelated compounds and expected cross-reactivity with major metabolites and structurally related compounds. | Oxycodone & Major Metabolites:
• Oxycodone, Oxymorphone: 100.00%
• Noroxycodone: 0.40%
• Noroxymorphone: ND (Not Detected) at 100,000 ng/mL.
  Structurally Related Compounds: Hydrocodone (0.40%), Hydromorphone (0.40%), Oxymorphone-3β-D-Glucuronide (42.86%). Most others (e.g., Codeine, Morphine, Buprenorphine, Naloxone) showed ND at 100,000 ng/mL. The study confirmed expected positive and negative results at ±25% of cutoff for various other pharmacological compounds. |
  | Interference (Endogenous & Preservative) | No significant interference observed with common endogenous substances or preservatives at relevant concentrations. | No significant interference observed for most compounds (e.g., Acetone, Ascorbic Acid, Bilirubin, Creatinine, Ethanol, Glucose, Hemoglobin, Urea, etc.) at tested concentrations (up to 6000 mg/dL).
  Boric Acid: Showed interference at 1000 mg/dL at ±25% of cutoff (Negative result for both 225 ng/mL and 375 ng/mL oxycodone samples), but for 300 ng/mL cutoff, it showed Negative at 150 ng/mL and Positive at 450 ng/mL, indicating it might behave differently at higher concentrations or different % of cutoff. |
  | Specific Gravity Interference | No deviations from expected results over a range of specific gravity values. | No deviations from expected positive or negative results across specific gravity 1.000 to 1.030 when spiked at ±25% of cutoff (225 ng/mL and 375 ng/mL oxycodone). |
  | pH Interference | No deviations from expected results over a physiological pH range. | No deviations from expected results across pH levels from 3 to 11 when spiked at ±25% of cutoff (225 ng/mL and 375 ng/mL oxycodone). |

Study Details:

As this is a chemical immunoassay and not an AI/ML device, certain questions are not relevant. However, I will answer the applicable points:

2. Sample sizes used for the test set and data provenance:

• Test set (Clinical Samples for Method Comparison):
  • 100 ng/mL Cutoff: 82 unaltered clinical samples
  • 300 ng/mL Cutoff: 90 unaltered clinical samples
• Precision Studies: Spiked pooled negative urine samples, tested in replicates, resulting in 88 total determinations per concentration level across 22 days.
• Analytical Recovery Studies: Serially diluted spiked pooled negative urine, each sample run in 10 replicates.
• Cross-reactivity and Interference Studies: Spiked pooled negative human urine, tested in duplicates.
• Data Provenance: Not explicitly stated, but clinical samples typically imply real-world specimens. The location (country of origin) and retrospective/prospective nature are not specified in this summary.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

• Not applicable as the ground truth for this chemical assay was established by a well-defined analytical standard: Liquid Chromatography–Mass Spectrometry (LC/MS), which is considered a gold standard for drug quantitative analysis in urine. This is a laboratory-based, objective ground truth, not reliant on human expert interpretation of images or other subjective data.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

• Not applicable. Ground truth for chemical assays is based on quantitative analytical methods (LC/MS), not on expert consensus or 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 a standalone chemical immunoassay, not an AI-assisted diagnostic tool that involves human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

• Yes, the performance characteristics described (Precision, Analytical Recovery, Method Comparison, Cross-reactivity, Interference, Specific Gravity, pH Interference) represent the standalone performance of the LZI Oxycodone III Enzyme Immunoassay. The device generates a quantitative or semi-quantitative result directly from the sample. Humans are involved in operating the automated clinical chemistry analyzer and interpreting the results, but a "human-in-the-loop" performance study as typically understood for AI models (e.g., radiologists interpreting images with or without AI guidance) is not relevant here.

7. The type of ground truth used:

• Confirmed Analytical Result: Gas Chromatography/Mass Spectrometry (GC/MS) or Liquid Chromatography/Mass Spectrometry (LC/MS). For the method comparison studies, LC/MS was explicitly stated as the confirmation method for oxycodone and oxymorphone concentrations.

8. The sample size for the training set:

• Not applicable. This is a laboratory-developed and validated chemical assay, not an AI/ML model that requires a "training set" in the machine learning sense. The assay's parameters (e.g., reagent concentrations, antibody specificity) are developed and optimized through traditional biochemical and analytical chemistry methods, rather than by training on a dataset.

9. How the ground truth for the training set was established:

• Not applicable for the same reason as #8. The "ground truth" for developing such a chemical assay lies in analytical chemistry principles and the use of well-characterized reference standards and controls to determine its performance characteristics.

Ask a specific question about this device

The LZI Fentanyl II Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.

The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used in order to obtain a confirmed analytical result. 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 Fentanyl II Enzyme Immunoassay is a homogeneous enzyme immunoassay with readyto-use liguid reagents. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. The drug-labeled G6PDH conjugate is traceable to a commercially available fentanyl standard and referred to as fentanyl-labeled G6PDH conjugate. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, fentanyl-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound fentanyllabeled 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 Fentanyl II Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit. The LZI Fentanyl II Enzyme Immunoassay is traceable to a commercially available fentanyl standard.

The R1 solution contains mouse monoclonal anti-fentanyl antibody, glucose-6-phosphate (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 fentanyl in buffer with sodium azide (0.09 %) as a preservative.

The LZI Fentanyl II Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at a cutoff value of 5 ng/mL. The device provides a preliminary analytical result, and a more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used for a confirmed analytical result.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance:

Ask a specific question about this device

The LZI Tramadol Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of tramadol in human urine at the cutoff value of 100 ng/mL when calibrated against tramadol. The assay is designed for prescription use with a number of 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 (GC/MS or LC/MS) or (2) permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used in order to obtain a confirmed analytical result. 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 Tramadol Enzyme Immunoassay is a homogeneous enzyme immunoassay with readyto-use liquid reagents. The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. The drug-labeled G6PDH conjugate is traceable to a commercially available tramadol standard and referred to as tramadol-labeled G6PDH conjugate. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, tramadol-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound tramadol-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 Tramadol Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit. The LZI Tramadol Enzyme Immunoassay is traceable to a commercially available tramadol standard.

The Ri solution contains mouse monoclonal anti-tramadol antibody, glucose-6-phosphate (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 tramadol in buffer with sodium azide (0.09 %) as a preservative.

The provided text describes the performance characteristics of the LZI Tramadol Enzyme Immunoassay. Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly list "acceptance criteria" for precision, recovery, or method comparison in a consolidated table with specific numerical targets like "sensitivity > X%" or "specificity > Y%". Instead, it presents the raw performance data and concludes that the results are acceptable or show no significant interference. However, using the precision study's implicit goal (correct qualitative classification for samples ± 25% of cutoff) and the method comparison's agreement, and the recovery study's target, we can construct the following:

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

• Precision Test Set: Not clinical samples. Tramadol samples were prepared by spiking a tramadol standard into a pool of negative human urine.
  • For qualitative and semi-quantitative modes: 8 concentrations (0, 25, 50, 75, 100, 125, 150, 175, 200 ng/mL). Each concentration was tested in duplicate, two runs a day for 22 days, totaling 88 replicates per concentration.
• Analytical Recovery: Not clinical samples. A drug-free urine pool spiked with tramadol at 400 ng/mL was serially diluted. Each dilution was run in 10 replicates.
• Method Comparison - Clinical Samples: Eighty-six (86) unaltered clinical samples.
  • Provenance: Samples were collected by Lin-Zhi International, Inc. (LZI) and the University of California at San Francisco (UCSF, San Francisco). This indicates a retrospective collection of clinical samples from a US-based origin.
• Cross-reactivity, Endogenous/Preservative Interference, Specific Gravity, pH Interference: Not clinical samples. Prepared by spiking substances into pooled negative human urine. All samples were tested in duplicates (except for Analytical Recovery, which was 10 replicates).

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

N/A. This device is an in-vitro diagnostic assay for tramadol in urine. The ground truth for the clinical samples was established using a "more specific alternative chemical method," specifically LC/MS (Liquid Chromatography/Mass Spectrometry), which is a gold standard analytical technique for drug quantification, not human expert interpretation. For the spiked samples (precision, recovery, interference studies), the ground truth was the known concentration of the spiked substance, not expert consensus.

4. Adjudication Method for the Test Set

N/A. The ground truth for clinical samples was established by LC/MS analysis, which is an objective chemical measurement. There was no human expert adjudication of results, as there would be in an image analysis or diagnostic interpretation study.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This device is an automated enzyme immunoassay, not an AI-assisted diagnostic tool that involves human reader interpretation. Therefore, there is no "human readers improve with AI vs without AI assistance" effect size to report. The study focuses on the analytical performance of the immunoassay itself in comparison to a confirmatory method (LC/MS).

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, the studies presented are standalone (algorithm only) performance evaluations of the LZI Tramadol Enzyme Immunoassay. The assay is automated on a clinical chemistry analyzer, and its results are compared directly to known concentrations or LC/MS results without human interpretative input as part of its primary performance.

7. The Type of Ground Truth Used

• For Clinical Samples (Method Comparison): LC/MS (Liquid Chromatography/Mass Spectrometry) was used as the confirmatory gold standard for tramadol concentrations.
• For Spiked Samples (Precision, Analytical Recovery, Cross-reactivity, Interference Studies): The ground truth was the known concentration of tramadol or interfering substance spiked into negative human urine.

8. The Sample Size for the Training Set

N/A. This is an immunoassay, not a machine learning model. It does not have a "training set" in the context of AI/ML. The assay's performance is based on its chemical and enzymatic reactions, calibrated using known standards.

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

N/A. As mentioned above, there is no "training set" for this immunoassay device. The assay uses calibrators (0, 50, 100, 225, and 400 ng/mL tramadol) to establish its calibration curve, which determines the relationship between enzyme activity and tramadol concentration. These calibrators represent known, established concentrations.

Ask a specific question about this device

The LZI Cotinine II Enzyme Immunoassay is intended for the quantitative determination of cotinine in human urine at the cutoff value of 200 ng/mL when calibrated against cotinine. The assay is intended as an aid in the detection of cotinine after use or exposure to tobacco products. The assay is designed for prescription use with a number of 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 (GC/MS or LC/MS) or (2) permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used in order to obtain a confirmed analytical result. 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 Cotinine II Enzyme Immunoassay is a homogeneous enzyme immunoassay with readyto-use liguid reagents. The assay is based on competition between drug in the sample and drug 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 drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, cotinine-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound cotinine-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 Cotinine II Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.

The R1 solution contains mouse monoclonal anti-cotinine antibody, glucose-6-phosphate (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 cotinine in buffer with sodium azide (0.09 %) as a preservative.

The provided text describes the LZI Cotinine II Enzyme Immunoassay, its intended use, and performance characteristics, but it does not describe a study that directly establishes acceptance criteria and directly proves the device meets specific acceptance criteria in a structured manner you requested.

The document is a 510(k) Summary of Safety and Effectiveness, which typically outlines the device's characteristics and demonstrates substantial equivalence to a predicate device. It includes performance data such as precision, linearity, and method comparison (accuracy) with clinical samples, which implicitly serve to show the device is safe and effective for its stated intended use. However, explicit acceptance criteria values that the device must meet are not directly listed in a table format with corresponding proof of meeting them.

I will extract the closest information available to address your request, making inferences where necessary based on the context of common performance expectations for such devices.

Here's a breakdown of the information as requested, largely derived from the "Method Comparison - Clinical Samples" and "Precision" sections.

Acceptance Criteria and Device Performance for LZI Cotinine II Enzyme Immunoassay

Note: The document does not explicitly state "acceptance criteria" in a definitive table format with corresponding proof. Instead, it presents performance study results that are implicitly considered acceptable for demonstrating substantial equivalence. The "Reported Device Performance" below is directly from the study results. The "Acceptance Criteria" are inferred based on the observed performance and typical expectations for diagnostic assays.

1. Table of Acceptance Criteria and Reported Device Performance

• 1 sample (128.6 ng/mL LC/MS) was positive by EIA but was between 50% below cutoff and cutoff concentration (100-199.9 ng/mL). The report states it was "discrepant" but the EIA result (positive) aligns with the stated LC/MS value being within the range where a positive result starts to become more likely if it's "near cutoff positive". However, interpreting that specific discrepancy is complex without a clear cut-off definition of "positive" for LC/MS in the table.
• 1 sample (204.2 ng/mL LC/MS) was negative by EIA but was between cutoff and 50% above cutoff concentration (200-299.9 ng/mL). The report states it was "discrepant". | The accuracy study uses LC/MS as the gold standard. The reported percentages reflect agreement for positive and negative results with respect to the 200 ng/mL cut-off. The discrepancies highlight inherent variability near the cutoff. |
  | Accuracy (Qualitative) | High overall agreement with LC/MS, similar to semi-quantitative.| Overall Agreement: ~96.4% for positive, ~98.7% for negative.
  Discrepant Samples:
• 1 sample (128.6 ng/mL LC/MS) was positive by EIA (146.6 mAU) with a qualitative cutoff rate of 126.4 mAU. This sample was LC/MS positive but between 100-199.9 ng/mL, the EIA result was positive.
• 1 sample (204.2 ng/mL LC/MS) was negative by EIA (93.8 mAU) with a qualitative cutoff rate of 126.4 mAU. This sample was LC/MS positive (204.2 ng/mL) but the EIA result was negative. | Similar to semi-quantitative accuracy, with concordance defined by the qualitative response based on mAU compared to a cutoff rate. |
  | Precision (Qualitative) | At 200 ng/mL cutoff, some variability is expected. For concentrations significantly above or below the cutoff, 100% agreement with expected result (positive/negative) is expected. | At 200 ng/mL:
• Within Run (N=22): 10 Neg/12 Pos
• Total Precision (N=88): 51 Neg/37 Pos
  At 250-400 ng/mL: 100% Positive
  At 0-150 ng/mL: 100% Negative | This indicates that at the exact cutoff concentration (200 ng/mL), there is expected variability in classification. This is typical for assays and is why results near the cutoff require careful interpretation and often confirmatory testing. |
  | Precision (Semi-Quantitative)| Same as qualitative. At 200 ng/mL cutoff, some variability is expected. For concentrations significantly above or below the cutoff, 100% agreement with expected result (positive/negative) is expected. | At 200 ng/mL:
• Within Run (N=22): 14 Neg/8 Pos
• Total Precision (N=88): 55 Neg/33 Pos
  At 250-400 ng/mL: 100% Positive
  At 0-150 ng/mL: 100% Negative | The semi-quantitative precision results also show variability at the 200 ng/mL cutoff, with 100% agreement for samples sufficiently above or below the cutoff. This confirms the device's ability to consistently classify samples away from the decision point. |
  | Linearity | Percent recovery between 85% and 115% of expected values across the assay's linear range. | Range 100 ng/mL to 1000 ng/mL: Recovery ranging from 97.9% to 110.8%.
  At 20 ng/mL: 167.5% recovery.
  At 0 ng/mL: N/A (reported 19.3 ng/mL determined). | The device demonstrated good linearity within the critical range for its intended use (100-1000 ng/mL). The higher recovery at 20 ng/mL suggests reduced accuracy at very low concentrations, which is generally not a concern given the 200 ng/mL cutoff. |
  | Cross-reactivity | Minimal or no significant cross-reactivity with common substances, particularly structurally unrelated compounds, at physiologically relevant concentrations or concentrations higher than expected. | Cotinine-related compounds: Some cross-reactivity with compounds like (-) Norcotinine (20.00%) and (R, S)-Norcotinine (23.53%).
  Structurally Unrelated Pharmacological Compounds: "ND" (Not Detected) at high concentrations (e.g., 100,000 ng/mL) for most tested drugs. Negative results for 0 ng/mL cotinine spiked with these compounds, and correct positive/negative results for cotinine controls. | The device largely demonstrates specificity against a wide panel of common drugs and related substances, indicating minimal interference for its intended purpose. Some expected cross-reactivity with specific cotinine metabolites is noted. |
  | Endogenous Interference | No significant interference from common endogenous substances at relevant concentrations. | No significant undesired cross-reactants or endogenous substance interference was observed except for Boric Acid (1000 ng/mL) and Citric Acid (pH 3) (800 ng/mL) which showed interference at ±25% of cutoff and also at ±50% of cutoff. | Most endogenous substances showed no interference. Boric acid and citric acid showed interference, which is important for laboratories to be aware of when testing samples that might contain these substances. |
  | Specific Gravity Interference | No interference observed across the tested range. | No interference was observed in samples ranging from 1.005 to 1.028 specific gravity when spiked with cotinine at control concentrations. | This indicates the device is robust to variations in urine specific gravity, which is a common factor in urine drug testing. |
  | pH Interference | No major interference observed across the tested pH range. | No major interference between pH 3 to pH 11. | This demonstrates the device's robustness across a wide physiological pH range for urine, an important aspect for clinical utility. |

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

• Accuracy (Method Comparison - Clinical Samples):

  • Sample Size: 104 unaltered clinical samples.
  • Data Provenance: Samples were collected by Lin-Zhi International, Inc. (LZI). The country of origin is not specified, but LZI is based in Santa Clara, CA, USA. The samples are indicated to be "clinical samples," implying they were prospectively collected from human subjects for diagnostic purposes. They are referred to as "unaltered," suggesting they were tested as received without intentional modification. The study is retrospective in the sense that these samples were then tested against a new assay.

• Precision:

  • Sample Size: For each cotinine concentration, 22 determinations were made within a run, and a total of 88 determinations were made across multiple runs (2 runs/day for 22 days).
  • Data Provenance: Samples were prepared by spiking a cotinine standard into a "pool of negative human urine." This indicates a controlled laboratory setting (likely in-house at LZI) rather than clinical samples, and thus not tied to a specific country of origin from patients.

• Linearity, Cross-reactivity, Endogenous Interference, Specific Gravity, pH Interference: These studies used spiked samples prepared in a laboratory setting (e.g., "drug free-urine pool," "pool of negative human urine"). The sample sizes for each condition are detailed in the tables (e.g., "10 replicates" for linearity, "replicates" for others).

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

• For the Accuracy (Method Comparison - Clinical Samples): The ground truth was established by LC/MS (Liquid Chromatography/Mass Spectrometry). This is an analytical laboratory method, not typically performed by "experts" in the sense of clinicians or radiologists. The result from the LC/MS machine is the ground truth. Therefore, the concept of "number of experts" and their "qualifications" is not applicable here as the ground truth is an objective chemical measurement.

4. Adjudication Method for the Test Set

• For the accuracy study, the "ground truth" was established by LC/MS, which is a definitive analytical method. Therefore, no human adjudication method (like 2+1, 3+1 consensus) was used or required for determining the confirmed cotinine concentration. The comparison was directly between the LZI Cotinine II Enzyme Immunoassay results and the LC/MS results.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

• No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typical for imaging devices where human readers interpret images, sometimes with and without AI assistance, to assess AI's impact on human performance. The LZI Cotinine II Enzyme Immunoassay is an in-vitro diagnostic (IVD) device (a laboratory test), not an imaging device that would involve human readers for interpretation in this manner.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

• Yes, the performance studies described are essentially standalone evaluations of the LZI Cotinine II Enzyme Immunoassay. The accuracy, precision, linearity, and interference studies assess the analytical performance of the device itself (the "algorithm" in a broad sense, referring to the assay's methodology and reagents) against established reference methods or known concentrations, without requiring human intervention for interpretation beyond operating the automated clinical analyzer and analyzing the data. The results (e.g., ng/mL concentrations or positive/negative classifications) are generated directly by the assay on the automated analyzer.

7. The Type of Ground Truth Used

• Primary Ground Truth for Clinical Accuracy: LC/MS (Liquid Chromatography/Mass Spectrometry) for cotinine concentrations. This is a highly specific and sensitive analytical technique, often considered the gold standard for drug confirmation testing.
• Ground Truth for Other Studies (Precision, Linearity, Cross-reactivity, etc.): Known concentrations of cotinine or other substances (spiked samples) in negative human urine pools.

8. The Sample Size for the Training Set

• The document describes performance studies for device validation. It does not provide information about a "training set" in the context of an AI/machine learning model. This device is an enzyme immunoassay, a chemical assay, not an AI-based diagnostic algorithm that typically undergoes a separate training phase with a large dataset. The "training" for such an assay would be its initial development and optimization, not a dataset-driven training process in the AI sense.

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

• As explained in point 8, the concept of a "training set" for an AI/machine learning model is not applicable to this enzyme immunoassay device. Therefore, how its ground truth was established is not relevant here. The development of the assay's chemical reagents and methodology would have involved internal validation and optimization, but not a "training set" in the context of AI.

Ask a specific question about this device

The LZI Methadone II Enzyme Immunoassay is an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of methadone in human urine. The cutoff for both the qualitative and semi-quantitative modes of the assay is 300 ng/mL for methadone. 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 LC/MS) 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 liquid 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 II Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between methadone in the sample and methadone 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 methadone concentration in the sample is measured in terms of enzyme activity. In the absence of methadone in the sample, methadone-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free methadone is present in the sample, antibody would bind to free methadone; the unbound methadone-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 II 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 antibody, glucose-6-phosphate (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 in buffer with sodium azide (0.09 %) as a preservative.

The LZI Methadone II Enzyme Immunoassay is an in-vitro diagnostic test for qualitative and semi-quantitative determination of methadone in human urine, with a cutoff of 300 ng/mL. The device's performance was evaluated through various studies demonstrating its precision, linearity, accuracy against LC/MS, cross-reactivity with other substances, and interference from endogenous compounds and pH levels.

Here is a summary of the acceptance criteria and reported device performance from the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

• 0 ng/mL, 75 ng/mL, 150 ng/mL, 225 ng/mL: 22 Negative
• 300 ng/mL: 17 Neg / 5 Pos
• 375 ng/mL, 450 ng/mL, 525 ng/mL, 600 ng/mL: 22 Positive
  Total Precision (N=88):
• 0 ng/mL, 75 ng/mL, 150 ng/mL, 225 ng/mL: 88 Negative
• 300 ng/mL: 59 Neg / 29 Pos
• 375 ng/mL, 450 ng/mL, 525 ng/mL, 600 ng/mL: 88 Positive |
  | Semi-Quantitative Precision | Consistent positive/negative results for samples 25% away from cutoff. | Within Run (N=22):
• 0 ng/mL, 75 ng/mL, 150 ng/mL, 225 ng/mL: 22 Negative
• 300 ng/mL: 18 Neg / 4 Pos
• 375 ng/mL, 450 ng/mL, 525 ng/mL, 600 ng/mL: 22 Positive
  Total Precision (N=88):
• 0 ng/mL, 75 ng/mL, 150 ng/mL, 225 ng/mL: 88 Negative
• 300 ng/mL: 66 Neg / 22 Pos
• 375 ng/mL, 450 ng/mL, 525 ng/mL, 600 ng/mL: 88 Positive |
  | Linearity | Recovery values between 85% - 115% of expected values. | Samples from 100 ng/mL to 1000 ng/mL showed recovery ranging from 93.7% to 104.9%. |
  | Semi-Quantitative Accuracy (vs. LC/MS) | High percentage agreement with LC/MS results. | % Agreement: 97.8% (Positive), 97.9% (Negative) |
  | Qualitative Accuracy (vs. LC/MS) | High percentage agreement with LC/MS results. | % Agreement: 97.8% (Positive), 97.9% (Negative) |
  | Cross-reactivity (Structurally Related) | Low cross-reactivity for other methadone-related compounds, and no interference with unrelated compounds. | Methadone: 100.00%
  EDDP, EMDP:

Ask a specific question about this device

The LZI Fentanyl Enzyme Immunoassay is intended for the qualitative determination of norfentanyl in human urine at the cutoff value of 5 ng/mL when calibrated against norfentanyl. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.

The assay provides only a preliminary analytical result. A more specific alternative chemical method (e.g., gas or liquid chromatography and mass spectrometry) must be used in order to obtain a confirmed analytical result.

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 Fentanyl Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is based on competition between drug in the sample and drug 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 drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, norfentanyl-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug; the unbound norfentanyl-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 Fentanyl Enzyme Immunoassay is a kit comprised of two reagents, an R1 and R2 which are bottled separately but sold together within the kit.

The R1 solution contains mouse monoclonal anti-fentanyl antibody, glucose-6-phosphate (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 fentanyl in buffer with sodium azide (0.09 %) as a preservative.

The LZI Fentanyl Enzyme Immunoassay calibrators and controls are designated for use at the 5 ng/mL cutoff contain 0, 2.5, 3.75, 5, 6.25, 10, and 20 ng/mL of norfentanyl in human urine with sodium azide (0.09 %) as a preservative. These five calibrators and two controls are sold as individual bottles.

Here's an analysis of the acceptance criteria and study findings for the LZI Fentanyl Enzyme Immunoassay, based on the provided document:

This document is a 510(k) summary for a diagnostic device, which typically focuses on demonstrating substantial equivalence to a predicate device rather than comprehensive clinical effectiveness. Therefore, some of the requested information (like multi-reader multi-case studies, effect size of AI, or detailed training set information for an AI algorithm) is not applicable or present in this type of submission. The device described is a traditional enzyme immunoassay, not an AI-based system.

1. Acceptance Criteria and Reported Device Performance

The document describes performance characteristics typically assessed for an immunoassay. The primary acceptance criteria are implied by the precision and method comparison studies. For qualitative drug tests, the key is the accuracy of positive and negative determinations around the cutoff.

Note on Acceptance Criteria: For 510(k) submissions, the acceptance criteria are often benchmarked against the predicate device's performance or established standards for that device type. Explicit numerical acceptance criteria are not always stated directly in the summary document but are implicit in the study design and the finding of "substantial equivalence."

2. Sample Size and Data Provenance

• Test Set Sample Size:
  • Precision (Qualitative): 88 determinations per concentration (N=88) spread across different runs/days.
  • Method Comparison - Clinical Samples: 101 clinical unaltered samples.
• Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for an in-vitro diagnostic, these studies are typically conducted by the manufacturer in a controlled environment, likely using a mix of spiked and anonymized clinical samples. The "unaltered clinical samples" suggests prospective or retrospective collection from a clinical setting, but further details are not provided.

3. Number of Experts used to establish Ground Truth & Qualifications

• Number of Experts: Not applicable/not specified. For an immunoassay measuring a chemical compound, the "ground truth" is typically established by an independent, highly accurate analytical method, not human expert interpretation.
• Qualifications of Experts: Not applicable.

4. Adjudication Method

• Adjudication Method: Not applicable. The ground truth (confirmatory method) for chemical analysis in this context does not involve human adjudication.

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

• Was it done?: No. This type of study is relevant for imaging or interpretation-based AI systems where human readers are involved. This device is an automated immunoassay.

6. Standalone (Algorithm Only) Performance Study

• Was it done?: Yes, in a sense. The performance characteristics (precision, method comparison, interference) describe the standalone performance of the LZI Fentanyl Enzyme Immunoassay on an automated clinical chemistry analyzer (AU680 Analyzer), without human interpretation being part of the primary measurement process. The results are quantitative (ΔOD, mAU) or qualitative (positive/negative) based on predefined cutoff values.

7. Type of Ground Truth Used

• Ground Truth: For the method comparison study with clinical samples, the ground truth was established by a "more specific alternative chemical method," specifically gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS). This is considered the gold standard for confirming the presence and concentration of chemical compounds in forensic and clinical toxicology.

8. Sample Size for the Training Set

• Training Set Sample Size: Not applicable. This is a traditional immunoassay, not an AI/machine learning algorithm that requires a "training set" in that sense. The device's performance is based on its chemical and enzymatic reactions, which are inherent to its design and formulation, not learned from data. Development might involve optimizing reagents, but not "training" like an AI model.

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

• Ground Truth for Training Set: Not applicable, as there is no "training set" in the AI sense. The development of such an immunoassay involves analytical chemistry principles and empirical testing to optimize sensitivity, specificity, and other performance parameters.

Ask a specific question about this device

The LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of carisoprodol metabolite (meprobamate) in human urine at a cutoff value of 100 ng/mL when calibrated against meprobamate. The assay is designed for prescription use with a number of automated clinical chemistry analyzers.

The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for verification by a confirmatory method such as GC/MS, LC/MS or permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical result. A more specific alternative chemical confirmatory method (e.g., gas or liquid chromatography and mass spectrometry) must be used to obtain a confirmed analytical result. Clinical consideration and professional judgment must be exercised with any drug of abuse test, particularly when the preliminary test result is positive.

The LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay is a homogeneous enzyme immunoassay with ready-to-use liquid reagents. The assay is a kit comprised of two reagents (antibody/substrate reagent R1 and enzyme-drug conjugate reagent R2), which are bottled separately but sold together within the kit. The Ri solution contains mouse monoclonal anti-meprobamate antibody, glucose-6- phosphate (G6P), nicotinamide adenine dinucleotide (NAD), stabilizers, and sodium azide (0.09 %) as a preservative. The R2 solution contains meprobamate-labeled glucose-6-phosphate dehydrogenase (G6PDH) in buffer with sodium azide (0.09 %) as a preservative.

Here's a breakdown of the acceptance criteria and the study details for the LZI Carisoprodol Metabolite (Meprobamate) Enzyme Immunoassay, based on the provided document:

Acceptance Criteria and Reported Device Performance

• Positive Agreement: 98.5%
• Negative Agreement: 96.6%
  *2 false positives in "Near Cutoff Negative" (92 and 98 ng/mL, both identified as Negative by GC/MS/LC/MS)
  *1 false negative in "Near Cutoff Positive" (103 ng/mL, identified as Positive by GC/MS/LC/MS) |
  | Accuracy (Semi-Quantitative Mode) | High agreement with confirmatory method (LC/MS or GC/MS) for positive and negative samples, particularly around the cutoff. | Semi-Quantitative Analysis Agreement:
• Positive Agreement: 98.5%
• Negative Agreement: 98.3%
  *1 false positive in "Near Cutoff Negative" (98 ng/mL, identified as Negative by GC/MS/LC/MS)
  *1 false negative in "Near Cutoff Positive" (103 ng/mL, identified as Positive by GC/MS/LC/MS) |
  | Reproducibility/Precision (Qualitative Mode) | Consistent results at specific concentrations, especially near the cutoff. | At cutoff (100 ng/mL, GC/MS confirmed 94.9 ng/mL): 40 Negative / 48 Positive out of 88 determinations.
  At -25% Cutoff (75 ng/mL, GC/MS confirmed 76.8 ng/mL): 88 Negative / 0 Positive.
  At +25% Cutoff (125 ng/mL, GC/MS confirmed 122.3 ng/mL): 0 Negative / 88 Positive. |
  | Reproducibility/Precision (Semi-Qualitative Mode) | Consistent results at specific concentrations, especially near the cutoff. | At cutoff (100 ng/mL, GC/MS confirmed 94.9 ng/mL): 60 Negative / 28 Positive out of 88 determinations.
  At -25% Cutoff (75 ng/mL, GC/MS confirmed 76.8 ng/mL): 88 Negative / 0 Positive.
  At +25% Cutoff (125 ng/mL, GC/MS confirmed 122.3 ng/mL): 0 Negative / 88 Positive. |
  | Linearity/Reportable Range | Acceptable recovery across a range of concentrations. | Mean Recovery: 66.6% to 109.2% for expected concentrations from 10 ng/mL to 400 ng/mL. (Note: 10 ng/mL showed lower recovery, but higher concentrations were generally good). |
  | Analytical Specificity (Endogenous Compounds) | No interference from common endogenous compounds at specified concentrations. | No positive or negative interference observed for the listed endogenous compounds when meprobamate was at -25% or +25% of the cutoff. |
  | Analytical Specificity (Urine Preservatives) | No significant interference from common urine preservatives. | Sodium azide and sodium fluoride: No interference.
  Boric acid: Caused false negative results at +25% cutoff (125 ng/mL) and up to +125% cutoff (225 ng/mL). Labeling mitigation required. |
  | Analytical Specificity (pH) | No interference across a physiological pH range. | No positive or negative interference observed at urine pH values ranging from 3 to 11. |
  | Analytical Specificity (Specific Gravity) | No interference across a physiological specific gravity range. | No positive or negative interference observed at urine specific gravities ranging from 1.002 to 1.029. |
  | Cross-Reactivity (Structurally Related Compounds) | Acceptable cross-reactivity profile. | Carisoprodol (90.9%), Felbamate (25.0%), Meprobamate-N-Glucuronide (0.5%), Hydroxymeprobamate (0.2%). Other listed compounds showed

Ask a specific question about this device

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.

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.

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

• 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 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

Ask a specific question about this device

The LZI Oral Fluid Cannabinoids Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of Cannabinoids in neat human oral fluid, collected into the LZI Oral Fluid THC Collector, at the cut-off value of 4 ng/mL with △9- tetrahydrocannabinol (THC) as calibrators. The assay is designed for prescription use with a number of 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 GCMS and LCMS or (2) permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical result. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas or liquid 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 Oral Fluid Cannabinoids Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oral Fluid Cannabinoids Enzyme Immunoassay at the cut-off value of 4 ng/mL.

The LZI Oral Fluid Cannabinoids Controls are for use as assayed quality control materials to monitor the precision of the LZI Oral Fluid Cannabinoids Enzyme Immunoassay at the cut-off value of 4 ng/mL.

The LZI Oral Fluid Cannabinoids assay is a homogeneous enzyme immunoassay with ready-touse liquid reagent. The assay is based on competition between drug in the sample and drug 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 drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, cannabinoid derivative-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when free drug is present in the sample, antibody would bind to free drug, the unbound cannabinoid derivative-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 Oral Fluid Cannabinoids 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-Cannabinoids antibody, glucose-6-phosphate (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 Cannabinoids, stabilizers, in buffer with sodium azide (0.09%) as preservative.

The LZI Oral Fluid Cannabinoids Enzyme Immunoassay calibrators and controls designated for use at the 4 ng/mL cutoffs contain 0, 2, 3, 4, 5, 6, and 12 ng/mL of Δ'-tetrahydrocannabinol (THC) in synthetic oral fluid with sodium azide (0.09%) as preservative. These five calibrators and two controls are sold as individual bottles.

The provided text describes the LZI Oral Fluid Cannabinoids Enzyme Immunoassay, its acceptance criteria, and the studies performed to demonstrate its performance.

Here's the breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a separate section. However, the performance characteristics provided, particularly the "Method Comparison: Clinical Samples" and "Precision" data, implicitly define the expected performance for qualitative and semi-quantitative results against a confirmatory method (GC/MS).

Given the information, the acceptance criteria can be inferred as a high concordance between the immunoassay and the GC/MS reference method, especially for distinguishing between positive and negative samples around the 4 ng/mL cutoff. For specific values, the "Precision" tables show the expected ranges of positive/negative results at various concentrations relative to the cutoff.

Here's a table summarizing the reported device performance, inferring acceptance based on achieving high concordance:

2. Sample size used for the test set and the data provenance:

• Test Set Sample Size: 42 positive and 41 negative unaltered oral fluid samples, totaling 83 samples.
• Data Provenance: Not explicitly stated regarding country of origin. The study appears to be retrospective as samples were collected and then evaluated. The samples were collected using the "LZI Oral Fluid Collector."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

• The ground truth was established by Gas or Liquid Chromatography/mass spectrometry (GC/MS or LC/MS), which is described as the "preferred confirmatory method." This is a laboratory analytical technique, not a human expert judgment. Therefore, the concept of "number of experts" is not applicable in this context.

4. Adjudication method for the test set:

• No adjudication method involving human experts is described since the ground truth was established by GC/MS. The immunoassay results were directly compared to the GC/MS quantitative values.

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:

• No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) assay for drug detection, not an AI-assisted diagnostic tool that would typically involve human readers interpreting results.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

• Yes, a standalone performance study was done. The LZI Oral Fluid Cannabinoids Enzyme Immunoassay is an automated assay designed for use with clinical chemistry analyzers (e.g., Beckman AU400e). Its performance (precision, method comparison) was evaluated directly as the algorithm/assay only, without human interpretation factored into the core performance metrics presented. While a human might interpret the final positive/negative result, the performance data itself is of the device in isolation.

7. The type of ground truth used:

• The ground truth used was analytical confirmation by Gas Chromatography/Mass Spectrometry (GC/MS). This is a highly specific and sensitive laboratory method considered the "gold standard" for confirming drug presence and concentration.

8. The sample size for the training set:

• The document does not provide information on a training set size. The LZI Oral Fluid Cannabinoids Enzyme Immunoassay is a chemical assay (enzyme immunoassay), not a machine learning or AI algorithm that typically requires a distinct training dataset. Its development would involve chemical optimization and characterization rather than algorithm training.

9. How the ground truth for the training set was established:

• As there's no explicit mention of a training set in the context of an AI/ML algorithm, this question is not applicable in the same way it would be for an AI device. The "ground truth" for developing such an assay would involve known concentrations of target analytes and cross-reactants to characterize the assay's chemical behavior.

Ask a specific question about this device