(58 days)
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
| Acceptance Criteria Category | Specific Acceptance Criteria (Inferred from study design) | Reported Device Performance and Study Results |
|---|---|---|
| Precision | Consistent results (negative/positive) for samples at various concentrations around the cutoff. For 100 ng/mL cutoff, typically 100% agreement for concentrations ± 25% and 100% agreement for concentrations further from cutoff, with some expected variability at the cutoff itself. | Within Run (N=22 determinations): |
- 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
| Acceptance Criteria Category | Specific Acceptance Criteria (Inferred from study design) | Reported Device Performance and Study Results |
|---|---|---|
| Precision | Consistent results (negative/positive) for samples at various concentrations around the cutoff. For 300 ng/mL cutoff, similar criteria as above. | Within Run (N=22 determinations): |
- 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.
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).