(86 days)
The Immunalysis Methamphetamine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 500ng/mL and 1000ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Methamphetamine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Methamphetamine. This in-vitro diagnostic device is for prescription use only.
The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or permitting laboratories to establish quality control procedures.
The Immunalysis Methamphetamine Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical must be used in order to obtain a confirmed analytical result. GC-MS or Liquid Chromatography / Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.
The Immunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine, Morphine, PCP and Oxazepan. The calibrators are designed for prescription use with immunoassays.
The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes monoclonal antibodies to Methamphetamine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Methamphetamine derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with Sodium Azide as a preservative.
All of the Immunalysis Multi-Drug Calibrators are liquid and ready to use. Each contains a known concentration of a specific drug analyte as a mixture.
The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators are prepared by spiking known concentrations of drug analyte into the negative calibrator matrix. These five calibrators (negative, Level 1, 2, 3 and 4) are sold as individual bottles.
Here's an analysis of the provided text regarding the Immunalysis Methamphetamine Urine Enzyme Immunoassay and its performance, structured according to your request:
Device: Immunalysis Methamphetamine Urine Enzyme Immunoassay & Immunalysis Multi-Drug Calibrators
Intended Use: Qualitative and semi-quantitative analysis of Methamphetamine in human urine with automated clinical chemistry analyzers at dual cutoffs of 500ng/mL and 1000ng/mL. For prescription use.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate, quantitative target alongside its performance study results. Instead, the studies demonstrate the device's performance, implying that these results meet implicit acceptance criteria for substantial equivalence to the predicate device. For the purpose of this table, I will infer the acceptance criteria from the observed performance and the nature of these types of immunoassays (i.e., that they should accurately classify samples around the cutoff and show no significant interference).
| Performance Study Category | Implicit Acceptance Criteria (Inferred) | Reported Device Performance (as presented in the document) |
|---|---|---|
| 1. Precision/Cutoff Characterization | All determinations at concentrations ≥+25% of cutoff should be positive; all determinations at concentrations ≤-25% of cutoff should be negative. ~50% positive/negative at cutoff. | 500ng/mL qualitative: 95%) with LC/MS confirmation for both positive and negative samples at both cutoffs. |
| Qualitative (1000ng/mL): 100% agreement (40 Pos, 40 Neg) with LC/MS. | ||
| Semi-quantitative (500ng/mL): 98% positive agreement (40/41 total positive by LC/MS), 100% negative agreement (39/39 total negative by LC/MS). One discordant result. | ||
| Semi-quantitative (1000ng/mL): 100% positive agreement (39/39 total positive by LC/MS), 98% negative agreement (40/41 total negative by LC/MS). One discordant result. | ||
| One discordant sample at 500ng/mL cutoff (device positive, LC/MS 494ng/mL - close to cutoff). One discordant sample at 1000ng/mL cutoff (device negative, LC/MS 1017ng/mL - close to cutoff). |
2. Sample Size Used for the Test Set and Data Provenance
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Precision/Cutoff Characterization (Tables 3-6):
- Test set size: 80 determinations at each of 9 concentration levels per cutoff (0, -75%, -50%, -25%, Cutoff, +25%, +50%, +75%, +100%). This means 80 samples were prepared at each concentration level. The study was performed for 20 days, 2 runs per day in duplicate.
- Data Provenance: Drug-free urine spiked with methamphetamine. This is prospective data (laboratory prepared). The country of origin is not explicitly stated but implies a US-based laboratory testing context (given the FDA submission).
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Specificity and Cross-Reactivity (Tables 7-10) and Interference (Tables 11-18) including pH and Specific Gravity:
- Test set size: Not explicitly stated as a count of individual samples for each compound, but results are given for individual compounds at specific concentrations. The implication from the precision study (80 determinations per concentration) might suggest similar rigorous testing for these as well, but it's not confirmed. The overall approach is that each compound was "spiked into drug free urine."
- Data Provenance: Drug-free urine spiked with relevant compounds. This is prospective (laboratory prepared).
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Method Comparison (Tables 24-33):
- Test set size: 80 human urine samples (referred to as "clinical urine samples").
- Data Provenance: "Eighty unaltered, anonymous and discarded clinical urine samples obtained from clinical testing laboratories." This indicates retrospective data from clinical settings. The country of origin for these samples is not explicitly stated but is implied to be within the US given the context of FDA submission.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- For the Precision/Cutoff Characterization, Specificity/Cross-Reactivity, and Interference studies, the ground truth was established by laboratory spiking of known concentrations of methamphetamine or other compounds into drug-free urine. No human experts were required to establish this ground truth. The spiked concentrations were "confirmed by mass spectrometry (MS)."
- For the Method Comparison study, the ground truth was established by Mass Spectrometry (LC-MS/MS), which is the "preferred confirmatory method" as stated in the Indications for Use. This is an objective analytical method, not reliant on human expert interpretation.
4. Adjudication Method for the Test Set
Not applicable. The ground truth for the analytical studies was established by spiking known concentrations (laboratory-prepared) and confirmed by Mass Spectrometry (objective analytical method), not by human adjudication of qualitative results.
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 device is an in-vitro diagnostic immunoassay for detecting substances in urine, not an AI-assisted diagnostic imaging or interpretation tool for human readers. Therefore, an MRMC study related to human improvement with AI assistance is not relevant or described.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, this entire study represents a standalone "algorithm only" (device only) performance evaluation. The Immunalysis Methamphetamine Urine Enzyme Immunoassay is an automated clinical chemistry analyzer assay, meaning its output is directly read from the analyzer, without human interpretation of raw data for the primary qualitative or semi-quantitative result. The "human-in-the-loop" would be a lab technician running the sample and interpreting the final pass/fail result based on the analyzer's output relative to the cutoff, but the core performance data presented is the device's direct measurement.
7. The Type of Ground Truth Used
- Precision/Cutoff Characterization, Specificity/Cross-Reactivity, Interference (including pH, specific gravity, Boric Acid): Laboratory-prepared samples with known, spiked concentrations confirmed by Mass Spectrometry (MS).
- Method Comparison: LC-MS/MS confirmation (Liquid Chromatography / Mass Spectrometry), which is considered the "gold standard" or preferred confirmatory method for drug testing.
8. The Sample Size for the Training Set
The document describes performance studies for the Immunalysis Methamphetamine Urine Enzyme Immunoassay. For an immunoassay of this type, the "training set" doesn't typically refer to a data set used to train a machine learning model. Instead, it refers to the reagents and their formulation which are developed and optimized internally by the manufacturer. The document does not provide details on the development (analogous to 'training') data or processes. The reported studies are validation studies demonstrating the final product's performance.
9. How the Ground Truth for the Training Set Was Established
As explained above, for an immunoassay, the concept of a "training set" and establishing its ground truth in the context of machine learning is not directly applicable. The "ground truth" for the calibrators (part of the device, analogous to some aspects of training or reference) is detailed:
- Immunalysis Multi-Drug Calibrators: "Calibrators are manufactured and are tested by mass spectrometry."
- Negative calibrator: "processed, drug free urine matrix... compared to a reference negative standard to ensure that it is free of analyte."
- Non-zero calibrators: "prepared by spiking a known concentration of oxazepam in the negative calibrator matrix."
- "If any of the analytes are not of the acceptable range, then the calibrator is adjusted and re-tested. Values are assigned to the calibrators once the mass spectrometry results are within the acceptable ranges."
This means the ground truth for the calibrators is established through controlled spiking of known concentrations and verification by mass spectrometry.
§ 862.3610 Methamphetamine test system.
(a)
Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.(b)
Classification. Class II (special controls). A methamphetamine 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).