(58 days)
The Immunalysis Amphetamine Urine Enzyme Immunoassay Kit is a homogeneous enzyme immunoassay with dual cutoffs of 500 ng/mL and 1000 ng/mL. The assay is intended for use in laboratories for the qualitative and semiquantitative analysis of Amphetamine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Amphetamine. This in-vitro 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 GC-MS or permitting laboratories to establish quality control procedures.
The Immunalysis Amphetamine 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. Gas Chromatography/Mass Spectrometry (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.
Immunalysis Amphetamine Urine Controls: The Immunalysis Amphetamine Urine Control materials in Immunalysis Amphetamine Urine Enzyme Immunoassay.
Immunalysis Amphetamine Urine Calibrators: The Immunalysis Amphetamine Urine Calibrators in the Immunalysis Amphetamine Urine Enzyme Immunoassay. for the qualitative and semi-quantitative determination of Amphetamine in urine on automated clinical chemistry analyzers.
The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes monoclonal antibodies to Amphetamine, glucose-6phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes amphetamine derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with Sodium Azide as a preservative. Calibrators and controls are sold separately. Reagents are liquid, ready to use
The amphetamine calibrator and controls consist of dual cutoff calibrators at 500ng/mL and 1000ng/mL, a control set containing a LOW control at 375ng/mL and a HIGH control at 625ng/mL for the 500ng/mL cutoff and a LOW control at 750ng/mL and HIGH control at 1250ng/mL for the 1000ng/mL cutoff, and a calibrator set containing a negative calibrator, a Level 1 calibrator at 500ng/mL, a Level 2 calibrator at 1000ng/mL, a Level 3 calibrator at 1500ng/mL, and a Level 4 calibrator at 2000ng/mL.
The Immunalysis Amphetamine Urine Enzyme Immunoassay, along with its calibrators and controls, is intended for the qualitative and semi-quantitative analysis of Amphetamine in human urine using automated clinical chemistry analyzers. The assay offers dual cutoffs of 500 ng/mL and 1000 ng/mL. The semi-quantitative mode is used to determine appropriate specimen dilution for confirmation by methods like GC-MS or LC/MS. The device is for prescription use only and provides a preliminary analytical result, requiring a more specific alternate chemical method for confirmation.
Here's an overview of the acceptance criteria and the studies that prove the device meets them:
1. Table of Acceptance Criteria & Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a structured table. However, the performance studies implicitly define the criteria for acceptable performance in each category. The reported device performance is presented in summarized tables for each study.
| Study Area | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Precision/Cutoff Characterization | Qualitative results should correctly identify samples as negative or positive relative to the cutoff, with minimal indeterminate results at the cutoff. | 500 ng/mL cutoff: |
| - At 0, 125, 250, 375 ng/mL (negative range), all 80 determinations were Negative. | - At 0, 125, 250, 375 ng/mL: 80 Negative | |
| - At 625, 750, 875, 1000 ng/mL (positive range), all 80 determinations should be Positive. | - At 500 ng/mL (Cutoff): 48 Negative / 32 Positive | |
| - At the cutoff (500 ng/mL or 1000 ng/mL), a mix of negative and positive results is expected reflecting the boundary. | - At 625, 750, 875, 1000 ng/mL: 80 Positive | |
| 1000 ng/mL cutoff: | ||
| - At 0, 250, 500, 750 ng/mL: 80 Negative | ||
| - At 1000 ng/mL (Cutoff): 47 Negative / 33 Positive | ||
| - At 1250, 1500, 1750, 2000 ng/mL: 80 Positive | ||
| Specificity/Cross-Reactivity | Structurally similar compounds should exhibit expected levels of cross-reactivity, and structurally non-similar compounds should show no interference. | Demonstrated specified cross-reactivity percentages for similar compounds and "No Interference" for non-similar compounds, endogenous compounds, Boric Acid, and various pH/specific gravity levels. (See tables 5-18 in the document for detailed performance). |
| Interference | Exogenous (non-similar compounds, Boric Acid) and endogenous compounds, as well as variations in pH and specific gravity, should not lead to false positive or false negative results around the cutoff values. | All tested compounds and conditions: No Interference for both -25% and +25% of cutoff concentrations when tested against potentially interfering substances, various pH levels (3.0-11.0), and specific gravity levels (1.000-1.030). (See tables 9-18 in the document for detailed performance). |
| Linearity/Recovery | The assay should demonstrate linearity and acceptable recovery across a range of amphetamine concentrations in the semi-quantitative mode. | Mean Recovery across a range of 200 ng/mL to 2200 ng/mL varied between 76.2% and 107.1% (Table 19). |
| Method Comparison | High agreement (e.g., 100% or near 100%) between the test device results and confirmed LC/MS results. | 500 ng/mL cutoff (Qualitative & Semi-quantitative): 100% agreement between test device and LC/MS (40 positive, 40 negative). |
| 1000 ng/mL cutoff (Qualitative & Semi-quantitative): 98% agreement. One discordant sample (Sample ID 395246ZA) was negative by the test device but confirmed at 1173 ng/mL by LC/MS (above the 1000 ng/mL cutoff, representing a false negative by the device at this specific instance for semi-quantitative). | ||
| Stability | Assays, calibrators, and controls should remain stable for a specified duration under defined storage conditions. | 1-year expiration date for reagents (closed accelerated stability to 25℃). 12-month expiration for calibrators and controls (closed accelerated stability to 25℃). 28-day open vial expiration for reagents (on-board stability at 2℃ to 8℃). 6-month open vial expiration for calibrators and controls (accelerated stability at 25℃). Real-time stability studies are ongoing. |
2. Sample Sizes used for the Test Set and Data Provenance:
- Precision/Cutoff Characterization Study: 80 determinations for each concentration level tested (20 days, 2 runs per day, in duplicate).
- Specificity and Cross-Reactivity: Not explicitly stated as a "sample size" of unique patient samples, but each specified compound was spiked into "drug free urine" at various concentrations.
- Interference: Similarly, not a "sample size" of unique patient samples, but various potential interferents (structurally non-similar compounds, endogenous compounds, Boric Acid) were spiked into "drug free urine" containing the target analyte at ±25% of the cutoff. pH and Specific Gravity effects were also evaluated under these conditions.
- Linearity/Recovery: Not explicitly stated as a "sample size" of unique patient samples, but serial dilutions were made from a "drug free urine pool" spiked with a high concentration of the target analyte.
- Method Comparison: 80 clinical urine samples (40 positive, 40 negative) for the 500 ng/mL cutoff and 81 clinical urine samples (41 positive, 40 negative) for the 1000 ng/mL cutoff.
- Data Provenance: The Method Comparison study used "Unaltered, anonymous and discarded clinical urine samples obtained from clinical testing laboratories." The country of origin is not specified but is implicitly the USA, given the FDA submission. The data is retrospective, as it used discarded clinical samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
- Ground truth for Method Comparison: The ground truth was established by Mass Spectrometry, specifically using an Agilent 6430 Liquid Chromatography Tandem Mass Spectrometry (LC/MS). This is an objective analytical method and does not involve human expert consensus for interpretation in the same way, for example, a radiologist would interpret an image. Therefore, the concept of "number of experts" or "qualifications of experts" as typically applied to imaging studies does not directly apply here.
4. Adjudication Method for the Test Set:
- Not applicable in the conventional sense. The "ground truth" for the method comparison study was established by LC/MS, which is a definitive chemical analysis method, not requiring a human adjudication process to resolve disagreements between readers/interpreters.
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 typically involves multiple human readers interpreting medical images or other diagnostic tests, sometimes with and without AI assistance, to assess the AI's impact on human performance. The current document describes an in-vitro diagnostic device for chemical analysis of urine, which does not involve human readers interpreting complex cases in the same manner as an MRMC study.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance presented for the Immunalysis Amphetamine Urine Enzyme Immunoassay is the standalone performance of the algorithm/device. The device automatically analyzes urine samples and provides qualitative and semi-quantitative results. Human involvement is in operating the automated clinical chemistry analyzer and interpreting the final quantitative values against cutoffs, but the core "performance" data (e.g., precision, cross-reactivity, method comparison against LC/MS) reflects the device's inherent analytical capabilities without a human interpretation step influencing the reported results in the study itself.
7. The Type of Ground Truth Used:
- For the analytical performance studies (Precision, Specificity, Interference, Linearity), the ground truth was based on known concentrations of spiked analytes in drug-free urine.
- For the Method Comparison study, the ground truth was established by a confirmatory method: Liquid Chromatography/Mass Spectrometry (LC/MS). This is a highly sensitive and specific analytical technique considered the gold standard for confirming drug presence and concentration in urine.
8. The Sample Size for the Training Set:
- The document does not report on a training set in the context of an "algorithm" that needs to be "trained." This is an in-vitro diagnostic immunoassay kit, which relies on chemical reactions and optical readings rather than machine learning algorithms trained on large datasets. Therefore, the concept of a "training set" for an AI model is not applicable here. The device is fundamentally a chemical measurement system.
9. How the Ground Truth for the Training Set Was Established:
- As stated above, this device is a chemical immunoassay, not an AI/ML algorithm requiring a training set. Therefore, this question is not applicable.
§ 862.3100 Amphetamine test system.
(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine 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).