(224 days)
Immunalysis Tramadol Urine Enzyme Immunoassay:
The Immunalysis Tramadol Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 200ng/ mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Tramadol in human urine with automated clinical chemistry analyzers. This assay is calibrated against Tramadol. 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 GC-MS or permitting laboratories to establish quality control procedures. The test is not intended to differentiate between drugs of abuse and prescription use of Tramadol. There are no uniformly recognized drug levels for Tramadol in urine.
The Immunalysis Tramadol Urine Enzyme Immunoassay Kit provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectroscopy (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 Tramadol Urine Controls:
The Immunalysis Tramadol Urine Controls are used as control materials in the Immunalysis Tramadol Urine Enzyme Immunoassay.
Immunalysis Tramadol Urine Calibrators:
The Immunalysis Tramadol Urine Calibrators are used as calibrators in the Immunalysis Tramadol Urine Enzyme Immunoassay for the qualitative and semi-quantitative determination of Tramadol in urine on automated clinical chemistry analyzers.
The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes goat antibodies to Tramadol, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. The enzyme conjuqate reagent includes tramadol derivative labeled with qlucose-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 tramadol calibrator and controls consists of a single calibrator at 200ng/mL, a control set containing a LOW control at 150ng/mL and a HIGH control at 250ng/mL and a calibrator set containing a negative calibrator, a Level 1 calibrator at 100ng/mL, a Level 2 calibrator at 200ng/mL, a Level 3 calibrator at 500ng/mL and a Level 4 calibrator at 1000nq/mL.
The document describes the Immunalysis Tramadol Urine Enzyme Immunoassay and its performance characteristics. The study aimed to demonstrate substantial equivalence to a predicate device.
Here's the breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined "acceptance criteria" in a separate table. Instead, it presents study results which implicitly serve as performance metrics that demonstrate the device's acceptable function. The "Result" column in the tables below indicates the device's performance against expected outcomes at various concentrations/conditions.
| Study | Acceptance Criteria (Implicit from Study Design) | Reported Device Performance (Summary) |
|---|---|---|
| Qualitative Analysis (200ng/mL cutoff) | Correct classification of samples relative to the 200ng/mL cutoff. | At -100% to -25% of cutoff (0-150 ng/mL): 80/80 Negative. |
| At cutoff (200 ng/mL): 44 Negative / 36 Positive (demonstrating boundary function). | ||
| At +25% to +100% of cutoff (250-400 ng/mL): 80/80 Positive. | ||
| Semi-Quantitative Analysis (200ng/mL cutoff) | Correct classification and semi-quantitative results relative to the 200ng/mL cutoff. | At -100% to -25% of cutoff (0-150 ng/mL): 80/80 Negative. |
| At cutoff (200 ng/mL): 47 Negative / 33 Positive (demonstrating boundary function). | ||
| At +25% to +100% of cutoff (250-400 ng/mL): 80/80 Positive. | ||
| Specificity and Cross-Reactivity (Qualitative) | Correct classification of structurally similar and non-similar compounds at specified concentrations. | Tramadol (200ng/mL): 100% Cross-Reactivity. |
| n-Desmethyl Tramadol (450ng/mL): POS, 44.4% Cross-Reactivity. | ||
| o-Desmethyl Tramadol (25000ng/mL): POS, 0.8% Cross-Reactivity. | ||
| Venlafaxine/o-Desmethyl Venlafaxine (100,000ng/mL): NEG, N.D. | ||
| Specificity and Cross-Reactivity (Semi-Quantitative) | Correct classification and semi-quantitative results for structurally similar and non-similar compounds. | Tramadol (200ng/mL): 100% Cross-Reactivity. |
| n-Desmethyl Tramadol (450ng/mL): 44.4% Cross-Reactivity. | ||
| o-Desmethyl Tramadol (25000ng/mL): 0.8% Cross-Reactivity. | ||
| Venlafaxine/o-Desmethyl Venlafaxine (100,000ng/mL): N.D. | ||
| Interference (Structurally Non-Similar Compounds) | No interference (Negative results for -25% cutoff, Positive for +25% cutoff). | For most compounds tested (e.g., 6-Acetylcodeine, Alprazolam, Caffeine, Cocaine, Codeine, etc.): Negative at -25% cutoff (150ng/mL) and Positive at +25% cutoff (250ng/mL), indicating no interference. |
| Interference (Endogenous Compounds) | No interference (Negative results for -25% cutoff, Positive for +25% cutoff). | For most compounds tested (e.g., Acetone, Ascorbic Acid, Creatinine, Ethanol, Glucose, Urea, etc.): Negative at -25% cutoff (150ng/mL) and Positive at +25% cutoff (250ng/mL), indicating no interference. |
| Boric Acid (1% w/v): Negative at both -25% and +25% cutoff, indicating interference. (Note: This interference was acknowledged and added to labeling). | ||
| Interference (Effect of pH) | No interference within the physiological pH range. | pH 3.0 to 11.0: Negative at -25% cutoff (150ng/mL) and Positive at +25% cutoff (250ng/mL), indicating no interference. |
| Interference (Effect of Specific Gravity) | No interference across a range of specific gravities. | Specific Gravity 1.000 to 1.030: Negative at -25% cutoff (150ng/mL) and Positive at +25% cutoff (250ng/mL), indicating no interference. |
| Linearity/Recovery | Recovery percentage within an acceptable range across the expected concentration range. | Recovery %: Ranged from 94% to 110% across concentrations of 50 ng/mL to 1100 ng/mL. |
| Method Comparison (Qualitative) | High agreement with LC/MS confirmation for positive and negative samples. | Positive: 100% agreement (100 samples). |
| Negative: 100% agreement (50 samples). | ||
| Overall Agreement (%): 100% for both positive and negative categories at various concentration ranges. | ||
| Method Comparison (Semi-Quantitative) | High agreement with LC/MS confirmation for positive and negative samples. | Positive: 100% agreement (100 samples). |
| Negative: 100% agreement (50 samples). | ||
| Overall Agreement (%): 100% for both positive and negative categories at various concentration ranges. | ||
| Stability (Closed Accelerated Reagents) | Continued performance within specifications over time. | Qualitative & Semi-Quantitative: Levels 0 & 150 ng/mL consistently negative; 250 ng/mL consistently positive up to 40 days (accelerated). Supports 1-year expiration. |
| Stability (Open/On-board Reagents) | Continued performance within specifications when opened and on-board. | Qualitative & Semi-Quantitative: Levels 150 ng/mL consistently negative; 250 ng/mL consistently positive up to 28 days. Supports 28-day open vial expiration. |
| Stability (Specimen and Storage Handling) | Stable performance of specimens over time under storage conditions. | MS data: Specimen below cutoff consistently negative; specimen above cutoff consistently positive for Day 0, Week 1, 2, 3, and 4. Supports 1-month storage at 2-8°C. |
| Stability (Calibrator and Control - Open Accelerated) | Stable performance of calibrators and controls over time. | All calibrator and control levels: Within specifications for Day 0, 3, 7, 10, and 13. Supports 6-month open vial expiration. |
| Calibrator and Control Traceability & Value Assignment | Traceability to commercial standards and accurate value assignment via mass spectrometry. | All components traced to Cerilliant Chemicals standard. Calibrators/controls adjusted and retested by mass spectrometry until within acceptable ranges. |
2. Sample Sizes Used for the Test Set and Data Provenance
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Precision/Cutoff Characterization Study: N=80 for each concentration level (0, 50, 100, 150, 200, 250, 300, 350, 400 ng/mL). This involved 20 days, 2 runs per day, in duplicate.
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Specificity and Cross-Reactivity: Not explicitly stated but implies testing of individual compounds at specified concentrations.
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Interference (Structurally Non-Similar Compounds, Endogenous Compounds, pH, Specific Gravity): Not explicitly stated, but each potential interferent was tested at two concentrations (-25% and +25% of cutoff). This is typically performed on multiple replicates.
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Linearity/Recovery: 13 different concentrations were prepared and tested.
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Method Comparison: 100 positive samples and 50 negative samples were analyzed.
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Stability Studies:
- Closed Accelerated Stability: Tested at various time points (Day 0, 2, 8, 16, 24, 32, 40) for 0, 150, 250 ng/mL levels.
- Open/On-board Stability: Tested at various time points (Day 0, 7, 14, 21, 28) for 150, 250 ng/mL levels (all replicates).
- Specimen and Storage Handling: Tested at various time points (Day 0, Week 1, 2, 3, 4) for one specimen below cutoff and one above cutoff.
- Calibrator and Control Stability: Tested at various time points (Day 0, 3, 7, 10, 13) for all 4 calibrator levels and 2 control levels.
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Data Provenance: The document states that for the Method Comparison study, "Unaltered, anonymous and discarded clinical urine samples obtained from clinical testing laboratories were analyzed with the test device." This indicates the data is retrospective and derived from a clinical laboratory setting, but the specific country of origin is not mentioned. For other studies, samples were prepared in the laboratory (e.g., drug-free urine spiked with analytes).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
- Ground Truth Establishment: For the method comparison study, "Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectroscopy (LC/MS) is the preferred confirmatory method." The document explicitly states that the device's performance was "verified by Mass Spectrometry" and LC/MS was used. LC/MS is an analytical gold standard, performed by trained laboratory personnel.
- Number of Experts/Qualifications: The document does not specify human experts or their qualifications for establishing ground truth; instead, it relies on the results from the confirmatory analytical method (LC/MS).
4. Adjudication Method for the Test Set
- Given that the ground truth for the method comparison study was established by LC/MS, an objective analytical method, there was no need for a human adjudication method (e.g., 2+1, 3+1). The LC/MS result is considered the definitive truth.
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 device is an in-vitro diagnostic device (immunoassay) intended for use with automated clinical chemistry analyzers, not for human interpretation of medical images or other subjective assessments. Therefore, the concept of "human readers improving with AI vs without AI assistance" is not applicable here.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Yes, the entire study effectively demonstrates the standalone performance of the Immunalysis Tramadol Urine Enzyme Immunoassay. It is an automated assay run on a Beckman Coulter AU 400e (an automated clinical chemistry analyzer). The results presented are the output of the algorithm/assay itself, with LC/MS serving as the independent gold standard for comparison. The device is intended to provide a preliminary analytical test result.
7. The Type of Ground Truth Used
- The ground truth used for the method comparison study was confirmatory analytical testing, specifically Liquid Chromatography / Mass Spectroscopy (LC/MS). For other performance studies (e.g., precision, cross-reactivity, interference), ground truth was established by precise preparation and spiking of samples with known concentrations of analytes.
8. The Sample Size for the Training Set
- This is an in-vitro diagnostic (IVD) immunoassay kit. IVD assays are developed through chemical and biological formulation and optimization, not typically through machine learning or AI algorithms that require "training sets" in the conventional sense. Therefore, the concept of a "training set" as understood in AI/ML is not applicable here. The reagent formulation and assay parameters are chemically and biochemically defined and validated, not "trained" on a data set.
9. How the Ground Truth for the Training Set Was Established
- As explained in point 8, there isn't a "training set" in the AI/ML sense for this type of device. The ground truth for the development and optimization of the immunoassay itself would come from standard analytical chemistry principles, characterization of antibody binding, enzyme kinetics, and comparison to established reference standards during the formulation process. For example, calibrators are prepared and validated against commercially available standard solutions (Cerilliant Chemicals, as mentioned in the document).
§ 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).