(56 days)
BIOEASY Multi-Drug Test Cup Tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Oxazepam, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxy-methamphetamine, Phencyclidine, Methadone, Nortriptyline and d-Propoxyphene in human urine at the cutoff concentrations of:
| Drug(Identifier) | Cut-off level |
|---|---|
| Amphetamine | 1000 ng/mL |
| Oxazepam | 300 ng/mL |
| Cocaine | 300 ng/mL |
| Marijuana | 50 ng/mL |
| Methamphetamine | 1000 ng/mL |
| Morphine | 300 ng/mL |
| Oxycodone | 100 ng/mL |
| Secobarbital | 300 ng/mL |
| Buprenorphine | 10 ng/mL |
| Methylenedioxy-methamphetamine | 500 ng/mL |
| Phencyclidine | 25 ng/mL |
| Methadone | 300 ng/mL |
| Nortriptyline | 1000 ng/mL |
| d-Propoxyphene | 300 ng/mL |
Configuration of the BIOEASY Multi-Drug Test Cup tests can consist of any combination of the above listed drug analytes.
The test may yield positive results for the prescription drugs Buprenorphine, Nortriptyline, Oxazepam, Secobarbital, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.
For in vitro diagnostic use only.
The BIOEASY Multi-Drug Test Cup tests are immunochromatographic assays that use a lateral flow system for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital, Buprenorphine, Methylenedioxymethamphetamine, Phencyclidine, Methadone, Nortriptyline and Propoxyphene (target analytes) in human urine. The products are single-use in vitro diagnostic devices. Each test kit contains a Test Device, a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch
Here's an analysis of the acceptance criteria and the study that proves the device meets the acceptance criteria, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the successful outcomes of the various performance studies. The reported device performance is excellent, demonstrating near-perfect agreement with the LC/MS ground truth for samples outside the +/-25% cutoff range, and reasonable agreement within the +/-25% cutoff range, which is expected for qualitative tests around the cutoff.
| Acceptance Criteria Category | Specific Acceptance Criteria (Inferred) | Reported Device Performance Summary |
|---|---|---|
| Precision | Consistent and accurate results across different lots and concentrations. | For -100% to -25% of cutoff: 100% negative results. For +25% to +100% of cutoff: 100% positive results. At cutoff: varying split between positive/negative (e.g., Amphetamine Lot 1: 23-/27+), which is expected for qualitative assays at the decision point. |
| Stability | Device remains effective for its stated shelf life. | Stable at 4-30 °C for 24 months (accelerated stability). Real-time studies ongoing. |
| Interference | No significant interference from common physiological/pathological substances. | No interference observed for a wide range of common substances at specified concentrations (summarized in tables on page 9-10). |
| Specificity (Cross-reactivity) | Correct identification of target drugs/metabolites, with acceptable cross-reactivity to similar compounds. | Detailed cross-reactivity tables provided for each drug, showing specificity to the target analyte and acceptable cross-reactivity percentages for related compounds (pages 10-13). |
| Effect of Urine Specific Gravity & pH | Performance unaffected by variations in urine specific gravity and pH. | No differences observed for samples at +/-25% cut-off levels with specific gravity from 1.000 to 1.035 and pH 4-9. |
| Method Comparison (Professional User) | High agreement with LC/MS reference method. | For each drug, out of 80 samples (40 negative, 40 positive), most samples outside the near cut-off range were correctly identified. Discordant results primarily occurred in the near cut-off positive/negative ranges, where the device correctly identified values slightly above the cutoff as positive and slightly below as negative in many cases, even when LC/MS showed a value across the cutoff. Overall strong agreement. |
| Lay-user Study | High percentage of correct results by untrained users, and ease of understanding instructions. | For -100% to -50% of cutoff: 100% correct negative results. For +50% to +100% of cutoff: 100% correct positive results. At -25% and +25% of cutoff: 95% correct results for most drugs, with Nortriptyline at +25% having 90%. All lay users found instructions easy to follow, and Flesch-Kincaid score indicated Grade Level 7 reading. |
2. Sample Size Used for the Test Set and Data Provenance
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Precision Studies:
- For each of the 14 analytes, 8 concentrations were tested (ranging from -100% cut off to +100% cut off).
- For each concentration, tests were performed two runs per day for 25 days, using 3 different lots of the device.
- Total samples per lot per concentration: 50 (2 runs/day * 25 days).
- Total samples per drug per concentration for 3 lots: 150 (50 * 3 lots).
- Total samples per drug: 1,200 (150 * 8 concentrations).
- Total samples for all 14 drugs in precision study: 16,800.
- Data Provenance: The text does not explicitly state the country of origin but implies it was performed "in-house" by the manufacturer (Shenzhen Bioeasy Biotechnology Co., Ltd. in China). These samples were prepared by spiking drug in negative samples. The study appears to be prospective in nature for the purpose of device validation.
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Interference & Specificity Studies:
- "Three batches of each device" were used.
- The number of individual samples tested for each interfering substance or cross-reactant is not explicitly stated, but it involved "drug-free urine and target drugs urine with concentrations at 25% below and 25% above Cut-Off levels."
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Effect of Urine Specific Gravity and pH:
- "Three lots of each device" were used.
- "Urine samples, with 1.000 to 1.035 specific gravity or urine samples with pH 4 to 9 were spiked with target drugs at 25% below and 25% above Cut-Off levels." The exact number of samples at each specific gravity/pH level is not detailed.
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Method Comparison (Professional User) Studies:
- For each of the 14 analytes: 80 unaltered clinical samples (40 negative and 40 positive).
- Total samples for 14 drugs: 1120 samples.
- Data Provenance: "clinical samples" are mentioned, but their country of origin is not specified. The study is retrospective, as these are "unaltered clinical samples" compared to LC/MS results.
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Lay-user Study:
- 300 lay persons were involved.
- The text describes sample numbers for various concentrations. For each drug, a total of 300 samples were prepared the following way: 20 at -100% Cutoff, 20 at -75%, 160 at -50%, 20 at -25%, 20 at +25%, 40 at +50%, 20 at +75%.
- Total samples per drug: 300.
- Total samples for all 14 drugs in lay-user study: 4,200.
- Data Provenance: The text does not explicitly state the country of origin for the urine samples, but the study was conducted at "three intended user sites." These samples were prepared by spiking drugs into drug-free pooled urine specimens. The study itself is prospective in terms of collecting performance data from lay users.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
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Method Comparison Studies: The ground truth was established by LC/MS (Liquid Chromatography-Mass Spectrometry). This is a highly accurate analytical method, considered the gold standard for drug confirmation in urine. No human experts are explicitly mentioned for establishing the ground truth in these studies, as the LC/MS directly provides it. The "three laboratory assistants" who ran the devices are operators, not ground truth experts.
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Precision, Interference, Specificity, Effect of Urine Specific Gravity and pH, Lay-user Studies: The ground truth for these studies was established by LC/MS to confirm the drug concentrations in the spiked urine samples.
4. Adjudication Method for the Test Set
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Precision Studies: Not explicitly stated, however, the results were quantified as positive/negative based on the criteria for each concentration and then tabulated. No formal adjudication process among multiple readers is described for the precision data, as the device's output (presence/absence of line) is objectively recorded.
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Method Comparison Studies: Three "laboratory assistants" viewed the device results, and their readings were compared against the LC/MS ground truth. There is no mention of an adjudication process (e.g., 2+1, 3+1) among these three assistants. Each viewer's discordant results were individually reported.
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Lay-user Study: The results from each lay person were recorded (positive/negative) and then compared to the known LC/MS-confirmed concentration of the sample. No adjudication among lay users is mentioned.
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 Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This device is a rapid, qualitative drug test cup, which provides a direct visual result (lines appearing/not appearing). It does not involve AI assistance, nor does it involve human readers interpreting complex images or data that AI would augment. Therefore, there's no discussion of human readers improving with AI assistance.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, in the context of the device's output. The "Precision" studies and the "Interference," "Specificity," and "Effect of Urine Specific Gravity and pH" studies represent the standalone performance of the device itself to detect the analytes, as the results are based on the chemical reactions within the cup. The "Method Comparison" study also evaluates the standalone performance of the device's reading mechanism when interpreted by professional users, directly comparing it to the LC/MS reference.
7. The Type of Ground Truth Used
- The primary ground truth used across all analytical and clinical (in-house) studies was LC/MS (Liquid Chromatography-Mass Spectrometry). For the precision, interference, specificity, and pH/SG studies, the samples were spiked with known concentrations confirmed by LC/MS. For the method comparison study, unaltered clinical samples were directly compared against LC/MS results.
8. The Sample Size for the Training Set
- This device is a lateral flow immunochromatographic assay, not an AI/machine learning model. Therefore, there is no concept of a "training set" in the traditional sense for an algorithm. The development and optimization of the test's chemical components and cutoff concentrations implicitly involve internal R&D and calibration, but this is distinct from training an AI model on a dataset.
9. How the Ground Truth for the Training Set was Established
- As stated above, this is not applicable as it's not an AI/machine learning device requiring a training set. The "ground truth" for establishing the device's analytical performance (e.g., cutoff levels, cross-reactivity) would have been determined through empirical testing and comparison against established analytical methods like LC/MS during the device's development and validation.
§ 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).