(37 days)
BioSieve™ Multi-Drug Urine Test Panel tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Secobarbital, Oxazepam, Cocaine, 2- ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:
| Drug (Identifier) | Cut-off level |
|---|---|
| Amphetamine (AMP) | 1000 ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Secobarbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300 ng/mL or 150 ng/mL |
| 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) | 300 ng/mL |
| Methamphetamine (MET) | 1000 ng/mL or 500 ng/mL |
| Methylenedioxymethamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |
BioSieve™ Multi-Drug Urine Test Panel offers any combinations from 1 to 15 drugs of abuse tests but only one cutoff concentration under same drug condition will be included per device. It is for in vitro diagnostic use only. It is intended for OTC use.
The tests may yield positive results for the prescription drugs Buprenorphine, 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 applied to any drug of abuse test result, particularly in evaluating a preliminary positive result.
The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.
BioSieve™ Multi-Drug Urine Test Panel Rx tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Secobarbital, Oxazepam, Cocaine, 2-ethylidene-1.5-dimenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine at the cutoff concentrations of:
| Drug | Calibrator | Cut-off (ng/mL) |
|---|---|---|
| Amphetamine (AMP) | D-Amphetamine | 1,000 or 500 |
| Barbiturates (BAR) | Secobarbital | 300 |
| Buprenorphine (BUP) | Buprenorphine | 10 |
| Oxazepam (BZO) | Oxazepam | 300 |
| Cocaine (COC) | Benzoylecgonine | 300 or 150 |
| 2-ethylidene-1,5-dimethyl-3,3- | ||
| diphenylpyrrolidine (EDDP) | 2-ethylidene-1,5-dimethyl-3,3- | |
| diphenylpyrrolidine | 300 | |
| Ecstasy (MDMA) | D,L- Methylenedioxy-methamphetamine | 500 |
| Methamphetamine (MET) | D-Methamphetamine | 1,000 or 500 |
| Morphine (MOP/OPI) | Morphine | 2,000 or 300 |
| Methadone (MTD) | Methadone | 300 |
| Oxycodone (OXY) | Oxycodone | 100 |
| Phencyclidine (PCP) | Phencyclidine | 25 |
| Propoxyphene (PPX) | Propoxyphene | 300 |
| Nortriptyline (TCA) | Nortriptyline | 1,000 |
| Marijuana (THC) | 11-nor-Δ9-THC-9 COOH | 50 |
BioSieve™ Multi-Drug Urine Test Panel Rx offers any combinations from 1 to 15 drugs of abuse tests but only one cutoff concentration under same drug condition will be included per device. It is for in vitro diagnostic use only. It is intended for prescription use.
The tests may yield positive results for the prescription drugs Buprenorphine, 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 applied to any drug of abuse test result, particularly in evaluating a preliminary positive result.
The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.
The BioSieve™ Multi-Drug Urine Test Panel and BioSieve™ Multi-Drug Urine Test Panel Rx are rapid, single-use in vitro diagnostic devices. Each test kit contains a test device in one pouch. One pouch contains a test BioSieve™ Panel and two desiccants, and a package insert. The BioSieve™ Multi-Drug Urine Test Panel is intended for over-the-counter use and the BioSieve™ Multi-Drug Urine Test Panel Rx is intended for prescription use.
Acceptance Criteria and Device Performance for BioSieve™ Multi-Drug Urine Test Panel
This document describes the acceptance criteria and the studies performed to demonstrate that the BioSieve™ Multi-Drug Urine Test Panel meets these criteria.
1. Acceptance Criteria and Reported Device Performance
The core acceptance criterion for the BioSieve™ Multi-Drug Urine Test Panel, as derived from the provided precision studies, is the accurate qualitative detection of drugs at various concentrations relative to the defined cutoff level. Specifically, the device is expected to:
- Consistently report Negative (no drug detected) for samples with drug concentrations at or below -25% of the cutoff level (e.g., -100% cutoff, -75% cutoff, -50% cutoff, -25% cutoff).
- Consistently report Positive (drug detected) for samples with drug concentrations at or above +25% of the cutoff level (e.g., +25% cutoff, +50% cutoff, +75% cutoff, +100% cutoff).
- Demonstrate a balanced distribution of Positive and Negative results around the cutoff level (e.g., approximately 50% positive and 50% negative).
The reported device performance, based on the precision studies for each drug, generally aligns with these criteria. For concentrations at or below -25% of the cutoff, almost all results were negative (e.g., 50-/0+ indicating 50 negative and 0 positive). For concentrations at or above +25% of the cutoff, almost all results were positive (e.g., 0-/50+ indicating 0 negative and 50 positive). At the cutoff concentration, the results showed a mix of positive and negative, reflecting the expected performance of a qualitative assay near its detection threshold (e.g., 23-/27+, 26-/24+, etc.).
Table of Acceptance Criteria and Reported Device Performance (Example for BUP 10, PCP 25, THC 50, OXY 100)
| Concentration by LC/MS (relative to cutoff) | Acceptance Criteria for Qualitative Result | Reported Performance (Example: BUP 10) | Reported Performance (Example: PCP 25) | Reported Performance (Example: THC 50) | Reported Performance (Example: OXY 100) |
|---|---|---|---|---|---|
| -100% cutoff | Negative | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ |
| -75% cutoff | Negative | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ |
| -50% cutoff | Negative | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ |
| -25% cutoff | Negative | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ |
| Cutoff | Mixed (approx. 50% Pos / 50% Neg) | 26-/24+ (Avg. across lots) | 24-/26+ (Avg. across lots) | 26-/24+ (Avg. across lots) | 25-/25+ (Avg. across lots) |
| +25% cutoff | Positive | 0-/50+ | 0-/50+ | 0-/50+ | 0-/50+ |
| +50% cutoff | Positive | 0-/50+ | 0-/50+ | 0-/50+ | 0-/50+ |
| +75% cutoff | Positive | 0-/50+ | 0-/50+ | 0-/50+ | 0-/50+ |
| +100% cutoff | Positive | 0-/50+ | 0-/50+ | 0-/50+ | 0-/50+ |
Note: The table above provides a representative sample. The full document lists extensive data for each drug, demonstrating similar performance.
2. Sample Sizes Used for the Test Set and Data Provenance
The primary analytical performance test (Precision Study) used a substantial sample size. For each drug, tests were performed over 25 days, with two runs per day, using three different lots of test panels. This means for each concentration level tested per drug (e.g., -100% cutoff, -50% cutoff, cutoff, +50% cutoff, +100% cutoff), there were 25 days * 2 runs * 3 lots = 150 individual tests.
The method comparison studies utilized 80 unaltered urine samples for each drug, divided into 40 negative and 40 positive. These samples were run by three different operators.
The lay-user study included a total of 280 participants.
- Configuration 1: 64 males and 76 females (140 participants)
- Configuration 2: 67 males and 73 females (140 participants)
For each drug and each concentration level in the lay-user study, there were 20 test results. Given there are 7 concentration levels per drug, this amounts to 140 results per drug per configuration.
Data Provenance: The document does not explicitly state the country of origin for the data. However, the studies were performed by VivaChek Biotech (Hangzhou) Co., Ltd. located in Hangzhou, China, suggesting the data was collected there. The studies appear to be retrospective as they involve prepared samples or collected unaltered urine samples that were then tested.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for the analytical performance and method comparison studies was established using LC/MS (Liquid Chromatography/Mass Spectrometry) or LC/MS/MS. LC/MS is a highly accurate and widely accepted gold-standard analytical method for confirming drug concentrations in urine.
The document does not specify the "number of experts" or their "qualifications" in the context of establishing LC/MS ground truth, as LC/MS is an instrumental method that provides objective quantitative results. The operation and interpretation of LC/MS data typically rely on trained laboratory personnel with expertise in analytical chemistry, but their specific "qualifications" (e.g., years of experience) are not detailed in this submission.
For the lay-user study, the ground truth was also established by spiking known concentrations of drugs into drug-free urine, confirming these concentrations via LC/MS or LC/MS/MS.
4. Adjudication Method for the Test Set
For the analytical performance (precision) studies, the raw results for each concentration level are presented (e.g., 26-/24+). This implies no specific "adjudication method" beyond the direct comparison of the device's qualitative result (positive/negative) against the quantitative LC/MS ground truth. The acceptance criteria for the cutoff concentration already imply a mixed outcome is expected.
For the method comparison study, discordant results are explicitly listed with the LC/MS result compared against the device's result by each operator. This indicates a direct comparison to the LC/MS ground truth rather than an adjudication process between device results.
For the lay-user study, the "agreement (%)" is calculated based on how often the lay user's interpretation of the device result matched the expected result based on the spiked concentration (and confirmed by LC/MS). Again, this is a direct comparison to established ground truth, not an adjudication of human interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done in the traditional sense of comparing human readers with and without AI assistance, as this device (BioSieve™ Multi-Drug Urine Test Panel) is a lateral flow immunochromatographic assay, not an AI-powered diagnostic tool for image or data interpretation.
The studies involve:
- Analytical performance: Device-to-LC/MS comparison.
- Method comparison: Three operators reading the device and comparing to LC/MS. This is a multi-reader study, but comparing the device's output to a gold standard, not assessing the improvement of human readers with AI assistance.
- Lay-user study: Multiple lay users interpreting the device results based on provided instructions. This evaluates the ease of use and interpretability for the intended over-the-counter audience, not the effectiveness of AI assistance.
Therefore, an "effect size of how much human readers improve with AI vs without AI assistance" is not applicable to this device or the studies presented.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Given that the BioSieve™ Multi-Drug Urine Test Panel is a physical, lateral flow immunochromatographic assay, it inherently requires a human-in-the-loop to visually interpret the test lines. It is not an "algorithm only" device. Therefore, a standalone (algorithm only) performance study was not done and is not applicable. The precision, comparison, and lay-user studies all involve human observation and interpretation of the visual reaction.
7. The Type of Ground Truth Used
The primary type of ground truth used across all analytical studies (precision, specificity, interference, method comparison, and lay-user studies) is analytical confirmation by LC/MS (Liquid Chromatography/Mass Spectrometry) or LC/MS/MS. This a quantitative chemical method considered a gold standard for drug detection and concentration measurement.
For the precision studies, various concentrations of each drug were "spiking target drug in drug-free urine samples" and "confirmed by LC/MS."
For the method comparison studies, "unaltered urine samples were blind labeled and compared to LC/MS results."
For the lay-user study, samples were "spiked with drug(s) into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/MS or LC/MS."
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. This device is a biochemical immunoassay, not an AI/ML-based diagnostic. Therefore, there is no separate "training set" as understood in a computational context.
The studies described are for verification and validation of the device's analytical performance.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" for an AI/ML algorithm for this device, this question is not applicable. The chemical and biological principles of the immunoassay define its detection capabilities, rather than a learned model from a training set.
§ 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).