(25 days)
The AssureTech Quick Cup Tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Secobarbital, Buprenorphine, Oxazepam, Cocaine, EDDP, Fentanyl, Ecstasy, Propoxyphene, Morphine, Methadone, Phencyclidine, Oxycodone, Norfentanyl, Methamphetamine, Nortriptyline, 6-Monoacetylmorphine, Tramadol and Marijuana in human urine at the cutoff concentrations of:
| Drug (Identifier) | Cut-off level |
|---|---|
| Amphetamine (AMP) | 500 ng/mL or 300 ng/mL |
| Secobarbital (BAR) | 300 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 150 ng/mL |
| EDDP | 300ng/ml |
| Fentanyl (FYL) | 1 ng/mL |
| Ecstasy (MDMA) | 500 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Morphine (MOR) | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | 300 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Norfentanyl (NFYL) | 5 ng/mL |
| Methamphetamine (MET) | 500 ng/mL or 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| 6-Monoacetylmorphine (6-MAM) | 10 ng/mL |
| Tramadol (TML) | 100 ng/mL |
| Marijuana (THC) | 50 ng/mL or 20 ng/mL |
Configuration of the AssureTech Quick Cup Tests can consist of any combination of the above listed drug analytes. The test may yield positive results for the prescription drugs above 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 method 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 AssureTech Multi-drug Urine Test Cup are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Secobarbital, Buprenorphine, Oxazepam, Cocaine, EDDP, Fentanyl, Ecstasy, Propoxyphene, Morphine, Methadone, Phencyclidine, Oxycodone, Norfentanyl, Methamphetamine, Nortriptyline, 6-Monoacetylmorphine, Tramadol and Marijuana in human urine at the cutoff concentrations of:
| Drug (Identifier) | Calibrator | Cut-off level |
|---|---|---|
| Amphetamine (AMP) | d-Amphetamine | 500 ng/mL or 300 ng/mL |
| Secobarbital (BAR) | Secobarbital | 300 ng/mL |
| Buprenorphine (BUP) | BUP-3-D-Glucuronide | 10 ng/mL |
| Oxazepam (BZO) | Oxazepam | 300 ng/mL |
| Cocaine (COC) | Benzoylecgonine | 150 ng/mL |
| EDDP | 2-Ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine | 300ng/ml |
| Fentanyl (FYL) | Fentanyl | 1 ng/mL |
| Ecstasy (MDMA) | 3,4-Methylenediioxy-MET | 500 ng/mL |
| Propoxyphene (PPX) | D-Propoxyphene | 300 ng/mL |
| Morphine (MOR) | Morphine | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | Methadone | 300 ng/mL |
| Phencyclidine (PCP) | Phencyclidine | 25 ng/mL |
| Oxycodone (OXY) | Oxycodone | 100 ng/mL |
| Norfentanyl (NFYL) | Norfentanyl | 5 ng/mL |
| Methamphetamine (MET) | Methamphetamine | 500 ng/mL or 300 ng/mL |
| Nortriptyline (TCA) | Nortriptyline | 1000 ng/mL |
| 6-Monoacetylmorphine (6-MAM) | 6-Monoacetylmorphine | 10 ng/mL |
| Tramadol (TML) | Cis-Tramadol | 100 ng/mL |
| Marijuana (THC) | 11-nor-9-THC-9-COOH | 50 ng/mL or 20 ng/mL |
Configuration of the AssureTech Multi-drug Urine Test Cup can consist of any combination of the above listed drug analytes. It is for in vitro diagnostic use only.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
The AssureTech Quick Cup Tests are immunochromatographic assays that use a lateral flow system for the qualitative detection of Amphetamine, Secobarbital, Buprenorphine, Oxazepam, Cocaine, EDDP, Fentanyl, Ecstasy, Propoxyphene, Morphine, Methadone, Phencyclidine, Oxycodone, Norfentanyl, Methamphetamine, Nortriptyline, 6-Monoacetylmorphine, Tramadol and Marijuana (target analytes) in human urine. The products are single-use in vitro diagnostic devices. Each test kit contains a Test Device and a package insert. Each test device is sealed with a desiccant in an aluminum pouch.
The provided FDA 510(k) Clearance Letter details the performance of the AssureTech Quick Cup Tests and AssureTech Multi-drug Urine Test Cup for qualitative and simultaneous detection of various drugs in human urine.
Here's an analysis of the acceptance criteria and the study proving the device meets those criteria:
1. Acceptance Criteria and Reported Device Performance
For in vitro diagnostic devices like these, acceptance criteria are typically related to the accuracy of the qualitative detection (positive vs. negative) compared to a gold standard, particularly around the established cutoff concentrations. The performance is assessed through analytical studies (precision, specificity, interference) and comparison studies with a confirmatory method.
Here's a table summarizing the implicit acceptance criteria based on the precision and lay-user studies, and the reported device performance. The acceptance criterion is inferred as the ideal performance for these types of tests, where results near or above the cutoff should be positive, and results significantly below should be negative. The performance data below is extracted from the "Precision" and "Lay-user study" sections.
Table of Acceptance Criteria and Reported Device Performance
| Drug (Identifier) | Cut-off Level | Implicit Acceptance Criterion (Qualitative) | Reported Performance (Precision Study - Total of 3 Lots, 50 observations per concentration) | Reported Performance (Lay-user study - Agreement %) |
|---|---|---|---|---|
| AMP300 | 300 ng/mL | -100% to -25% Cutoff: All Negative | -100%/-75%/-50%/-25% Cutoff: 100% Negative (50-/0+) | -100% to -25% Cutoff: 95%-100% agreement |
| +25% to +100% Cutoff: All Positive | +25%/+50%/%75%/+100% Cutoff: 100% Positive (50+/0-) | +25% to +75% Cutoff: 95%-100% agreement | ||
| Cutoff: Majority Positive, some Negative acceptable (reflecting assay variability) | Cutoff: 64-68% Positive (30-34+/16-20-) | Not explicitly reported for cutoff in lay-user study | ||
| MET300 | 300 ng/mL | -100% to -25% Cutoff: All Negative | -100%/-75%/-50%/-25% Cutoff: 100% Negative (50-/0+) | -100% to -25% Cutoff: 100% agreement |
| +25% to +100% Cutoff: All Positive | +25%/+50%/%75%/+100% Cutoff: 100% Positive (50+/0-) | +25% to +75% Cutoff: 95%-100% agreement | ||
| Cutoff: Majority Positive, some Negative acceptable (reflecting assay variability) | Cutoff: 66-72% Positive (33-36+/14-17-) | Not explicitly reported for cutoff in lay-user study | ||
| TML100 | 100 ng/mL | -100% to -25% Cutoff: All Negative | -100%/-75%/-50%/-25% Cutoff: 100% Negative (50-/0+) | -100% to -25% Cutoff: 100% agreement |
| +25% to +100% Cutoff: All Positive | +25%/+50%/%75%/+100% Cutoff: 100% Positive (50+/0-) | +25% to +75% Cutoff: 95% agreement | ||
| Cutoff: Majority Positive, some Negative acceptable (reflecting assay variability) | Cutoff: 64-72% Positive (32-36+/14-18-) | Not explicitly reported for cutoff in lay-user study | ||
| All other listed drugs (Configuration 1 & 2) | Various | -100% to -25% Cutoff: All Negative | Data for these drugs were reported in previous 510(k)s (K243996, K201630, K181768, K180349, K170049, K161044, K153465, K152025, K151211). The precision study for AMP300, MET300, TML100 suggests similar performance. | -100% to -25% Cutoff: 90%-100% agreement |
| +25% to +100% Cutoff: All Positive | +25% to +75% Cutoff: 90%-100% agreement |
Note: The precision study for AMP300, MET300, and TML100 used 3 lots, with "50-/0+" meaning 50 negative results and 0 positive results, and "50+/0-" meaning 50 positive results and 0 negative results. For the 'Cutoff' concentration, it shows a mix of positive and negative results, which is expected due to the nature of qualitative assays around the threshold.
2. Sample Sizes and Data Provenance
-
Precision Study:
- For AMP300, MET300, and TML100: Each drug had 8 concentrations (spanning -100% to +100% of cutoff, plus the cutoff). For each concentration, tests were performed two runs per day for 25 days, for 3 different lots.
- This means 50 observations per concentration per lot (2 runs/day * 25 days/run).
- Total observations per drug for all 3 lots: 8 concentrations * 50 observations/concentration * 3 lots = 1200 observations per drug.
- Data for other drugs refer to previous 510(k) clearances (K243996, K201630, K181768, K180349, K170049, K161044, K153465, K152025, K151211).
- Data Provenance: Retrospective, as samples were "prepared by spiking drug in negative samples" and confirmed by LC/MS. No specific country of origin is mentioned, but typically for FDA submissions, studies are conducted under GLP (Good Laboratory Practice) guidelines, often in the US or by international labs adhering to comparable standards.
- For AMP300, MET300, and TML100: Each drug had 8 concentrations (spanning -100% to +100% of cutoff, plus the cutoff). For each concentration, tests were performed two runs per day for 25 days, for 3 different lots.
-
Comparison Studies (Clinical Samples):
- For AMP300, MET300, and TML100: The tables show data broken down by "Negative" (presumably drug-free), "Low Negative" ( +50%). The sum of the positive and negative results across these categories for each operator represents the number of clinical samples tested for that drug.
- AMP300: 5 (Negative) + 15 (LN) + 19 (NCN) + 24 (NCP) + 16 (HP) = 79 samples per operator. (Operator 1)
- MET300: 4 (Negative) + 13 (LN) + 23 (NCN) + 20 (NCP) + 20 (HP) = 80 samples per operator. (Operator 1)
- TML100: 2 (Negative) + 18 (LN) + 18 (NCN) + 19 (NCP) + 20 (HP) = 77 samples per operator. (Operator 1)
- Total (approximate, as numbers vary slightly between operators): ~79+80+77 = ~236 clinical samples for AMP300, MET300, TML100 combined.
- Data for other drugs refer to previous 510(k) clearances.
- Data Provenance: Retrospective, using "unaltered clinical samples." No specific country of origin is mentioned.
- For AMP300, MET300, and TML100: The tables show data broken down by "Negative" (presumably drug-free), "Low Negative" ( +50%). The sum of the positive and negative results across these categories for each operator represents the number of clinical samples tested for that drug.
-
Lay-User Study:
- Sample Size: 280 lay persons tested the device.
- Configuration 1: 66 male + 74 female = 140 lay persons.
- Configuration 2: 87 male + 53 female = 140 lay persons.
- Data Provenance: Retrospective, samples were "prepared at the following concentrations; negative, +/-75%, +/-50%, +/-25% of the cutoff by spiking drugs into drug free-pooled urine specimens." Confirmed by LC/MS. Conducted "at three intended user sites." No specific country of origin is mentioned.
- Sample Size: 280 lay persons tested the device.
3. Number of Experts and Qualifications for Ground Truth (Clinical Samples)
- Ground Truth Establishment for Clinical Samples: LC/MS (Liquid Chromatography/Mass Spectrometry) is stated as the preferred confirmatory method and was used to confirm the concentrations of the samples. This is an objective chemical method, considered the gold standard for drug detection and quantification in urine.
- Experts: The comparison studies were performed "in-house with three laboratory assistants." While these individuals are performing the rapid tests, the ultimate ground truth is established by the LC/MS results. The "laboratory assistants" are not explicitly designated as "experts" in establishing ground truth, but rather as trained users of the device whose results are compared to the LC/MS gold standard.
4. Adjudication Method for the Test Set (Clinical Samples)
- The document states that "Operators ran unaltered clinical samples for each drug. The samples were blind labeled and compared to LC/MS results."
- There were three operators. The "Discordant Results" tables show discrepancies between the rapid test results and the LC/MS results, sometimes across multiple operators for the same sample.
- No explicit adjudication method (e.g., 2+1, 3+1) for the rapid test results themselves is described. The comparison seems to be a direct comparison of each operator's rapid test result against the LC/MS ground truth, and then discrepancies are noted. The LC/MS data serves as the final, objective ground truth.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- This document describes performance characteristics of an in-vitro diagnostic device (a qualitative urine drug test cup).
- No MRMC comparative effectiveness study was performed in the context of comparing human readers (e.g., radiologists interpreting images) with and without AI assistance. This type of study design is specific to AI/CADe (Computer-Assisted Detection) or CADx (Computer-Assisted Diagnosis) devices in imaging, which is not applicable to a lateral flow immunoassay like the AssureTech Quick Cup Tests.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
- Given this is a physical immunoassay test cup, the concept of a "standalone (algorithm only without human-in-the-loop performance)" study does not directly apply in the same way it would for a software-based AI device.
- The "Comparison Studies" with laboratory assistants and the "Lay-user study" assess the device's performance when interpreted by human users. The device itself, by producing a visual result (line/no line), is the "algorithm." Its performance is inherently tied to human interpretation of that visual output. The precision and specificity studies represent the analytical performance of the device itself.
7. Type of Ground Truth Used
- Analytical Performance Studies (Precision, Specificity, pH/SG Effect): The ground truth was established by spiking known concentrations of drugs into negative urine samples, with concentrations confirmed by LC/MS.
- Comparison Studies (Clinical Samples): The ground truth was established by LC/MS results on unaltered clinical urine samples. LC/MS is a highly accurate chemical analytical method.
- Lay-User Study: Ground truth was established by spiking known concentrations of drugs into drug-free pooled urine specimens, confirmed by LC/MS.
8. Sample Size for the Training Set
- This document describes a 510(k) submission for a traditional in-vitro diagnostic device (immunoassay). It does not mention any artificial intelligence (AI) or machine learning (ML) components that would typically require a "training set" in the computational sense.
- The terms "training set" and "test set" are common in AI/ML validation. For a traditional medical device, the studies described (precision, interference, specificity, comparison, lay-user) serve as the "validation set" against pre-defined performance criteria.
- Therefore, N/A for "training set" in the context of AI/ML.
9. How the Ground Truth for the Training Set Was Established
- N/A (as above, no "training set" in the AI/ML context).
- However, if we consider how the device itself was developed, the ground truth for optimizing its performance (e.g., antibody binding, membrane characteristics) would have relied on highly controlled experiments with known concentrations of analytes, likely confirmed by advanced analytical chemistry methods like LC/MS. This process is part of the extensive R&D and quality control that precedes a 510(k) submission.
§ 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).