(28 days)
Healgen COC One Step Cocaine Test is an immunochromatographic assay for the qualitative determination of Benzoylecgonine in human urine at a Cut-Off concentration of 300 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.
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 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.
For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.
Healgen MOP One Step Morphine Test is an immunochromatographic assay for the qualitative determination of morphine in human urine at a Cut-Off concentration of 300 ng/mL. The test is available in a Strip format, a Cassette format, a Dip Card format and a Cup format.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GO/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.
For in vitro diagnostic use only. It is intended for over-the-counter and for prescription use.
Healgen COC One Step Cocaine Test and Healgen MOP One Step Morphine Test are immunochromatographic assays for Cocaine and Morphine. Each assay test is a lateral flow, one step system for the qualitative detection of Benzoylecgonine and Morphine (target analyte) in human urine. The product is a single-use in vitro diagnostic device, which comes in the form of: Strips, Cassettes, DipCards, or Cups. It contains a Test Device (in one of the four formats), a package insert and a urine cup. Each test device is sealed with a desiccant in an aluminum pouch.
The sponsor, HEALGEN SCIENTIFIC LLC, submitted a 510(k) premarket notification (K141647) for the Healgen COC One Step Cocaine Test and Healgen MOP One Step Morphine Test. Both devices are immunochromatographic assays intended for the qualitative determination of Benzoylecgonine and Morphine, respectively, in human urine at a cut-off concentration of 300 ng/mL. They are available in Strip, Cassette, Dip Card, and Cup formats for in vitro diagnostic use, intended for both over-the-counter and prescription use. The predicate device is the K052115 First Check Multi Drug Cup 12.
1. Table of Acceptance Criteria and Reported Device Performance:
The document does not explicitly state acceptance criteria in terms of specific performance metrics (e.g., minimum sensitivity or specificity percentages to be achieved). However, the performance characteristics studies (precision, cut-off, interference, specificity, and method comparison) are presented to demonstrate the device's acceptable performance and substantial equivalence to the predicate. The "acceptance criteria" can be inferred from the positive results observed in these studies, particularly the concordance with GC/MS and the high percentage of correct results from lay users around the cut-off.
Healgen COC One Step Cocaine Test Performance (Summary from provided data):
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision | Consistent results across lots and runs for samples at specified concentrations relative to cut-off. | Cocaine (COC) Strip, Cassette, Dip Card, Cup Formats: |
| -100% to -25% Cut-off: 100% negative results (e.g., 50-/0+ for 3 lots, 2 runs/day for 25 days, totaling 150 tests/lot) | ||
| +25% to +100% Cut-off: 100% positive results (e.g., 50+/0- for 3 lots, 2 runs/day for 25 days, totaling 150 tests/lot) | ||
| Cut-off: Mixed results, indicating sensitivity around the cut-off (e.g., Strip: 18-/32+, Cassette: 22-/28+, Dip Card: 20-/30+, Cup: 18-/32+ for 3 lots). | ||
| Cut-off | Correctly identify positive/negative at and around the cut-off (300 ng/mL). | All samples at or above +25% cut-off (e.g., 375 ng/mL) were positive. All samples at or below -25% cut-off (e.g., 225 ng/mL) were negative. |
| Interference | No significant interference from common substances found in urine. | Numerous compounds (e.g., 4-Acetamidophenol, Aspirin, Ibuprofen, Methadone, etc.) at 100 µg/mL showed no interference in drug-free urine or urine spiked at 25% above cut-off levels. |
| Specificity (Cross-reactivity) | Limited cross-reactivity to ensure accurate detection of the target analyte. | Cocaethylene: 100% cross-reactivity (positive at 300 ng/mL). |
| Cocaine HCl: 100% cross-reactivity (positive at 300 ng/mL). | ||
| Effect of Urine Specific Gravity and pH | Consistent results across a range of urine specific gravity and pH. | Results were all positive for samples at and above +25% cut-off and all negative for samples at and below -25% cut-off, across specific gravity 1.000-1.035 and pH 4-9. |
| Method Comparison (Clinical Samples) | High concordance with GC/MS results, especially for samples further from the cut-off. | COC Strip Format: Out of 80 clinical samples (40 negative, 40 positive), for Viewer A: 0 false positives, 1 false negative (GC/MS 303 ng/mL, device negative) |
| COC Cassette Format: For Viewer B: 0 false positives, 0 false negatives. | ||
| Similar high concordance across all formats and viewers, with a few discordant results near the cut-off (e.g., 303 ng/mL or 305 ng/mL GC/MS concentrations read as negative by the device). | ||
| Lay-User Study | High percentage of correct results by lay users, demonstrating ease of use and interpretability. | COC Strip: 90% correct at -25% Cut-off, 95% correct at +25% Cut-off, 100% at other concentrations. Overall high accuracy. Users indicated instructions were easily followed (Flesch-Kincaid Grade Level 7). |
Healgen MOP One Step Morphine Test Performance (Summary from provided data):
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Precision | Consistent results across lots and runs for samples at specified concentrations relative to cut-off. | Morphine (MOP) Strip, Cassette, Dip Card, Cup Formats: |
| -100% to -25% Cut-off: 100% negative results (e.g., 50-/0+ for 3 lots, 2 runs/day for 25 days, totaling 150 tests/lot) | ||
| +25% to +100% Cut-off: 100% positive results (e.g., 50+/0- for 3 lots, 2 runs/day for 25 days, totaling 150 tests/lot) | ||
| Cut-off: Mixed results, indicating sensitivity around the cut-off (e.g., Strip: 16-/34+, Cassette: 18-/32+, Dip Card: 22-/28+, Cup: 20-/30+ for 3 lots). | ||
| Cut-off | Correctly identify positive/negative at and around the cut-off (300 ng/mL). | All samples at or above +25% cut-off (e.g., 375 ng/mL) were positive. All samples at or below -25% cut-off (e.g., 225 ng/mL) were negative. |
| Interference | No significant interference from common substances found in urine. | Numerous compounds (e.g., Acebutolol, Aspirin, Ibuprofen, Cocaine hydrochloride, etc.) at 100 µg/mL showed no interference in drug-free urine or urine spiked at 25% above cut-off levels. |
| Specificity (Cross-reactivity) | Limited cross-reactivity to ensure accurate detection of the target analyte. | 6-Acetylmorphine: 75% cross-reactivity (positive at 400 ng/mL). |
| Codeine: 100% cross-reactivity (positive at 300 ng/mL). | ||
| Various other opiate-related compounds showed varying degrees of cross-reactivity (e.g., Heroin 50%, Hydromorphone 10%). | ||
| Effect of Urine Specific Gravity and pH | Consistent results across a range of urine specific gravity and pH. | Results were all positive for samples at and above +25% cut-off and all negative for samples at and below -25% cut-off, across specific gravity 1.000-1.035 and pH 4-9. |
| Method Comparison (Clinical Samples) | High concordance with GC/MS results, especially for samples further from the cut-off. | MOP Strip Format: Out of 80 clinical samples (40 negative, 40 positive), for Viewer A: 0 false positives, 1 false negative (GC/MS 307 ng/mL, device negative). Viewer B showed one false positive (GC/MS 298 ng/mL) and one false negative (GC/MS 328 ng/mL). |
| Similar high concordance across all formats and viewers, with a few discordant results near the cut-off. | ||
| Lay-User Study | High percentage of correct results by lay users, demonstrating ease of use and interpretability. | MOP Strip: 90% correct at -25% Cut-off, 95% correct at +25% Cut-off, 100% at other concentrations. Overall high accuracy. Users indicated instructions were easily followed. |
2. Sample Size Used for the Test Set and Data Provenance:
-
Precision Study Test Set: For each drug (Cocaine and Morphine) and each format, 3 lots were tested. For each lot, 9 concentration levels were tested. For each concentration, tests were performed two runs per day for 25 days.
- This implies 3 lots * 9 concentrations * (2 runs/day * 25 days/run) = 3 * 9 * 50 = 1350 tests per lot per concentration type (e.g., Cocaine Strip).
- The results are reported as "X-/Y+" (Negative/Positive) out of 50 total readings per lot, meaning 50 tests were performed per lot per concentration level. So, 3 lots * 9 concentrations * 50 tests/concentration = 1350 tests were conducted for each device format (Strip, Cassette, Dip Card, Cup) for both Cocaine and Morphine.
- Data Provenance: The samples were "prepared by spiking drug in negative samples." The document does not specify the country of origin, but it implies a controlled laboratory setting (in-house) rather than collected human samples for this specific study. It is retrospective in the sense that the concentrations were known and confirmed by GC/MS beforehand.
-
Cut-off Verification Test Set: A total of 150 samples (equally distributed at -50%, -25%, cut-off, +25%, +50% cut-off concentrations) were tested. These were tested using three different lots of each device by three different operators.
- Data Provenance: Samples were "spiking drug in negative samples." No country of origin is mentioned, likely in-house.
-
Interference and Specificity Test Set: No specific sample size is given beyond "three batches of each device for all formats." The concentrations of interfering substances or cross-reactants were tested against drug-free urine and urine spiked at 25% above cut-off levels.
- Data Provenance: Not specified, likely in-house laboratory.
-
Method Comparison Studies (Clinical Samples Test Set): 80 unaltered clinical samples were used for each target drug (Cocaine and Morphine) and each device format (Strip, Cassette, Dip Card, Cup). Specifically, these were 40 negative and 40 positive samples.
- Data Provenance: "unaltered clinical samples". Country of origin is not specified, but the study was performed "in-house." These were retrospective/archived samples as their GC/MS results were already known and they were blind-labeled.
-
Lay-User Study Test Set: 140 lay persons tested the cocaine devices, and another 140 lay persons tested the morphine devices. Each participant was provided with 1 blind-labeled sample. For each drug, urine samples were prepared at 7 concentration levels (negative, +/-75%, +/-50%, +/-25% of the cutoff). The tables show 20 samples per concentration level, totaling 7 * 20 = 140 samples per drug group which corresponds to the number of lay users.
- Data Provenance: Urine samples were prepared by "spiking drugs into drug free-pooled urine specimens." Country of origin is not specified. The study involved human participants, making it a prospective study in terms of user interaction, but the samples themselves were prepared in a controlled manner.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- Precision, Cut-off, Interference, Specificity, Lay-User Studies: The ground truth for these studies was established by GC/MS confirmation of the spiked drug concentrations in the urine samples. GC/MS (Gas Chromatography/Mass Spectrometry) is a highly accurate and accepted method for drug confirmation. No human experts are explicitly mentioned for establishing ground truth as GC/MS is the gold standard.
- Method Comparison Studies (Clinical Samples): The ground truth was established by GC/MS results. The study states: "compared to GC/MS results." Again, no human experts are explicitly mentioned for interpreting these GC/MS results as they are quantitative and serve as the definitive ground truth for drug concentration.
4. Adjudication Method for the Test Set:
- Precision, Cut-off, Interference, Specificity Studies: No explicit adjudication method is mentioned beyond the initial GC/MS confirmation of sample concentrations. The device results were presumably compared directly to these known concentrations.
- Method Comparison Studies (Clinical Samples): Three "laboratory assistants" (referred to as Viewer A, Viewer B, Viewer C) independently interpreted the results of the rapid tests. The discordant results (where the rapid test device result did not match the GC/MS ground truth) are listed individually for each viewer and sample. This indicates that while there were multiple readers (viewers), their results were not adjudicated against each other to form a consensus before comparison to GC/MS. Instead, individual performance against GC/MS was reported.
- Lay-User Study: Results from individual lay persons were compared against the GC/MS confirmed concentrations of the samples they tested. No adjudication between lay readers is mentioned; each reader's accuracy was assessed independently.
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:
This device is an immunochromatographic assay for drug detection in urine, which is a rapid, visually-read test. It does not utilize AI. Therefore, an MRMC comparative effectiveness study involving AI assistance for human readers was not performed and is not applicable to this type of device. The studies involved human readers (laboratory assistants and lay users) interpreting the results of a non-AI-powered device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
Not applicable. This device is a manual, visually-read immunochromatographic test. There is no algorithm component to perform standalone testing. The performance characteristics represent the device's inherent analytical capabilities when used as intended.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.):
The primary ground truth used for all performance studies (precision, cut-off, interference, specificity, and method comparison) was GC/MS (Gas Chromatography/Mass Spectrometry). This is considered a highly accurate and quantitative analytical method, serving as an objective gold standard for drug concentration in urine. For the lay-user study, the ground truth was also GC/MS confirmed drug concentrations in the prepared samples.
8. The Sample Size for the Training Set:
This is a rapid diagnostic test, not a machine learning or AI-based device, so the concept of a "training set" in the context of algorithm development is not applicable. The device's formulation and manufacturing processes are likely developed through R&D and optimization, not through training on a dataset in the AI sense.
9. How the Ground Truth for the Training Set Was Established:
As there is no "training set" in the context of an AI/ML algorithm for this device, this question is not applicable.
§ 862.3250 Cocaine and cocaine metabolite test system.
(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite 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).