(14 days)
The Chemtron Biotech, Inc.'s Chemtrue® Single/Multi-Panel Drug Screen Cassette and Dip Card Tests are rapid lateral flow immunoassays for the qualitative detection of up to six of the following drugs in a variety of combinations in human urine. The designed cutoff concentrations and the calibrators used for these drugs are as follows:
Analyte Abbreviation Calibrator Cutoff Concentration
Amphetamine AMP d-Amphetamine 1000 ng/mL
Cocaine COC Benzoylecgonine 300 ng/mL
Marijuana THC 11-nor-Δ9-THC9-COOH 50 ng/mL
Methamphetamine MET d-Methamphetamine 1000 ng/mL
Opiates OPI/MOR Morphine 300 ng/mL
Phencyclidine PCP Phencyclidine 25 ng/mL
The Chemtrue® Single/Multi-Panel Drug Screen Cassette and Dip Card Tests are intended for the qualitative detection of drugs of abuse for health care professional, in vitro diagnostic and Over-the-Counter (OTC) use. These assays provide only a preliminary result. A more specific alternative chemical method must be used in order to obtain a confirmed assay result. Gas Chromatography / Mass Spectrometry (GC/MS) or Liquid Chromatography / Mass Spectrometry (LC/MS) are the preferred confirmatory methods.
Clinical consideration and professional judgment should be applied to any drugs of abuse test result, particularly when preliminary positive results are indicated.
The Drugs of Abuse (DOA) Screen Panels are one-step lateral flow immunoassays in which chemically labeled drugs (drug-protein conjugates) compete for limited antibody binding sites with drugs that may be present in urine. The test device consists of up to six test strips placed into separate panels of a plastic holder. On each test strip, a drug-protein conjugate is striped on the test band of the membrane - known as the test region (T) and the drug antibody-colloidal gold conjugate pads are placed at one end of the membrane (opposite in morphine). In the absence of drugs in the urine, the solution of the colored antibody-colloidal gold conjugates move along with the sample solution upward chromatographically by capillary action across the immobilized drug-protein conjugate zones on the test band region. The colored antibody-gold conjugates then complexes with the drug-protein conjugates to form visible lines. Therefore, the formation of the visible precipitant in the test band occurs when the test urine is negative for the drug. If any drug is present in the urine, the drug/metabolite antigen competes with drug-protein conjugates on the test band region for the limited antibody on the colored drug antibody-collooidal gold conjugate pad. When a sufficient amount of drug is present in the urine, the drug will saturate the limited antibody binding sites and the colored antibody -colloidal gold conjugate cannot bind to the drug-protein conjugate at the test region of the test strip. Therefore, absence of the color band on the test region indicates a preliminary positive result.
A control band with a different antibody reaction is added to the membrane strip at the control region (C) to indicate that the test has performed properly. This control line is manufactured as a builtin internal control of the test device and should always appear regardless of the presence of drug or metabolite. If the control line does not appear the test cassette should be discarded. The presence of this colored band in the control region also serves 1) as verification that adequate specimen volume is added (flooding, if too much urine is added, or no flow, due to insufficient urine volume), 2) the test device IS properly functioning, and 3) as reagent control.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
The core acceptance criteria for this device are its accuracy of detection for various drugs of abuse when compared to a confirmatory method (GC/MS). The study aimed to demonstrate that lay-users could perform the testing and interpret the results correctly with a high level of agreement.
Table 1: Acceptance Criteria and Reported Device Performance (Summary from provided text)
| Analyte | Cutoff Concentration | Acceptance Criteria (Implied) | Reported Performance (Agreement with GC/MS) |
|---|---|---|---|
| Amphetamine | 1000 ng/mL | High agreement (e.g., >95%) | 98.9% (Dip Card), 100% (Cassette) |
| Cocaine | 300 ng/mL | High agreement (e.g., >95%) | 100% (Dip Card), 100% (Cassette) |
| Marijuana (THC) | 50 ng/mL | High agreement (e.g., >95%) | 100% (Dip Card), 100% (Cassette) |
| Methamphetamine | 1000 ng/mL | High agreement (e.g., >95%) | 100% (Dip Card), 100% (Cassette) |
| Opiates (Morphine) | 300 ng/mL | High agreement (e.g., >95%) | 100% (Dip Card), 98.9% (Cassette) |
| Phencyclidine | 25 ng/mL | High agreement (e.g., >95%) | 98.9% (Dip Card), 98.9% (Cassette) |
| Overall | - | >98.9% total correlation | 98.9% total correlation |
Note: The document explicitly states "Correlation studies produced a 98.9% total correlation when compared to the GC/MS methodology" as the overarching performance metric, suggesting this was the primary acceptance criterion. The individual agreement percentages for each drug further support the overall claim.
Study Details
-
Sample size used for the test set and the data provenance:
- Sample Size: The study evaluated 200 OTC (Over-the-Counter) lay-users. The tables provided show results for various drug concentrations, including "no drug present", "GC/MS Negative (-50% to -25% cutoff)", "Near cutoff negative (-25% cutoff to cutoff)", "Near cutoff positive (cutoff to +25% cutoff)", "GC/MS Positive (+25% to +50% cutoff)", and "GC/MS Positive (+50% to 200% cutoff)". For each of these categories and for each drug, there were typically 30 samples, indicating a total of 180 samples per drug, and thus 1080 samples across all 6 drugs for each device type (Dip Card and Cassette). The document states "blind-labeled spiked urine correlation study," implying the urine samples were prepared and then tested.
- Data Provenance: The study used "spiked urine" samples, meaning the drug concentrations were artificially introduced into urine. The samples were tested by lay-users from "three (3) sites". It's not explicitly stated if these sites were in a specific country, but given the company's address (San Diego, CA, USA) and the FDA submission, it's highly probable the study was conducted in the USA. The study design is prospective in the sense that new tests were run according to a predefined protocol.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of experts: Not applicable in the traditional sense of human expert consensus. The ground truth was established by a laboratory method.
- Qualifications: The gold standard for establishing ground truth was Gas Chromatography / Mass Spectrometry (GC/MS) methodology. This is a highly accurate analytical chemistry technique performed by trained laboratory personnel.
-
Adjudication method for the test set:
- Adjudication: Not applicable. The ground truth was determined by GC/MS, so there was no need for human expert adjudication to resolve discrepancies in ground truth. The study compared the device's reading to the GC/MS result directly.
-
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:
- MRMC Study: No, an MRMC comparative effectiveness study was not performed in the context of human readers improving with or without AI assistance. This device is a rapid, visually-read immunoassay, not an AI-powered diagnostic tool requiring interpretation by experts in an MRMC setting. The study assessed the ability of "200 OTC lay-users" to correctly interpret the visual results of the device.
-
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Standalone Performance: No, a standalone algorithm-only performance was not done. The device is a "visually-read" immunoassay where human users (specifically "lay-users" for OTC use) interpret the presence or absence of colored lines. The reported performance includes the human interpretation component.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Type of Ground Truth: The ground truth was established using an analytical reference method: Gas Chromatography / Mass Spectrometry (GC/MS). This is a highly accurate chemical method for identifying and quantifying substances in a sample. The document also mentions Liquid Chromatography / Mass Spectrometry (LC/MS) as an alternative confirmatory method.
-
The sample size for the training set:
- Training Set Sample Size: The document does not explicitly state a training set size. For this type of immunoassay device, there isn't typically a "training set" in the machine learning sense. The device's performance characteristics (e.g., analytical sensitivity, precision, specificity, stability) were established and likely optimized during product development, but this process isn't described as using a distinct "training set" in the filing. The "K102203" submission is referenced for "Other performance data" such as analytical sensitivity and precision, which would have been part of the internal development and validation, not a separate training set as understood in AI/ML.
-
How the ground truth for the training set was established:
- Training Set Ground Truth: As there's no explicitly defined "training set" in the context of this immunoassay's submission, the method for establishing its ground truth is not detailed via this document. However, the foundational analytical sensitivity and specificity of immunoassays are typically established by running known concentrations of analytes and interferents and confirming these with reference methods like GC/MS or LC/MS during the assay's development and internal 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).