(173 days)
The CEDIATM Heroin Metabolite (6-AM) Assay is a homogeneous enzyme immunoassay for the in vitro qualitative and or semi-quantitative determination of the presence of heroin metabolite (6-AM) in human urine at a cut-off concentration of 10 ng/mL. The assay is intended to be used in laboratories and provides a rapid analytical screening procedure to detect 6-Acetylmorphine in human urine. The assay is designed for use with a number of clinical chemistry analyzers. This product is intended to be used by trained professionals only.
The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/ mass spectrometry (GC/MS) or Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method.
Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.
CEDIA technology uses recombinant DNA technology to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ßgalactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously re-associate to form fully active enzymes that, in the assay format, cleave a substrate. This generates a color change that can be measured spectrophotometrically.
CEDIA™ Heroin Metabolite (6-AM) Assay is supplied as a two liquid and two lyophilized reagent kit homogeneous enzyme immunoassay. The assay uses an antibody that is specific for 6-Acetylmorphine and cross reacts with Heroin. The assay has minimal cross reactivity to structurally related and unrelated compounds. In the assay, analyte in the sample competes with analyte coniugated to one inactive fragment of B-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjuqated on the inactive fragment, inhibiting the reassociation of inactive ß- galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are directly proportional to the amount of drug present in the sample.
The provided FDA 510(k) summary for the Microgenics Corporation CEDIA™ Heroin Metabolite (6-AM) Assay (K231007) does not contain the detailed information necessary to fully address all aspects of your request. This document is a summary of the device's substantial equivalence to a predicate device, not a complete study report.
Specifically, the document does not contain details regarding the study design, sample sizes for test and training sets, data provenance, expert qualifications, adjudication methods, MRMC studies, or standalone algorithm performance. The studies mentioned are focused on analytical performance characteristics (precision, spike recovery, dilution linearity, method comparison, specificity, stability) relevant to an in vitro diagnostic assay, rather than a typical AI/ML device assessment.
However, I can extract the available information regarding acceptance criteria and reported device performance:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision | Qualitative/Semi-quantitative Mode: ≥ 95% of samples below the cutoff read as negative and ≥ 95% of samples above the cutoff read as positive. | Qualitative Mode: "All 20 replicates of spiked 7.5 ng/mL and 12.5 ng/mL samples are detected as Negative and Positive, respectively, when compared to 10 ng/mL spiked sample." (This implies 100% agreement, exceeding the ≥ 95% criterion for these specific concentrations.) |
| Semi-quantitative Mode: "The spiked samples recover within 80–120% of the nominal values." | ||
| Spike Recovery | Qualitative Mode: No ± 2SD overlap between 10 ng/mL, 7.5 ng/mL, and 12.5 ng/mL samples. All 20 replicates of spiked 7.5 ng/mL and 12.5 ng/mL samples detected as Negative and Positive, respectively, compared to 10 ng/mL. | Qualitative Mode: "All 20 replicates of spiked 7.5 ng/mL and 12.5 ng/mL samples are detected as Negative and Positive, respectively, when compared to 10 ng/mL spiked sample." (Meets criteria) |
| Dilution Linearity | Linearity throughout the calibration range of 0 to 20 ng/mL with R > 0.99. Mean recovery at each level within 80-120% of expected values. | "The assay demonstrates linearity throughout the calibration range of 0 to 20 ng/mL and R > 0.99. The mean recovery at each level is within 80-120% of expected values." (Meets criteria) |
| Method Comparison | Not explicitly stated as "acceptance criteria", but implied good agreement is required. | Qualitative Mode: 100% negative agreement, 100% positive agreement, 100% overall correlation agreement. |
| Semi-quantitative Mode: 98.4% negative agreement, 98.3% positive agreement, 98.4% overall correlation agreement. | ||
| Specificity (Cross-Reactivity) | Minimal cross-reactivity with structurally related and unrelated compounds. | "The assay is specific for 6-Acetylmorphine and demonstrates cross-reactivity to heroin. Minimal cross-reactivity is observed with other structurally related and unrelated compounds." (Meets criteria) |
| Specificity (Interference) | No significant interference from endogenous and exogenous substances at tested concentrations, and within pH 3-11 and specific gravity 1.000-1.030. | "Results demonstrate that there is no significant interference from the endogenous and exogenous substances in human urine at the tested concentrations, in samples within pH range of 3-11 and in samples with specific gravity within 1.000-1.030." (Meets criteria) |
| Stability (Reagents) | Supports claim of 60 days on-board, 60 days reconstituted, and 60 days open vial. Proposed shelf-life of 24 months. | Reagent On-Board: Supports 60 days for qualitative and semi-quantitative modes. |
| Reconstituted Reagent: Supports 60 days for qualitative and semi-quantitative modes. | ||
| Open Vial: Supports 60 days for qualitative and semi-quantitative modes (data from K192943). | ||
| Real Time: Supports 24 months shelf-life (data from K192943). |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Sample Size:
- For Precision / Spike Recovery in Qualitative Mode: "All 20 replicates of spiked 7.5 ng/mL and 12.5 ng/mL samples" were used. This indicates 20 replicates for each of these two concentrations, plus presumably samples for the 10 ng/mL cutoff for comparison. The total number of individual samples is not explicitly stated beyond these replicates for specific concentrations.
- For Method Comparison: No specific number for the test set is provided, only percentages of agreement.
- For Specificity (Interference): "tested concentrations" are mentioned, but the number of samples is not provided.
- For Reagent Stability: "one lot" for on-board, reconstituted, and open vial stability, and "three lots" for real-time stability.
- Data Provenance: Not specified (e.g., country of origin, retrospective or prospective). The studies appear to be laboratory-based analytical performance studies. The "human urine" matrix is mentioned, indicating human samples were used.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This information is not provided in the document. For in vitro diagnostic devices like this assay, "ground truth" is typically established through a reference method (e.g., LC-MS/MS or GC/MS for drug levels) not by human experts interpreting images or other complex data.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not applicable/not provided. Adjudication methods like 2+1 or 3+1 are typically used in studies involving human interpretation of medical images or other subjective data where consensus among experts is needed. For an immunoassay, the "ground truth" is determined by a quantitative chemical method, not by expert consensus.
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 information is not applicable/not provided. An MRMC study is relevant for AI-powered diagnostic tools where human readers (e.g., radiologists) interact with or are assisted by the AI. This device is an in vitro diagnostic immunoassay, not an AI imaging or diagnostic algorithm designed to assist human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This information is not applicable/not provided in the context of AI algorithms. This device is an immunoassay, and its "standalone performance" is what is described in the precision, spike recovery, dilution linearity, and specificity sections. It's an automated chemical analysis, not an AI algorithm performing a task without human intervention in an AI/ML sense.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The document mentions that for confirmation, "A more specific alternative chemical method must be used...Gas chromatography/mass spectrometry (GC/MS) or Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method." This indicates that confirmatory chemical analysis (LC-MS/MS or GC/MS) serves as the "ground truth" or reference method for determining the presence and concentration of 6-Acetylmorphine in urine samples.
8. The sample size for the training set
This information is not provided. The development of an immunoassay may involve optimization and calibration with a set of samples, but these are typically not referred to as a "training set" in the context of machine learning.
9. How the ground truth for the training set was established
This information is not provided. Similar to point 8, the concept of a "training set" and its "ground truth" establishment as used in AI/ML is not directly applicable or documented for this type of in vitro diagnostic device in this summary. The development process would involve optimizing the assay's chemical components and reaction parameters using well-characterized samples.
§ 862.3650 Opiate test system.
(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).