(134 days)
The DRI Hydrocodone Assay is a homogeneous enzyme immunoassay for the qualitative and/or semi-quantitative determination of the presence of hydrocodone and its metabolites in human urine at a cut-off concentration of 300 ng/mL. The assay is intended to be used in laboratories and provides a simple and rapid analytical screening procedure to detect hydrocodone and its metabolites in human urine. The assay is designed for use with a number of clinical chemistry analyzers.
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/tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method
The DRI Hydrocodone assay is supplied as a liquid ready-to-use homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect Hydrocodone and Hydromorphone and Hydromorphone glucuronide. The assay is based on competition between a drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) and free drug from the urine sample, for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample, the specific antibody binds the drug labeled with G6PDH and causes a decrease in enzyme activity. This phenomenon creates a direct relationship between the drug concentration in urine and enzyme activity. The enzyme activity is determined spectrophotometrically at 340 nm by measuring the conversion of nicotinamide adenine dinucleotide (NAD) to NADH.
The assay consists of reagents (A and E).
Reagent A contains mouse monoclonal anti-Hydrocodone antibody, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as a preservative.
Reagent E: Contains Hydrocodone derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with sodium azide as a preservative.
The provided document is a 510(k) premarket notification for a medical device called the DRI Hydrocodone Assay. This device is a homogeneous enzyme immunoassay designed for the qualitative and/or semi-quantitative determination of hydrocodone and its metabolites in human urine.
Here's an analysis of the acceptance criteria and study proving the device meets those criteria, based on the provided text:
Key Takeaway: This 510(k) is for a new instrument platform (Indiko Plus) for an already cleared assay (DRI Hydrocodone Assay, K150502). Therefore, much of the study focuses on showing comparable performance between the new instrument and the previous one. The acceptance criteria are implicitly met by demonstrating performance consistent with an already legally marketed predicate device.
1. Table of Acceptance Criteria and Reported Device Performance
Since this is a 510(k) for an existing assay on a new instrument, the "acceptance criteria" are not explicitly stated as quantitative targets (e.g., "sensitivity must be >95%"). Instead, the acceptance criteria are implicitly that the performance on the new analyzer (Indiko Plus) is comparable or equivalent to the performance on the predicate analyzer (AU 680). The study aims to demonstrate that the new device performs as intended and similarly to its predicate.
| Test Category | Acceptance Criteria (Implicit) | Reported Device Performance (DRI Hydrocodone Assay on Indiko Plus) |
|---|---|---|
| Precision | Consistent and reliable results across replicates and days, reflecting expected performance relative to the cutoff. For qualitative mode, no overlap in 2SD ranges between critical concentrations (e.g., -25% and 100% of cutoff, and 100% and +25% of cutoff). | Qualitative Mode: |
- Lot #1:
- -100% to -25% of cutoff: 80/80 Negative results.
- 100% of cutoff (300 ng/mL, LC-MS/MS 318.50): 22 Negative / 58 Positive.
- +25% to +100% of cutoff: 80/80 Positive results.
- Lot #2:
- -100% to -25% of cutoff: 80/80 Negative results.
- 100% of cutoff (300 ng/mL, LC-MS/MS 318.50): 4 Negative / 76 Positive.
- +25% to +100% of cutoff: 80/80 Positive results.
Semi-quantitative Mode:
- Lot #1:
- -100% to -25% of cutoff: 80/80 Negative results.
- 100% of cutoff (300 ng/mL, LC-MS/MS 318.50): 24 Negative / 56 Positive.
- +25% to +100% of cutoff: 80/80 Positive results.
- Lot #2:
- -100% to -25% of cutoff: 80/80 Negative results.
- 100% of cutoff (300 ng/mL, LC-MS/MS 318.50): 7 Negative / 73 Positive.
- +25% to +100% of cutoff: 80/80 Positive results.
Spike Recovery: No ± 2SD overlap between 300 ng/mL samples and 225 ng/mL (all 20 replicates negative) and 375 ng/mL (all 20 replicates positive). Conclusion: Meets Acceptance Criteria. |
| Analytical Recovery and Dilution Linearity | Expected: % Recovery should be within an acceptable range (e.g., 80-120%). Dilution should demonstrate linearity. | Samples run in replicates of five in semi-quantitative mode. % Recovery ranged from 91.1% (at 1000 ng/mL) to 110.3% (at 300 ng/mL for one lot, 200 ng/mL for another). Conclusion: Meets Acceptance Criteria. |
| Method Comparison and Accuracy | High overall concordance with the confirmatory method (LC-MS/MS). Discordant samples should be explainable. | Overall concordance with LC-MS/MS: 82.4%.
- Qualitative & Semi-Quantitative Mode (combined table in document):
- True Negatives: 42
- False Positives (immunoassay positive, LC-MS/MS =300 ng/mL): 9+48 = 57
- False Negatives (immunoassay negative, LC-MS/MS =300 ng/mL): 0
Explanation for discordant samples: Cross-reactivity of immunoassay to hydromorphone and hydromorphone-3β-glucuronide. |
| Specificity (Cross-reactivity) | Known related compounds should show expected cross-reactivity. Structurally unrelated compounds should show minimal or no cross-reactivity, especially at critical concentrations. | Hydrocodone & Metabolites:
- Hydrocodone: 100% cross-reactivity at 300 ng/mL (cutoff).
- Hydromorphone: 92% cross-reactivity at 325 ng/mL.
- Hydromorphone-3β-glucuronide: 162% cross-reactivity at 185 ng/mL (higher than 100% suggests higher potency than Hydrocodone in the assay).
- Norhydrocodone: 2% at 13,000 ng/mL.
- Dihydrocodeine: 2% at 12,500 ng/mL.
Opiates & Structurally Related: Most showed
§ 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).