(222 days)
The Psychemedics Microplate EIA For Cotinine in Hair is an in vitro diagnostic device for the qualitative detection of cotinine in human head and body hair as an aid in the detection of cotinine after use or exposure to tobacco products. The assay is intended for a single site and uses a cutoff calibrator of 200 pg cotinine/mg hair. This device is intended exclusively for Psychemedics use only and is not intended for sale to anyone.
The Psychemedics Microplate EIA For Cotinine in Hair provides only a preliminary analytical test result. A more specific alternate chemical method must be used to obtain a confirmed analytical result. Liquid Chromatography/Mass spectrometry/Mass spectrometry (LC/MS/MS) is the confirmatory method used by Psychemedics Corporation. The LC/ MS/MS analysis uses a cutoff, after extensive washing of 100 pg cotinine/mg hair with presence of hydroxycotinine at or above 10 pg/mg hair.
The Psychemedics Microplate EIA For Cotinine in Hair consists of two parts; a pre-analytical hair treatment procedure (to convert the solid matrix of hair to a measurable liquid matrix) and the screening assay, the Psychemedics Microplate EIA for Cotinine. The screening portion of the test system consists of (1) microplate wells coated with cotinine conjugated to bovine serum albumin (BSA), polyclonal rabbit anti-cotinine, goat antirabbit secondary antibody conjugated to HRP (horseradish peroxidase), substrate [3, 3', 5, 5' tetramethylbenzidine (TMB)], HCl to acidify (and stop the reaction), and wash buffer for washing the plates. Absorbance in the wells is read with a microplate reader.
Liquid Chromatography/Mass spectrometry/Mass spectrometry (LC/MS/MS) is the confirmatory method used by Psychemedics Corporation. The LC/MS/MS analysis uses a cutoff, after extensive washing of the hair, of 100 pg cotinine/mg hair with presence of hydroxycotinine at or above 10 pg/mg hair.
Here's a structured summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance for Psychemedics Microplate EIA for Cotinine in Hair (K192517)
1. Table of Acceptance Criteria and Reported Device Performance:
The document primarily focuses on demonstrating substantial equivalence to a predicate device and provides performance data rather than explicitly stating pre-defined "acceptance criteria" as pass/fail thresholds for specific metrics. However, based on the performance testing results, we can infer the implied acceptance criteria.
| Performance Metric | Implied Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| Sensitivity (EIA) | No false negatives above the LC/MS/MS confirmation cutoff relative to the 200 pg/mg hair EIA cutoff. | No samples that screened negative were false negatives (i.e., no negative EIA result confirmed above 200 pg cotinine/mg hair by LC/MS/MS). |
| Specificity (EIA) | Minimal cross-reactivity with related compounds; no interference from common substances. | Specific cross-reactivity percentages documented (e.g., 50% for trans-3-hydroxycotinine, 0.4% for nicotine); 86 compounds showed no cross-reactivity/interference. |
| Precision (EIA) - Qualitative | Able to consistently classify samples at and around the cutoff (200 pg/mg hair) as negative or positive. | Intra-Assay: 10/10 samples correctly classified for all levels (-100% to +100% of cutoff, except -25% level where 10/10 classified as negative). |
| Inter-Assay: 50/50 samples correctly classified for all levels (-100% to +100% of cutoff, except -25% level where 50/50 classified as negative). | ||
| Precision (LC/MS/MS) - Intra-Assay (around cutoff) | %CV 0.995; actual data points deviate 0.995. Average value of 5 determinations within 15% of predicted Y value. Actual data points deviated 90% from hair; Recovery > 65% for cotinine and > 55% for hydroxycotinine with SPE. | Recovery from hair was > 91.6%; Recoveries of analytes and I.S. with SPE were > 65% for cotinine and > 55% for hydroxycotinine. |
| Carryover (LC/MS/MS) | No signal detected in negative sample following a high positive sample (up to 1000 pg/mg hair). | No signal detected in negative sample after 1000 pg/mg sample. |
| LLOQ/LOD Precision (LC/MS/MS) | S:N ratio > 19:1 to 20:1. Results within 15% of target for LLOQ/LOD spiked samples. | S:N ratios 161-302 for cotinine, 137-217 for hydroxycotinine (at 10 pg/mg hair). Results showed 109.5% and 110.9% of target, respectively. |
| Cosmetic Treatments | Negative samples remain negative; positive samples remain positive. | All negative samples remained negative; all positive samples remained positive. |
| Environmental Contamination | Confirmed positive samples (from contamination) should drop below LC/MS/MS cutoff after washing procedure. | Heavily smoke-exposed hair, after extensive washing, resulted in no samples above the LC/MS/MS cutoff of 100 pg cotinine/mg hair. |
2. Sample Size Used for the Test Set and Data Provenance:
- Comparison Study (EIA vs. LC/MS/MS): A total of 82 samples were utilized.
- Data Provenance: The document states "Samples were identified for inclusion in the study by screening with a screening assay for cotinine in serum (K974234)." It doesn't explicitly state the country of origin or if they were retrospectively or prospectively collected human hair samples, but implies they are human hair samples.
- Precision Studies (EIA): Not explicitly stated as "test set," but 10 samples were used for intra-assay and 50 samples for inter-assay precision at various levels around the cutoff. These were "negative hair spiked with previously LC/MS/MS-validated calibrator and control spiking solutions."
- Cosmetic Treatments: Sets of 5 cotinine-negative and 6 cotinine-positive samples (total of 11) were used.
- Environmental Contamination: 7 hair samples were exposed to smoke for this specific test.
- LC/MS/MS Recovery from Hair: 5 authentic samples.
- LC/MS/MS Precision, Linearity, LLOQ/LOD: These studies involved spiked samples rather than a separate "test set" of authentic patient samples, with varying numbers of replicates (e.g., 5 analyses, 5 samples for 5 days).
- Sample Stability during Shipping and Storage: 6 samples for shipping stability and another 6 samples for storage stability.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Experts:
The primary "ground truth" for the comparison study and for confirming the EIA results is the Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS) method. This is a laboratory-based analytical method, not directly dependent on expert human interpretation of images or clinical signs. The document does not mention human experts establishing ground truth for the test set.
4. Adjudication Method for the Test Set:
Not applicable, as the ground truth is established by the LC/MS/MS analytical method, which is a quantitative measurement, not subject to human adjudication in the traditional sense of multiple readers interpreting a case. The LC/MS/MS confirms positive cotinine levels above a certain cutoff (100 pg cotinine/mg hair with presence of hydroxycotinine at or above 10 pg/mg hair).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done:
No, an MRMC comparative effectiveness study was not done. The device is an in vitro diagnostic assay, not an imaging device or AI algorithm requiring human interpretation. The comparison is between the new EIA screening method and the confirmatory LC/MS/MS method.
6. If a Standalone Study (algorithm only without human-in-the-loop performance) was done:
Yes, a standalone study of the device (Psychemedics Microplate EIA for Cotinine in Hair) was performed in comparison to the LC/MS/MS confirmatory method, which serves as the "gold standard" ground truth. The EIA itself operates independently without direct human intervention in the interpretation of its results (beyond reading the microplate reader output). The final confirmed analytical result is obtained by LC/MS/MS.
7. The Type of Ground Truth Used:
The ground truth used is an alternative chemical method, specifically Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS), which is considered a highly specific and sensitive analytical technique for cotinine detection. This is a form of laboratory/analytical ground truth. The LC/MS/MS analysis uses a cutoff of 100 pg cotinine/mg hair (after extensive washing) with the presence of hydroxycotinine at or above 10 pg/mg hair.
8. The Sample Size for the Training Set:
The document does not explicitly mention a "training set" in the context of machine learning. The device is a traditional enzyme immunoassay (EIA). The performance studies involve validation of the assay's characteristics (precision, linearity, cross-reactivity, etc.) using spiked samples, negative controls, and a limited number of authentic samples for comparison studies. There isn't a "training set" in the sense of data used to train an AI model.
9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no specific "training set" for an AI model. The calibrators and control materials for the EIA and LC/MS/MS are prepared using drug stocks from commercial vendors with certificates of analysis, and their concentrations are confirmed by LC/MS/MS.
§ 862.3220 Carbon monoxide test system.
(a)
Identification. A carbon monoxide test system is a device intended to measure carbon monoxide or carboxyhemoglobin (carbon monoxide bound to the hemoglobin in the blood) in blood. Measurements obtained by this device are used in the diagnosis and treatment of or confirmation of carbon monoxide poisoning.(b)
Classification. Class I (general controls). 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.