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510(k) Data Aggregation
(269 days)
The Psychemedics Microplate EIA For Benzodiazepines in Hair is an in vitro diagnostic device for the qualitative detection of benzodiazepines in hair. The assay is intended for use in workplace settings for the qualitative analysis of human head and body hair. The assay uses a cutoff calibrator of 1 ng oxazepam/10 mg hair.
The immunoassay 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 Benzodiazepines. The screening portion of the test system consists of microplate wells coated with Oxazepam conjugated to bovine serum albumin (BSA), the prepared hair sample, a cutoff calibrator added to the sample at a concentration of 1 ng Oxazepam/10 mg hair, monoclonal mouse anti-Oxazepam antibody, goat anti-mouse 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.
The confirmation assay consists of a AB Sciex API 3200 LC/MS/MS (Serial numbers AA24661109 and AA28841310) linked to two Shimazu LC-20AD Micro pumps and a Leap Technologies PAL autosampler.
The provided text describes the performance characteristics of the "Psychemedics Microplate EIA for Benzodiazepines in Hair" (the "device") and its supporting studies. The information is presented in the context of a 510(k) premarket notification to the FDA, demonstrating substantial equivalence to a predicate device.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" for each performance metric in a pass/fail format. Instead, it describes validated ranges and outcomes that were considered acceptable for demonstrating the device's performance. The reported performance is directly from the tables and text provided.
| Performance Characteristic | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Immunoassay Precision | Consistent positive/negative calls across concentrations and replicates, especially near the cutoff. | Intra-Assay:- Negative, 25%, 50%, 75% of cutoff: 15/0 (Negative/Positive) - Cutoff: 7/8 (Negative/Positive) - 125%, 150%, 175%, 200% of cutoff: 0/15 (Negative/Positive) Inter-Assay:- Negative, 25%, 50%, 75% of cutoff: 75/0 (Negative/Positive) - Cutoff: 43/32 (Negative/Positive) - 125%, 150%, 175%, 200% of cutoff: 0/75 (Negative/Positive) |
| LC-MS/MS Precision | %CV of 10% or less for each level tested; concentrations within ± 15% of target; correlation coefficient >0.995; mean of replicates within ± 15% of predicted. | Alprazolam: %CV range 2.96% - 11.45% (n=5 samples, triplicate reps) Lorazepam: %CV range 4.83% - 7.42% (n=4 samples, triplicate reps) Diazepam: %CV range 0.91% - 12.77% (n=5 samples, triplicate reps) Nordiazepam: %CV range 3.81% - 7.75% (n=4 samples, triplicate reps) Oxazepam: %CV range 2.25% - 10.82% (n=4 samples, triplicate reps) Temazepam: %CV range 1.99% - 13.12% (n=5 samples, triplicate reps) |
| LC-MS/MS Linearity | %CV ≤ 10%, concentrations within ± 15% of target, correlation coefficient >0.995, mean of replicates within ± 15% of predicted value based on linear regression. | All conditions met, establishing a linear range of 0.05 to 20.0 ng/10 mg hair for Alprazolam, Lorazepam, Diazepam, Nordiazepam, and Temazepam. |
| LC-MS/MS Detection Limit (LLOQ) | Analyte response at LLOQ ≥ 5 times blank response; identifiable, discrete, reproducible peak; precision (CV) ≤ 20%; accuracy within 20% of nominal. | LLOQ of 0.05 ng/10 mg hair for all six benzodiazepines, with all acceptance criteria satisfied. |
| Immunoassay Specificity (Cross-reactivity) | N/A (listed cross-reactivity percentages) | Varies significantly by compound (e.g., Clobazam 550%, Oxazepam 100%, Lorazepam 13%, 7-aminoclonazepam <0.3%). This data informs potential false positives/negatives based on specific benzodiazepines. |
| Immunoassay Specificity (Interference) | No positive or negative interference observed. | No positive or negative interference observed from 70+ structurally unrelated compounds tested at 100 ng/10 mg hair. |
| LC-MS/MS Specificity (Cross-reactivity) | No cross-reactivity observed with structurally related compounds. | No cross-reactivity observed for Clonazepam, Estazolam, Flurazepam, Meprobromate, Midazolam, Nitrazepam, Prazepam, Triazolam, and Zolpidem. |
| LC-MS/MS Specificity (Interference) | No interference observed with structurally unrelated compounds. | No interference observed from 30+ structurally unrelated compounds including common drugs and metabolites. |
| Immunoassay Accuracy (Method Comparison) | High concordance with confirmatory LC/MS/MS method with clear explanation of discordant results based on established cutoffs. | 382 hair samples (318 head, 64 body) compared to LC/MS/MS. - True Negative: 233 - True Positive (high): 107 - False Positive (-0.5x cutoff): 5 - False Positive (near cutoff 0.5x-1x): 19 - False Negative (near cutoff 1x-1.5x): 0 - False Negative (+1.5x cutoff): 0 Discordant results (24 samples) were analyzed, and concentrations were calculated based on cross-reactivities, showing that positive immunoassay results for samples with "LC/MS/MS Result" below the 1 ng cutoff were frequently due to the summed concentration of benzodiazepines present in the sample being above the effective cutoff when accounting for cross-reactivity. Examples show calculated effective concentrations ranging from 0.255 to 0.961 ng/10 mg hair for these discordant samples. |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Immunoassay Precision: 15 replicates per concentration for Intra-Assay (9 concentrations), 75 replicates per concentration for Inter-Assay (9 concentrations over 5 days).
- LC-MS/MS Precision: For each of the six benzodiazepines, between 4 and 5 authentic samples were tested in triplicate.
- LC-MS/MS Linearity: 8 concentrations plus a zero concentration sample were evaluated. The number of replicates per concentration is stated as five (implied for linearity validation criteria).
- LC-MS/MS LLOQ: Not explicitly stated how many samples were used, but acceptance criteria were met.
- Immunoassay Specificity (Cross-reactivity): Various concentrations of 27 benzodiazepines. Not specified how many unique samples/tests per compound.
- Immunoassay Specificity (Interference): At least 70 unique compounds, each tested at 100 ng/10 mg hair on samples spiked with oxazepam at cutoff and ±50% of cutoff. Not specified how many replicates per compound.
- LC-MS/MS Specificity (Cross-reactivity): 9 structurally related compounds. Not specified how many unique samples/tests per compound.
- LC-MS/MS Specificity (Interference): 30+ structurally unrelated compounds. Not specified how many unique samples/tests per compound.
- Accuracy (Method Comparison): 382 hair samples (318 head hair, 64 body hair).
- Data Provenance: The general context implies that the data was collected at the manufacturer's site ("Psychemedics plans to perform this test at one site"). The type of data appears to be prospective as it involves experimental testing of the device's performance characteristics. The document does not specify the country of origin of the data beyond the manufacturer's location in Culver City, CA, USA, and the FDA's US location.
- For the accuracy study, the samples represented diverse hair colors (159 black, 197 brown, 8 blond, 4 red, 14 gray) and ethnicities (175 Caucasian, 40 African-American, 125 Hispanic, 41 Asian subjects). This suggests real-world samples were used.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not mention the use of human experts or readers to establish ground truth for the analytical studies. The ground truth for the test set is established through confirmatory chemical methods, specifically Liquid Chromatography/Mass spectrometry/Mass spectrometry (LC/MS/MS), which is the gold standard for quantitative drug analysis in forensic and clinical toxicology. These methods are analytical and do not typically involve human expert interpretation for "ground truth" in the same way imaging studies might.
4. Adjudication Method for the Test Set
Not applicable. The ground truth is established by a definitive chemical analysis (LC/MS/MS), not through human review or adjudication of qualitative results.
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
Not applicable. This device is an in vitro diagnostic (IVD) test, specifically an immunoassay for drug detection. It is not an AI-powered image analysis tool that assists human readers/interpreters. Therefore, MRMC studies and human reader improvement are not relevant to this type of device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are essentially "standalone" performance evaluations of the device technology (immunoassay and LC/MS/MS). The immunoassay provides a preliminary screening result, and the LC/MS/MS provides a confirmed analytical result. Human involvement is in operating the instruments and interpreting the quantitative data, rather than forming a diagnostic opinion that is then augmented or compared to an AI algorithm.
7. The Type of Ground Truth Used
The primary ground truth used for evaluating the device's performance is chemical confirmation via Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC/MS/MS). This is considered the "confirmatory method" and is explicitly described as "a more specific alternate chemical method must be used to obtain a confirmed analytical result." This is a highly objective and quantitative method for identifying and measuring specific benzodiazepines. The document also points out that the immunoassay results (qualitative) were interpreted relative to the LC/MS/MS quantitative results, taking into account cross-reactivity for clarity in discordant cases.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI models. This device is an immunoassay, which is a biochemical assay, not an AI algorithm that requires training data in the traditional sense. The studies described demonstrate the analytical performance of the immunoassay and the confirmatory LC/MS/MS method.
9. How the Ground Truth for the Training Set Was Established
As there is no mention of a "training set" for an AI algorithm, this question is not applicable to the presented information. The ground truth for the validation/test samples (as discussed in point 7) was established through LC/MS/MS.
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