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The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is an enzyme immunoassay with a cutoff of 10 ng/mL in neat oral fluid collected by Quantisal II Oral Fluid Collection Device. The assay is intended for the qualitative and semi-quantitative analysis of PCP in human oral fluid with clinical analyzers. This assay is calibrated against PCP.

The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.

The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical must be used in order 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. Clinical consideration and professional judgment should be applied to any test result. particularly when preliminary positive results are used.

The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is an in vitro diagnostic test to detect the presence of PCP in human oral fluid samples collected by Quantisal or Quantisal II Oral Fluid Collection Device.

Here's a breakdown of the acceptance criteria and the study that demonstrates the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The document does not explicitly state "acceptance criteria" in a separate table or section with numerical targets. Instead, it presents performance characteristics and implies that the observed results met the requirements for substantial equivalence. The key performance indicators evaluated were precision, interference, linearity/recovery, stability, calibration duration, and method comparison.

For the purpose of this analysis, I will infer the acceptance criteria from common expectations for FDA-cleared diagnostic devices, particularly for qualitative and semi-quantitative assays, and present the reported device performance against these implicit criteria.

Table of Acceptance Criteria and Reported Device Performance

Study Details

The provided document describes a series of laboratory performance studies to demonstrate the substantial equivalence of the SEFRIA PCP Oral Fluid Enzyme Immunoassay.

1. Sample size used for the test set and the data provenance:

   • Precision (Quantitative Test Set): For each concentration level (0 ng/mL, 2.5 ng/mL, 5 ng/mL, 7.5 ng/mL, 10 ng/mL, 12.5 ng/mL, 15 ng/mL, 17.5 ng/mL, 20 ng/mL), there were 60 determinations.
     • Data Provenance: Drug-free negative oral fluid was "spiked" to target concentrations. This is a controlled laboratory study, not directly from human patients. The "Data for the candidate device used with Quantisal II device were reported in K181135" indicates that some results, specifically for Quantisal II, were referenced from a previous submission, suggesting a mix of new and previously generated data on the device platform.
   • Interference - Orally Used Endogenous Compounds: For each compound tested (e.g., Teeth Whitener, Cigarette), samples were prepared by volunteers using the substance, then spiked with PCP at ±25% of the cutoff. The exact number of samples for each compound is not specified, but the conclusion states "No interference was observed with any of the compounds," implying sufficient testing.
     • Data Provenance: Oral fluid collected from "volunteers" after use of substances. This implies prospective collection in a controlled setting.
   • Linearity/Recovery: Multiple pools were created by serial dilution. Each pool was tested in triplicate. (Number of distinct samples not explicitly stated, but 13 concentration levels were tested in triplicate for 39 total runs of the assay).
     • Data Provenance: Drug-free oral fluid pools spiked with PCP. Controlled laboratory study.
   • PCP Stability in Oral Fluid: Samples spiked with PCP were stored and tested periodically. The exact number of samples per time point is not specified but referenced baseline concentration results.
     • Data Provenance: Spiked drug-free negative oral fluid. Controlled laboratory study.
   • Calibration Duration: Samples spiked with PCP at ±25% of the cutoff were tested at time points up to 14 days. Exact number of samples per time point not specified.
     • Data Provenance: Spiked drug-free negative oral fluid. Controlled laboratory study.
   • Method Comparison (Clinical Test Set): 80 deidentified, unaltered clinical oral fluid samples.
     • Data Provenance: Obtained from drug treatment facilities. This indicates retrospective collection from human subjects in a real-world clinical setting.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • Precision, Interference, Linearity/Recovery, Stability, Calibration Duration: For these analytical studies, the ground truth was established by carefully controlled spiking concentrations of PCP, confirmed by mass spectrometry (LC-MS/MS) before collection (for precision) or by reference methods. This doesn't involve "experts" in the clinical sense, but rather relies on the accuracy of the laboratory's preparation and analytical techniques.
   • Method Comparison: For the 80 clinical samples, the ground truth was established by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). This is a highly sensitive and specific confirmatory analytical method and acts as the gold standard, so no human experts are used for this type of ground truth.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

   • Adjudication methods (like 2+1 or 3+1 consensus by experts) are typically used in studies involving subjective interpretation, such as imaging or pathology, where human readers create the initial "truth."
   • In this context, where the ground truth is established by objective analytical methods (LC-MS/MS, or precisely prepared spiked samples), there is no human adjudication process described or needed. The analytical results are the ground truth.

4. If a multi-reader, multi-case (MRMC) comparative effectiveness study was done:

   • No, an MRMC comparative effectiveness study was not done. This type of study (comparing human readers with and without AI assistance) is not applicable to an in vitro diagnostic device like an enzyme immunoassay, which is a standalone automated analytical test. The "readers" here are the instruments and their output, not human interpreters.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • Yes, the performance studies described are inherently "standalone." The SEFRIA PCP Oral Fluid Enzyme Immunoassay is an automated system (used with clinical analyzers like the Beckman Coulter AU480). All performance characteristics (precision, linearity, method comparison, etc.) evaluate the device's analytical output without human intervention in the interpretation of the primary result. Human intervention comes after the preliminary positive result, where confirmation by GC-MS or LC-MS/MS is required.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • Primary Ground Truth: For the method comparison and for confirming spiked concentrations, the analytical gold standard was Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
   • Other Ground Truths: For precision, linearity/recovery, stability, and calibration duration, the ground truth was established by precisely prepared spiked samples with known concentrations, often verified by LC-MS/MS.

7. The sample size for the training set:

   • The document describes performance validation studies for the device, not the development or training of a machine learning model. Therefore, a "training set" in the context of AI/ML is not explicitly mentioned or relevant here. The device is an enzyme immunoassay, which operates on chemical reactions and optical detection, not a machine learning algorithm that requires a training set.

8. How the ground truth for the training set was established:

   • As there's no mention of a machine learning "training set," this question is not applicable. The assay's "learning" or optimization would have occurred during its internal development and formulation, not through an enumerated "training set" in the context of an FDA submission for an in vitro diagnostic immunoassay.

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The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 10 ng/mL in neat oral fluid collected with the Quantisal II Oral Fluid Collection Device. The assay is intended for the qualitative and semi-quantitative analysis of PCP in human oral fluid with clinical analyzers. This assay is calibrated against PCP. This in vitro diagnostic device is for prescription use only.

The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.

The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical must be used in order 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. Clinical consideration and professional judgment should be applied to any test result, particularly when preliminary positive results are used.

The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is a sensitive in vitro diagnostic test to detect the presence of PCP in human oral fluid samples collected with the Quantisal II Oral Fluid Collection Device.

Quantisal II Oral Fluid Collection Device is a collection system comprised of a dual pad collector and transport vials. The dual pad collector is separated after collection of oral fluid from a subject's mouth enabling each specimen-saturated collection pad to be placed into its own transport vial. The split specimen (referred to as "A" and "B") allows for one sample to be tested in a screening assay and confirmed by a quantitative laboratory method (such as liquid chromatography tandem mass spectrometry [LC-MS/MS] and the second sample to be stored for secondary confirmation if needed.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Device Name: Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" as a separate list with pass/fail values. Instead, it describes various performance studies and their results. The implicit acceptance criteria are that the device performs reliably and consistently, and that its results correlate well with a confirmatory method (LC-MS/MS).

However, based on the provided tables, we can infer some key performance metrics and their results:

• 0, 2.5, 5, 7.5 ng/mL (negative concentrations): 60/60 Negative.
• 12.5, 15, 17.5, 20 ng/mL (positive concentrations): 60/60 Positive.
• 10 ng/mL (Cutoff): 29-32 Negative / 28-31 Positive (expected result at cutoff).
  Semi-Quantitative (Quantisal II "A" & "B"):
• Mean concentrations for spiked samples are close to the expected values (e.g., 0.5 ng/mL for 0 ng/mL, 20.2 ng/mL for 20 ng/mL), demonstrating accurate semi-quantification. At the cutoff (10 ng/mL), results show an appropriate split between negative and positive calls, consistent with the nature of a cutoff analysis. |
  | Specificity/Cross-Reactivity | Ability to exclusively determine PCP without significant interference from structurally and functionally similar compounds. Compounds spiked to yield PCP equivalent of 10 ng/mL. | Cross-Reactive (Positive at 10 ng/mL equivalence): Amitriptyline, Chlorpromazine, Clomipramine, Cyclobenzaprine, Diphenhydramine, Doxepin, 4-Hydroxyphencyclidine (PCHP - 11.76% cross-reactivity), Imipramine, Methoxetamine, Thioridazine.
  **Non-Cross-Reactive (Negative at 15 ng/mL). This indicates excellent diagnostic agreement. |

2. Sample Size Used for the Test Set and Data Provenance

The document describes several test sets for different performance characteristics:

• Precision/Cutoff Characterization:
  • Sample Size: 60 determinations at each of 9 concentration levels (0, 2.5, 5, 7.5, 10, 12.5, 15, 17.5, 20 ng/mL) for both "A" and "B" collectors. This totals 60 x 9 x 2 = 1080 individual tests across 15 days, two runs per day, with two collections per run.
  • Data Provenance: Drug-free negative urine spiked to specific concentrations. The origin of the urine itself is not specified but it's an artificially prepared test set.
• Specificity and Cross-Reactivity:
  • Sample Size: Not explicitly stated as a number of individual test runs per compound, but implies sufficient testing to determine cross-reactivity for 18 listed compounds.
  • Data Provenance: Drug-free oral fluid spiked with various compounds. Origin of the oral fluid is not specified, but it's an artificially prepared test set.
• Interference – Structurally Unrelated Compounds:
  • Sample Size: Not explicitly stated, but includes testing for over 70 compounds.
  • Data Provenance: Drug-free oral fluid containing PCP at ±25% of the cutoff, spiked with potential interferents. Origin of the oral fluid is not specified, but it's an artificially prepared test set.
• Interference – Endogenous Compounds and Exogenous Compounds:
  • Sample Size: Not explicitly stated for spiked compounds. For orally used products, likely tested with volunteers (number not specified for this specific section, but volunteer numbers are mentioned in other collection device studies).
  • Data Provenance: Drug-free oral fluid containing PCP at ±25% of the cutoff (for spiked compounds) or collected from volunteers after substance use.
• Interference – pH:
  • Sample Size: Not explicitly stated, but tested across 9 pH values (3.0 to 11.0).
  • Data Provenance: Drug-free oral fluid containing PCP at ±25% of the cutoff, adjusted to various pH values.
• Linearity/Recovery:
  • Sample Size: 13 concentration levels, each tested in triplicate for both "A" and "B" collectors. This totals 13 x 3 x 2 = 78 individual tests.
  • Data Provenance: Drug-free oral fluid pooled and spiked with high concentrations of PCP, then serially diluted.
• Calibration Duration:
  • Sample Size: Not explicitly stated, but tested at multiple time points up to 14 days.
  • Data Provenance: Drug-free negative oral fluid spiked with PCP at ±25% of the cutoff.
• PCP Stability in Oral Fluid:
  • Sample Size: Not explicitly stated, but tested by LC-MS/MS at multiple time points and storage conditions.
  • Data Provenance: Drug-free negative oral fluid spiked with PCP at +50% of the cutoff.
• Sample Transportation Stability:
  • Sample Size: Not explicitly stated, but tested in replicates of two against a reference sample across varying temperatures.
  • Data Provenance: Drug-free negative oral fluid spiked with PCP at ±50% of the cutoff.
• Sample Recovery:
  • Sample Size: Not explicitly stated.
  • Data Provenance: Drug-free negative oral fluid spiked with PCP at ±25% and +50% of the cutoff.
• Quantisal II Sample Volume:
  • Sample Size: 50 oral fluid samples from healthy volunteers and an additional 75 oral fluid samples from known drug users. Total = 125 unique samples.
  • Data Provenance: Prospective collection from healthy volunteers and known drug users. Country of origin not specified.
• Quantisal II Sample Collection Time:
  • Sample Size: 50 oral fluid samples from volunteers and 75 oral fluid samples from known drug users. Total = 125 unique samples.
  • Data Provenance: Prospective collection from healthy volunteers and known drug users. Country of origin not specified.
• Method Comparison:
  • Sample Size: 80 de-identified, unaltered clinical oral fluid samples.
  • Data Provenance: Retrospective and prospective. "Obtained from drug treatment facilities." Country of origin not specified, but likely within the US, given the FDA submission. The samples are clinical, not contrived.

3. Number of Experts and Qualifications for Ground Truth

• The document does not mention the use of human experts to establish ground truth for any of the test sets in the traditional sense of medical image interpretation or clinical diagnosis.
• For chemical assays, "ground truth" is typically established by reference methods or by precisely known concentrations of analytes.

4. Adjudication Method for the Test Set

• Adjudication methods like 2+1 or 3+1 (common in medical image reading studies) are not applicable here as the device is a chemical immunoassay, not an AI for image interpretation.
• The ground truth for most analytical performance studies (precision, specificity, linearity, etc.) was established by known spiked concentrations of PCP or other compounds.
• For the Method Comparison study, the ground truth was established by a confirmatory method: Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), which is considered the gold standard for drug quantification. There was no "adjudication" between multiple experts; rather, the device's results were compared against the definitive LC-MS/MS measurements.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

• No MRMC comparative effectiveness study was done. This type of study is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) and the impact of AI assistance on their performance.
• This device is an automated in vitro diagnostic immunoassay for chemical analysis, not a system intended to assist human readers in making a diagnosis from complex data patterns that require human cognitive input.

6. Standalone Performance

• Yes, the studies primarily assessed standalone (algorithm only) performance. The Immunalysis SEFRIA PCP Oral Fluid Enzyme Immunoassay is an automated system run on clinical analyzers (specifically, the Beckman Coulter AU480 chemistry analyzer was used for these studies).
• All the precision, specificity, linearity, stability, and pH interference studies directly demonstrate the standalone performance of the assay and collection device combination.
• The "Method Comparison" study compares the device's standalone output to the LC-MS/MS reference, further confirming its standalone accuracy.

7. Type of Ground Truth Used

The ground truth varied depending on the performance characteristic being evaluated:

• Spiked Concentrations: For precision, specificity, interference, linearity, calibration duration, stability, transportation stability, and sample recovery, the ground truth was based on precisely known concentrations of PCP or other compounds spiked into drug-free oral fluid or urine.
• Confirmatory Method (LC-MS/MS): For the Method Comparison study, the ground truth for clinical samples was established by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), which is the preferred confirmatory method for drug analyses.
• Measured Physical Properties: For sample volume and collection time consistency, the ground truth was established by physical measurements (weighing for volume, stopwatch for time).

8. Sample Size for the Training Set

The document is a 510(k) submission for a diagnostic kit, not an AI/ML model that requires a "training set" in the computational sense. Therefore, there is no specific training set described for the device. The "training" for such devices typically involves the manufacturer's internal development and optimization processes, which are not detailed in a 510(k) summary.

9. How the Ground Truth for the Training Set was Established

As there is no "training set" for an AI/ML model, this question is not applicable. The development of the assay and its reagents would have relied on standard chemical and biological research and development practices, using analytical standards and reference materials to establish optimal performance.

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