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The RapidFRET Oral Fluid Assay for Methamphetamine is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for methamine at 50 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Methamine Calibrators and RapidFRET Oral Fluid Methamphetamine Controls are intended for use only with appropriate RapidFRET Oral Fluid Assay products and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive controls are used to monitor laboratory systems, operators, precision. accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for Methamphetamine is an In Vitro Diagnostic competitive immunoassay used to detect methamphetamine in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.

The provided text describes the RapidFRET Oral Fluid Assay for Methamphetamine. Here's an analysis of the acceptance criteria and the study conducted:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state formal "acceptance criteria" through a defined table or specific performance thresholds for sensitivity, specificity, or accuracy that the device must meet. Instead, the performance characteristics are presented as results from various studies, which imply the expected performance for a successful premarket notification. The de facto acceptance criteria appear to be substantial equivalence to the predicate device (Lin-Zhi International, Inc., LZI Oral Fluid Methamphetamine Enzyme Immunoassay (K131652)) and demonstrating acceptable analytical performance.

However, based on the provided data, we can infer some performance expectations and list the reported outcomes:

• RapidFRET POS / Confirmed POS:
  • ≥150% Cutoff: 39
  • 100-150% Cutoff: 5
  • 50-100% Cutoff: 2‡ (These would ideally be negative by the screening cutoff)

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The RapidFRET Oral Fluid Assay for Cocaine is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for cocaine at 20 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay is calibrated with Cocaine and provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Cocaine Calibrator Set and RapidFRET Oral Fluid Cocaine Control Set are intended for use with the RapidFRET Oral Fluid Assay for Cocaine and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for Cocaine is an In Vitro Diagnostic competitive immunoassay used to detect cocaine in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.

Here's a breakdown of the acceptance criteria and study information for the RapidFRET Oral Fluid Assay for Cocaine, as extracted from the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

• 0%, 25%, 50% of cutoff (0, 5, 10 ng/mL): 100% Negative (0% Positive)
• 75% of cutoff (15 ng/mL): 99% Negative (1% Positive)
• 100% of cutoff (20 ng/mL): 52% Negative, 48% Positive
• 125% of cutoff (25 ng/mL): 5% Negative, 95% Positive
• 150%, 175%, 200% of cutoff (30, 35, 40 ng/mL): 100% Positive (0% Negative)
  Conclusion: Analytical sensitivity is between 75% and 125% of cutoff, with expected results achieved at 97% frequency within this range. |
  | Accuracy / Correlation with MS Quantitation | High agreement with confirmatory methods (GC/MS or LC/MS/MS) for both positive and negative samples. | Clinical Samples (n=294):
• Low Negative (30 ng/mL by MS): 0 RapidFRET NEG, 55 RapidFRET POS.
  Conclusion: Accurate >99% of the time in neat oral fluid samples. |
  | Cross-Reactivity & Analytical Specificity | Limited and identified cross-reactivity with structurally similar compounds, and no significant interference from common substances, foods, or dental products. | Structurally Related Compounds (171 compounds screened, 13 identified):
• Benzoylecgonine: 18 ng/mL (111% cross-reactivity)
• Cocaethylene: 15 ng/mL (133% cross-reactivity)
• Cinnamoylcocaine: 224 ng/mL (8.2% cross-reactivity)
• Others: Chlorpromazine, Clomipramine, Cyclobenzaprine, Ecgonine, Ecgonine methyl ester, Imipramine, Isoxsuprine (HMMC), Norcocaine, Perphenazine, Thioridazine, Trifluoperazine showed cross-reactivity below 30,000 ng/mL (0.1% to 2.4%).
  Common Substances: All tested compounds (HSA, ethanol, baking soda, blood, etc.), pH variations (5-9), and various mouth/food products (mouthwash, cough syrup, cranberry juice, etc.) showed expected NEG results with 10 ng/mL cocaine and POS results with 30 ng/mL cocaine (i.e., no significant interference at concentrations tested). |

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

• Precision and Analytical Sensitivity Test Set: For precision, 180 samples were tested for each concentration level (0%, 25%, 50%, 75%, 100%, 125%, 150%, 175%, 200% of cutoff). This involved triplicate samples per run, 4 times daily for 5 days using 3 independent lots of reagent.
• Correlation with MS Quantitation Test Set: 294 samples were collected.
• Data Provenance:
  • Precision and Analytical Sensitivity: "Negative oral fluid pools were spiked with cocaine..." This suggests a controlled laboratory setting, likely in the US where the company is based.
  • Correlation with MS Quantitation: "Neat oral fluid was collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for opiates." This implies prospective collection from human subjects, but the country of origin is not explicitly stated. Given the submission to the FDA, it's highly probable the study was conducted in the US.
  • Cross Reactivity and Analytical Specificity: Compound library testing and common substance/food testing were conducted in a laboratory setting.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

• Precision and Analytical Sensitivity: For this study, the ground truth was established by spiking known concentrations of cocaine into negative oral fluid. No independent experts were explicitly mentioned for determining the "ground truth" for the spiked samples, as the concentrations were precisely controlled.
• Correlation with MS Quantitation: The ground truth was established by confirmatory testing using GC/MS or LC/MS/MS. While these are highly accurate analytical methods, the text does not specify the number or qualifications of experts performing or interpreting these confirmatory tests. It's standard practice that such analyses are performed by qualified laboratory personnel.
• Cross Reactivity and Analytical Specificity: The ground truth for cross-reactivity studies was based on known concentrations of the spiked compounds and their expected interaction with the assay, verified by the assay itself relative to the cutoff. For common substances, the ground truth was the known presence/absence of cocaine spikes and the expectation of no interference from the common substance. No external experts for ground truth establishment are explicitly stated beyond the analytical methods.

4. Adjudication Method for the Test Set

The provided text does not describe an explicit adjudication method for discrepant results, such as 2+1 or 3+1. For the correlation study, samples were "sent for confirmatory testing (GC/MS or LC/MS/MS)" after initial screening. This suggests that the confirmatory method served as the de-facto gold standard to resolve any initial screening discrepancies, rather than an expert panel adjudication process from multiple readers/interpreters of the device's results.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not described in this document. This device is an in-vitro diagnostic (IVD) assay where the output is a qualitative (positive/negative) result from an automated instrument, not an image or data requiring human interpretation for diagnosis in the same way an AI for medical imaging would. The "human-in-the-loop" aspect here refers to a lab technician performing the test and interpreting the instrument's output based on established cutoffs.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Device Was Done

Yes, the studies reported are standalone performance studies of the RapidFRET Oral Fluid Assay for Cocaine. The device is a "homogeneous time-resolved fluorescence assay" designed for use on an "Integrated Workstation." The performance data (precision, accuracy, cross-reactivity) refer to the analytical performance of the assay system itself, providing a qualitative (positive/negative) result directly, without requiring human interpretation of complex patterns or classifications beyond reading the instrument's output against the defined cutoff. The "human-in-the-loop" here is limited to sample collection, loading, and result reporting, rather than diagnostic interpretation.

7. The Type of Ground Truth Used

• Precision and Analytical Sensitivity: Spiked known concentrations of cocaine.
• Correlation with MS Quantitation: Confirmatory analytical methods (GC/MS or LC/MS/MS).
• Cross Reactivity and Analytical Specificity: Known concentrations of spiked compounds and their expected behavior (presence/absence of cocaine for the interference studies).

8. The Sample Size for the Training Set

The document does not explicitly state the sample size for a "training set." This is common for this type of IVD device where development often involves iterative optimization and validation across various sample types and spike levels, rather than a distinct "training set" and "test set" in the context of machine learning. The studies described are more akin to validation studies demonstrating the device's performance characteristics.

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

Since a distinct "training set" is not detailed, the method for establishing ground truth for training is not provided. However, generally, for the development of such assays, manufacturers would leverage:

• Well-characterized samples: Including known positive and negative samples, and samples spiked with varying concentrations of the analyte and potential interferents.
• Reference methods: Using established gold-standard analytical techniques (like GC/MS or LC/MS/MS) to confirm analyte concentrations in samples used for assay development and optimization.

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The RapidFRET Oral Fluid Assay for Amphetamine is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for amphetamine at 50 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Amphetamine Calibrator Set and RapidFRET Oral Fluid Amphetamine Control Set are intended for use only with the RapidFRET Oral Fluid Assay for Amphetamine and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive controls are used to monitor laboratory systems, operators, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for Amphetamine is an In Vitro Diagnostic competitive immunoassay used to detect amphetamine in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.

The provided document describes the RapidFRET Oral Fluid Assay for Amphetamine and its performance characteristics. Here's a breakdown of the acceptance criteria and study details:

1. Acceptance Criteria and Reported Device Performance

The document implicitly defines acceptance criteria through the performance study results. While specific percentage targets aren't always explicitly stated as "acceptance criteria," the reported performance demonstrates what the device achieved and, by extension, what was considered acceptable for substantial equivalence.

• False Positives: 14 samples (out of 335 true negatives by MS) (12 due to MDA/DMC cross-reactivity).
• False Negatives: 2 samples (out of 43 true positives by MS) (amphetamines at 71.6 ng/mL and 70.3 ng/mL). |
  | Cross-Reactivity | Minimal or acceptable cross-reactivity with other substances | Some structurally related compounds showed cross-reactivity at varying levels (e.g., MDA at 53%, Benzodioxolylbutanamine at 13%).
  Many other substances and common products showed no interference. |
  | Analytical Specificity | No interference from common substances, oral products, or pH variations | No interference seen from 167 structurally unrelated compounds.
  No interference from HSA, ethanol, baking soda, whole blood, hemoglobin, hydrogen peroxide, sodium chloride, cholesterol, denture adhesive, ascorbic acid, bilirubin, IgA, IgG, IgM, salivary α-amylase, or pH variations (5-9).
  No interference from antiseptic mouthwash, cough syrup, cranberry juice, orange juice, toothpaste, chewing tobacco, cigarettes, chewing gum, hard candy, teeth whitening strips, cola, water, antacid, coffee, and tea. |

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

• Precision Test Set Sample Size:
  • 3 lots were analyzed, 4 times daily, for a minimum of 20 days.
  • For each concentration level tested (0%, 25%, 50%, 75%, 100%, 125%, 150%, 175%, 200% of cutoff), the "N" value represents the total number of tests performed. These ranged from 263 to 294 for each concentration, across all lots.
• Correlation with MS Test Set Sample Size:
  • N = 415 neat oral fluid samples.
• Cross-Reactivity and Analytical Specificity Test Set Sample Size:
  • Approximately 167 different structurally related and unrelated compounds were tested.
  • Additional common substances (HSA, ethanol, baking soda, etc.), pH variations, and oral products (antiseptic mouthwash, coffee, etc.) were also tested individually or through volunteer samples.
• Data Provenance: The document does not explicitly state the country of origin. The studies appear to be prospective bench testing and clinical sample testing performed specifically for this submission. The "Correlation with MS Quantitation" study mentions samples collected "from volunteers potentially positive and negative for amphetamine."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The document does not mention the use of experts to establish ground truth.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method involving experts for interpretation of results. For the Correlation with MS Quantitation study, the "ground truth" was established by confirmatory testing using more specific alternate chemical methods such as GC/MS or LC/MS/MS.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic assay, where the output is a qualitative (positive/negative) result based on a measurement against a specific cutoff, not a diagnostic image or interpretation requiring multiple human readers.

6. If a Standalone Study (algorithm only without human-in-the-loop performance) was done

Yes, the studies presented describe the standalone performance of the RapidFRET Oral Fluid Assay for Amphetamine. The performance metrics (precision, accuracy, cross-reactivity, analytical specificity) are derived directly from the assay's output based on given samples, without human interpretation influencing the result. The device provides a "preliminary result," which then requires a human to potentially send the sample for confirmatory testing, but the performance data outlined specifically relates to the device's ability to generate that preliminary result.

7. The Type of Ground Truth Used

• Precision and Analytical Sensitivity: Controlled spiking of known concentrations of amphetamine into negative oral fluid pools.
• Correlation with MS Quantitation: Confirmatory analytical methods: GC/MS (Gas Chromatography/Mass Spectrometry) or LC/MS/MS (Liquid Chromatography/Mass Spectrometry/Mass Spectrometry). This represents a highly specific and accurate chemical analysis, often considered the "gold standard" for drug confirmation.
• Cross-Reactivity and Analytical Specificity: Controlled spiking of known concentrations of interfering substances into oral fluid samples with and without amphetamine, and analysis of oral fluid from volunteers after exposure to common oral products.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" as it would be understood for machine learning algorithms. This device is an immunoassay, which typically does not involve a separate training phase like AI/ML models. Its operational parameters are determined during assay development and validation, not through iterative training on a dataset.

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

As there is no explicit "training set" mentioned in the context of an AI/ML model, this question is not directly applicable. The performance characteristics are established through the validation studies described, which include controlled spiking experiments and correlation with a gold standard method.

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The RapidFRET Oral Fluid Assay for MDMA is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for Methylenedioxymethamphetamine at 50 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid MDMA Calibrator Set and RapidFRET Oral Fluid MDMA Control Set are intended for use only with the RapidFRET Oral Fluid Assay for MDMA and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for MDMA is an In Vitro Diagnostic competitive immunoassay used to detect MDMA in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive result. Controls are used to establish and monitor precision and accuracy.

Here's an analysis of the provided text to extract the requested information about the RapidFRET Oral Fluid Assay for MDMA:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the expected results and agreement percentages reported.

*Note: The 97% for MS NEG agreement is calculated from the provided table: 200 RapidFRET NEG when MS NEG, and 6+ RapidFRET POS when MS NEG (false positives). So, 200 / (200 + 6) = 200/206 ≈ 97%.

2. Sample Sizes and Data Provenance

• Precision and Analytical Sensitivity Test Set:
  • Sample Size: 279 at 0%, 279 at 25%, 278 at 50%, 279 at 75%, 279 at 100%, 278 at 125%, 263 at 150%, 294 at 175%, 278 at 200% of cutoff. These were spiked oral fluid pools.
  • Data Provenance: Not explicitly stated, but likely laboratory-prepared samples. It doesn't specify country of origin or if it's retrospective/prospective.
• Correlation with MS Quantitation Test Set:
  • Sample Size: 325 neat oral fluid samples.
  • Data Provenance: Collected from "volunteers potentially positive and negative for MDMA." This suggests prospective collection for the purpose of the study. Country of origin not specified, but the applicant's address is in California, USA, making it probable the study was conducted there.
• Cross Reactivity and Analytical Specificity Test Set:
  • Sample Size:
    • Structurally related compounds: A library of over 170 compounds. Specific numbers of samples per compound are not given, but they were spiked into neat oral fluid aliquots (likely 0, 25, 75 ng/mL MDMA).
    • Common substances: Not specified per substance, but implied to be multiple (volunteers for some, spiked aliquots for others).
  • Data Provenance: Laboratory-prepared samples (spiked) and samples from volunteers.

3. Number of Experts and Qualifications for Ground Truth

• Precision and Analytical Sensitivity: No human experts were explicitly mentioned for ground truth. The ground truth was established by the known concentrations of MDMA spiked into the oral fluid pools.
• Correlation with MS Quantitation: The ground truth was established by GC/MS or LC/MS/MS results. No human experts are mentioned for interpreting these confirmatory tests, as they are analytical methods providing quantitative results.
• Cross Reactivity and Analytical Specificity: No human experts were explicitly mentioned. The ground truth was based on the known concentrations of MDMA and cross-reactants spiked into the samples, or the known consumption of common substances.

4. Adjudication Method for the Test Set

• Precision and Analytical Sensitivity: Not applicable, as samples were spiked at known concentrations.
• Correlation with MS Quantitation: Not applicable. GC/MS or LC/MS/MS provides a definitive analytical result, not a judgment requiring adjudication.
• Cross Reactivity and Analytical Specificity: Not applicable. Ground truth was based on known concentrations.

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

• No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic assay, not a medical imaging or interpretive device that typically involves human readers in this context. It performs a qualitative screen (positive/negative) based on a cut-off.

6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop)

• Yes, the studies presented are all standalone performance studies. The RapidFRET Oral Fluid Assay for MDMA is an automated laboratory assay that performs a qualitative screen without human interpretation involved in the direct result generation. The performance metrics (precision, analytical sensitivity, correlation with MS) directly reflect the algorithm's performance.

7. Type of Ground Truth Used

• Precision and Analytical Sensitivity: Known concentrations of spiked MDMA (analytical truth).
• Correlation with MS Quantitation: Confirmed analytical results by GC/MS or LC/MS/MS (gold standard analytical truth).
• Cross Reactivity and Analytical Specificity: Known concentrations of spiked compounds (analytical truth) and known consumption of common substances (experiential/known truth).

8. Sample Size for the Training Set

• The document does not specify a separate training set or its sample size. This type of immunoassay device is typically developed through chemical and biological experimentation to establish reagent formulations and cutoff values, rather than through machine learning training on a large dataset in the way a modern AI algorithm would be. The experiments described appear to be validation/verification studies.

9. How Ground Truth for the Training Set Was Established

• As no training set is explicitly mentioned, the establishment of ground truth for it is not described. The device's operational parameters (e.g., cutoff) would be derived from laboratory experiments during development.

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The RapidFRET Oral Fluid Assay for OPIATES is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for Opiates at 40 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay is calibrated against Morphine. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Calibrator Set and RapidFRET Oral Fluid Control Set are intended for use only with the RapidFRET Oral Fluid Assay for OPIATES and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to translate the sample measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, operators, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for Opiates is provided in an all liquid, ready to use format. Two reagents are provided included a drug specific reagent and a second competitive donor reagent. The kit is provided with reagents and microtiter plates. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy. Calibrators and controls are sold separately.

Here's an analysis of the acceptance criteria and the study proving device performance, based on the provided 510(k) summary for the RapidFRET Oral Fluid Assay for OPIATES:

Acceptance Criteria and Device Performance Study

The RapidFRET Oral Fluid Assay for OPIATES is a qualitative screening device intended to detect opiates in oral fluid. The acceptance criteria and supporting studies focus on the analytical performance of the device, particularly its precision, correlation with confirmatory methods, and analytical specificity (cross-reactivity).

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this diagnostic device are implied through the performance observed in the studies designed to demonstrate substantial equivalence to the predicate device. The key performance characteristics evaluated were precision (analytical sensitivity), correlation with mass spectrometry (GC/MS or LC/MS/MS), and cross-reactivity/analytical specificity.

• 0-75% of cutoff (0-30 ng/mL): 100% Negative (0% Positive)
• 125-200% of cutoff (50-80 ng/mL): 100% Positive (0% Negative)
• 100% of cutoff (40 ng/mL): 66% Positive, 34% Negative
  Conclusion: Analytical sensitivity is between 75% and 125% of cutoff, with expected results achieved at 100% frequency. |
  | Correlation with Confirmatory Methods (Accuracy) | High agreement between the device's screening results and a more specific alternate chemical method (GC/MS or LC/MS/MS) for both positive and negative samples, particularly within the clinically relevant concentration ranges. | Correlation Results (n=245 samples):
• Overall Agreement for Positive Samples (RapidFRET): >98% agreement with GC/MS or LC/MS/MS.
• Overall Agreement for Negative Samples (RapidFRET): 100% agreement with GC/MS or LC/MS/MS.
• Discordant Results: One sample was Positive by RapidFRET (Total Opiates = 36.5 ng/mL by LC/MS, where cutoff is 40 ng/mL). |
  | Analytical Specificity (Cross-Reactivity) | The device should not show significant cross-reactivity with structurally unrelated compounds or common substances/interferents at clinically relevant concentrations that would lead to false positive or false negative results, while appropriately reacting with structurally related opiate compounds. | Cross-Reactivity Results:
• Evaluated with 167 compounds (structurally related/unrelated, metabolites, OTC/prescription meds, drugs of abuse).
• 29 structurally related compounds cross-reacted below 30,000 ng/mL in the absence of morphine.
• 12 of these cross-reacted at 1000 ng/mL equivalence or less.
• Interference Study: Common substances (foods, dental products, pH, etc.) did not interfere, showing NEG results at 20 ng/mL Morphine and POS results at 60 ng/mL Morphine. |

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

• Precision/Analytical Sensitivity Test Set: For precision, samples were created by spiking negative oral fluid pools with Morphine at various concentrations (0%, 25%, 50%, 75%, 100%, 125%, 150%, 175%, and 200% of the 40 ng/mL cutoff). Three lots of the assay were run four times daily for a minimum of 20 days.
  • The total number of individual runs/data points (N) per concentration level varied from 263 to 294 (e.g., N=279 for 0% and 25%, N=278 for 50%, N=279 for 75%, N=279 for 100%, N=278 for 125%, N=263 for 150%, N=294 for 175%, N=278 for 200%).
  • Data Provenance: Retrospective, as negative oral fluid pools were "spiked" to create controlled samples. The origin of the negative oral fluid pools is not explicitly stated (e.g., country of origin, volunteer demographics).
• Correlation with MS Quantitation Test Set:
  • Sample Size: 245 neat oral fluid samples from volunteers potentially positive and negative for opiates.
  • Data Provenance: Prospective, as samples were collected from volunteers and then tested. The origin of the volunteers (e.g., country) is not specified. The samples were handled in a blinded and randomized manner for instrument operators.
• Cross-Reactivity and Analytical Specificity Test Set:
  • Sample Size: 167 different compounds (for cross-reactivity). For interference, common substances were tested (specific number of substances not explicitly stated, but includes HSA, ethanol, baking soda, whole blood, hemoglobin, hydrogen peroxide, sodium chloride, cholesterol, denture adhesive, ascorbic acid, bilirubin, lgA, lgG, IgM; various pH values; and items like mouthwash, cough syrup, etc., tested after volunteers used them).
  • Data Provenance: Retrospective for the spiked compound library. For common substances, it involved volunteer participation (prospective for the collection part for some items) and then spiking or testing original samples.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

• Precision/Analytical Sensitivity: The ground truth was established by precise spiking concentrations of Morphine into negative oral fluid pools. No human experts were involved in establishing this analytical ground truth.
• Correlation with MS Quantitation: The ground truth was established by confirmatory testing using GC/MS or LC/MS/MS. These are highly accurate analytical methods considered the gold standard for drug confirmation. The document does not specify the number or qualifications of the analysts performing the GC/MS or LC/MS/MS.
• Cross-Reactivity/Analytical Specificity: The ground truth was established by the known concentration of the spiked compounds and the known presence/absence of morphine. No human experts were involved in establishing this analytical ground truth.

4. Adjudication Method for the Test Set

• Precision/Analytical Sensitivity, Cross-Reactivity/Analytical Specificity: No adjudication method was mentioned as these were analytical studies with predefined concentrations and expected outcomes.
• Correlation with MS Quantitation: The comparison was directly between the RapidFRET assay results and the established gold-standard GC/MS or LC/MS/MS results. The text implies a direct comparison rather than an adjudication process involving multiple human reviewers for interpretation.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay, where the output is typically a quantitative or qualitative (positive/negative) result generated by an instrument. The studies focus on the analytical performance of the assay itself, not on how human readers interpret images or data with or without AI assistance.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies presented are standalone performance studies of the RapidFRET Oral Fluid Assay for OPIATES. The device is intended for use in central laboratories, and the performance characteristics (precision, correlation with MS, cross-reactivity) are evaluated for the assay system itself, without an explicit "human-in-the-loop" component altering the assay's direct output. The assay provides a preliminary result, and a human professional interprets the results and applies judgment, but this is post-analysis, not part of the primary device performance evaluation described here.

7. The Type of Ground Truth Used

• Precision/Analytical Sensitivity: Spiked concentrations (known amounts of opiate in negative matrix).
• Correlation with MS Quantitation: Confirmatory analytical methods (GC/MS or LC/MS/MS) results.
• Cross-Reactivity/Analytical Specificity: Known concentrations of spiked compounds and known presence/absence of morphine.

8. The Sample Size for the Training Set

The document does not specify a separate training set for the device. As an immunoassay (competitive homogeneous immunoassay), the "training" (development and optimization) would involve biochemical and chemical engineering processes, often using various concentrations of analytes and interferents during the assay's development prior to validation. The studies described are validation and verification studies using manufactured products.

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

Since no explicit training set is described in the context of machine learning or AI, the concept of ground truth for a training set in this biological assay context refers to the controlled conditions and known spiking concentrations used during the assay's development and optimization phase. This would typically involve:

• Precisely prepared calibrators and controls: Manufactured with known concentrations of the target analyte (Morphine) to set the assay's detection limits and cutoff.
• Reference materials: Use of pure chemical standards for opiates and potential interferents.
• Known negative and positive samples: Prepared by either ensuring the absence of the analyte or by spiking known concentrations into a verified negative matrix.

These known values guide the formulation and calibration of the assay reagents and the setting of the cutoff level for discriminating positive from negative results.

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The RapidFRET Oral Fluid Assay for THC is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for Tetrahydrocannabinol at 4 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid THC Calibrator Set and RapidFRET Oral Fluid THC Control Set are intended for use only with theRapidFRET Oral Fluid Assay for THC and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, operators, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for THC is an In Vitro Diagnostic competitive immunoassay used to detect THC in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.

Here's a breakdown of the acceptance criteria and study information for the RapidFRET Oral Fluid Assay for THC, based on the provided text:

Acceptance Criteria and Device Performance

Study Information

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

• Analytical Sensitivity: 275 samples (spiked oral fluid pools) were tested per THC concentration level (0%, 25%, 50%, 75%, 100%, 125%, 150%, 175%, 200% of cutoff). Total samples for this study were 275 x 9 = 2475 measurements, though the table shows slight variations in 'N' for some percentages due to rounding or reporting.
  • Data Provenance: The oral fluid pools were "Negative oral fluid pools" spiked with THC, suggesting laboratory-prepared samples. No specific country of origin is mentioned, but typically such studies are conducted domestically. The study is prospective in nature as samples were specifically prepared and tested for this evaluation.
• Correlation with MS: 236 neat oral fluid samples from volunteers.
  • Data Provenance: "Neat oral fluid was collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for THC." This indicates prospective collection from human volunteers. No specific country of origin is mentioned.
• Cross-Reactivity: 167 different compounds were tested. The number of aliquots tested for each compound is not explicitly stated but implies multiple tests (0%, 50%, 150% THC levels).
  • Data Provenance: Laboratory-prepared spiked oral fluid pool aliquots.
• Analytical Specificity: A range of common substances and pH variations were tested. Volunteers provided oral fluid samples after using certain items.
  • Data Provenance: Laboratory-prepared spiked oral fluid pool aliquots for most common substances and pH levels. For certain items (e.g., mouthwash, chewing gum), oral fluid samples were collected prospectively from volunteers.

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

• Analytical Sensitivity, Cross-Reactivity, Analytical Specificity: The ground truth for these studies was established by the known concentration of THC (and other compounds) in spiked samples. This does not involve human experts establishing ground truth in the same way as, for example, image interpretation.
• Correlation with MS: The ground truth was established by confirmatory testing using GC/MS or LC/MS/MS. These are highly precise and sensitive analytical chemistry techniques, considered the "gold standard" for drug confirmation. The document does not specify the number or qualifications of experts running these confirmatory tests, as the methods themselves are the standard.

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

• Not applicable in the context of these analytical chemistry studies. The "adjudication" is inherent in the analytical methods used for ground truth (GC/MS or LC/MS/MS) and the pre-defined spiking concentrations. Discrepancies would be resolved by re-testing or reviewing analytical data, not by expert consensus in the typical sense.

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:

• No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an AI-based system designed to assist human readers in, for instance, image interpretation. Its performance is measured directly against analytical standards.

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

• Yes, the performance studies described are all standalone (algorithm only). The RapidFRET Oral Fluid Assay for THC operates as an automated (or semi-automated) analytical system on the RapidFRET Integrated Workstation. Its performance is evaluated based on its ability to correctly identify THC concentrations in samples, independent of human interpretation or "human-in-the-loop" interaction for result generation. Professional judgment is applied to the test result (as stated in the Intended Use), but the device itself generates a preliminary positive or negative result without human interpretation of the primary signal.

7. The type of ground truth used:

• Known concentrations: For analytical sensitivity, cross-reactivity, and analytical specificity studies, the ground truth was the known concentration of THC or other compounds in the spiked oral fluid samples.
• Confirmatory analytical methods: For the correlation study, the ground truth was established by GC/MS or LC/MS/MS analysis of the neat oral fluid samples.

8. The sample size for the training set:

• The document describes performance validation studies, not development/training of a machine learning algorithm. Therefore, there is no explicit "training set" mentioned in the context of machine learning. The device is a "homogeneous time-resolved fluorescence assay" based on competitive immunoassay principles, a well-established biochemical method, not an AI algorithm that undergoes a training phase with a dataset. Any internal development or calibration within Biophor Diagnostics would not typically be referred to as a "training set" in the context of FDA submissions for such assays.

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

• As there is no explicit "training set" for an AI algorithm, this question is not applicable. The underlying biochemical principles and internal calibration methods for the assay would rely on precisely prepared standards and controls to establish its performance characteristics.

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The RapidFRET Oral Fluid Assay for PCP is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for Phencyclidine at 10 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid PCP Calibrator Set and RapidFRET Oral Fluid PCP Control Set are intended for use only with the RapidFRET Oral Fluid Assay for PCP and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, operators, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.

The RapidFRET Oral Fluid Assay for PCP is an In Vitro Diagnostic competitive immunoassay used to detect PCP in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy. The assay is performed on the RapidFRET Integrated Workstation.

Here's a summary of the acceptance criteria and study details for the Biophor Diagnostics, Inc. RapidFRET Oral Fluid Assay for PCP, based on the provided text:

Acceptance Criteria and Device Performance

• RapidFRET POS / GC/MS POS: 119
• RapidFRET NEG / GC/MS NEG: 126
• RapidFRET POS / GC/MS NEG: 1 (Sample was 9 ng/mL PCP by GC/MS, which is below the 10 ng/mL assay cutoff)
• RapidFRET NEG / GC/MS POS: 0 |
  | Cross-Reactivity | Minimal false positive results due to structurally related or unrelated compounds, OTC/prescription medications, and drugs of abuse. | Only 4-HydroxyPCP (620 ng/mL) and PCM (310 ng/mL) were found to cross-react below 10,000 ng/mL at concentrations equivalent to the cutoff in the absence of PCP, indicating high specificity. |
  | Analytical Specificity (Interfering Substances) | No significant interference from common substances (foods, dental products, pH variations, biological components, medications). | All tested compounds and pH variations (HSA, ethanol, baking soda, whole blood, hemoglobin, hydrogen peroxide, sodium chloride, cholesterol, denture adhesive, ascorbic acid, bilirubin, IgA, IgG, IgM, mouthwash, cough syrup, cranberry juice, orange juice, toothpaste, chewing tobacco, cigarettes, chewing gum, hard candy, teeth whitening strips, cola, water, antacid, coffee, tea) at specified concentrations resulted in NEG when spiked with 5 ng/mL PCP and POS when spiked with 15 ng/mL PCP, indicating no significant interference. |

Study Details

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

   • Precision Study: The table shows totals of 279-294 samples per PCP concentration level for evaluating precision across different lots and days. This implies several hundred unique test measurements.
   • Correlation with GC/MS: n = 246 neat oral fluid samples.
   • Cross-Reactivity & Analytical Specificity: Not explicitly stated as one single test set size, but involves:
     • 175 different compounds for cross-reactivity.
     • A list of common substances and pH levels for analytical specificity.
   • Data Provenance:
     • "Neat oral fluid was collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for PCP." This indicates prospective collection from volunteers.
     • Country of origin is not explicitly stated, but the submission is to the U.S. FDA, typically implying data relevant to the U.S. market.

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

   • Not applicable/mentioned for this type of in vitro diagnostic device study. The ground truth for drug concentration is established analytically, not through expert interpretation of images or clinical findings.

3. Adjudication method for the test set:

   • Not applicable/mentioned for this type of in vitro diagnostic device study. Ground truth (PCP concentration) is determined by an objective, gold-standard chemical method (GC/MS or LC/MS/MS).

4. 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:

   • No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an in vitro diagnostic assay, not an AI-assisted diagnostic tool that relies on human readers interpreting output. The read-out and interpretation (positive/negative) is automated based on the assay's cutoff.

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

   • Yes, the performance studies described are essentially standalone for the device. The RapidFRET Oral Fluid Assay for PCP, when run on the RapidFRET Integrated Workstation, provides an automated qualitative screen (positive/negative) for PCP. Human intervention is limited to sample collection, loading, and interpreting the instrument's P/N result (with subsequent confirmation by GC/MS or LC/MS/MS). The assay itself is an "algorithm only" in the sense that it mechanically and chemically determines the result based on a pre-defined cutoff.

6. The type of ground truth used:

   • Analytical Confirmation (GC/MS): For the "Correlation with GC/MS" study, Gas Chromatography/Mass Spectrometry (GC/MS) was used as the confirmatory method to establish the true PCP concentration in the samples. The text also mentions LC/MS/MS as another specific alternate chemical method for confirmation. This represents a gold-standard analytical method.

7. The sample size for the training set:

   • Not explicitly stated for a training set in the context of machine learning. This is an immunoassay, not a machine learning algorithm that requires a distinct training set. The development of the assay, its reagents, and its cutoff would be optimized through internal research and development, which implicitly involves testing various formulations and parameters to achieve desired performance characteristics.

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

   • Not applicable in the context of a "training set" for a traditional immunoassay. The performance of the assay (e.g., sensitivity, specificity, cutoff) is established empirically through experimentation, using precisely prepared samples with known concentrations of PCP (spiked samples) and confirmed clinical samples (by GC/MS). The cutoff (10 ng/mL) is a predefined analytical threshold, not learned from a dataset.

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