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The CEDIA Buprenorphine II Assay is a homogeneous enzyme immunoassay for the qualitative and/or semiquantitative determination for the presence of buprenorphine and its metabolites in human urine at a cut-off concentration of 10 ng/ mL. The assay is intended to be used in laboratories and provides a simple and rapid analytical screening procedure to detect buprenorphine and its metabolites in human urine. The assay is designed for use with a number of clinical chemistry analyzers.

The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid chromatography/tandem mass spectrometry (LC-MS/ MS) or permitting laboratories to establish quality control procedures.

The assay provides only a preliminary analytical test result. A more specific alternative chemical must be used to obtain a confirmed analytical result. Gas chromatography/ mass spectrometry (GC/MS) or Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method.

Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.

CEDIA Buprenorphine II Calibrators:

The CEDIA Buprenorphine II calibrators and CEDIA Negative Calibrator II are intended for the calibration of the CEDIA Buprenorphine II Assay in human urine. For In Vitro Diagnostic Use Only.

CEDIA Buprenorphine II Control Set:

The CEDIA Buprenorphine II controls are used to validate the CEDIA Buprenorphine II Assay calibration in human urine. For In Vitro Diagnostic Use Only.

The assay consists of buffers (1 and 2) and lyophilized reagents (1a and 2a). The components include mouse monoclonal anti-buprenorphine antibody, recombinant microbial "enzyme donor'' - buprenorphine conjugate, "enzyme acceptor", chlorophenol red ß-Dgalactopyranoside, stabilizers and preservatives. Calibrators and controls are sold separately.

Here's a breakdown of the acceptance criteria and study information for the CEDIA Buprenorphine II Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

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The ARK™ Oxcarbazepine Metabolite Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of Oxcarbazepine Metabolite in human serum on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of Oxcarbazepine Metabolite to help ensure appropriate therapy.

The ARK™ Oxcarbazepine Metabolite Calibrator is intended for use in calibration of the ARK Oxcarbazepine Metabolite Assay.

The ARK™ Oxcarbazepine Metabolite Control is an assayed quality control material intended for use in quality control of the ARK Oxcarcarbazepine Metabolite Assay.

For prescription use only. Caution: Federal Law restricts this device to sale by or on the order of a licensed practitioner.

The ARK Oxcarbazepine Metabolite Assay is a homogeneous immunoassay based on competition between drug in the specimen and Oxcarbazepine Metabolite labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Oxcarbazepine Metabolite Assay consists of reagents R1 anti-Oxcarbazepine Metabolite polyclonal antibody with substrate and R2 Oxcarbazepine Metabolite labeled with bacterial G6PDH enzyme. The ARK Oxcarbazepine Metabolite Calibrator consists of a six-level set to calibrate the assay, and the ARK Oxcarbazepine Metabolite Control consists of a three-level set used for quality control of the assay.

The provided document describes the performance characteristics of the ARK™ Oxcarbazepine Metabolite Assay, Ark Oxcarbazepine Metabolite Calibrator, and Ark Oxcarbazepine Metabolite Control. This is a 510(k) premarket notification for a medical device (an in-vitro diagnostic assay), not an AI/ML powered device, therefore the information typically requested for AI/ML device studies (such as number of experts, adjudication methods, multi-reader multi-case studies, separate training/test sets with ground truth establishment methods for AI/ML models) are not applicable.

The acceptance criteria and performance data are detailed for several analytical validation studies.

Here's the breakdown of the requested information based on the provided document:

1. A table of acceptance criteria and the reported device performance

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

• LOQ: Not explicitly stated how many unique samples, but "mean of six (6) replicate measurements" for recovery at different enantiomer ratios.
• Recovery: Not explicitly stated how many unique samples, but "mean of six (6) replicate measurements" of Oxcarbazepine Metabolite was tabulated as a function of the enantiomer ratio.
• Linearity: Not explicitly stated how many unique samples other than a "60.0 µg/mL serum sample was prepared and dilutions were made proportionally."
• Method Comparison: 190 samples.
• Precision: 3 levels of ARK Control (N=160 each) and 3 human serum pooled specimens (N=160 each). This means for each of the 6 material types, 160 measurements were taken (quadruplicate twice a day for 20 days).
• Interfering Substances: Not explicitly stated the number of unique human serum samples, but substances were tested "in serum with known levels of Oxcarbazepine Metabolite (approximately 3 and 30 µg/mL)."
• Specificity & Drug Interference: Not explicitly stated how many unique human serum samples, but tested with spiked compounds into normal human serum with known Oxcarbazepine Metabolite levels.
• Sample Stability & Calibration Curve Stability: "supporting data" cited, but specific sample sizes are not provided within this document.

Data Provenance: The document does not specify the country of origin of the human serum samples. The studies are analytical validations performed retrospectively in a laboratory setting (e.g., Beckman Coulter AU480® automated clinical chemistry analyzer). It's not a prospective clinical trial with patient data.

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

This is an analytical chemistry assay validation, not a diagnostic imaging AI/ML model. Therefore, "experts" in the sense of physicians establishing ground truth for patient cases are not applicable. The "ground truth" for the test set (e.g., concentration of Oxcarbazepine Metabolite) is established by highly accurate reference methods such as LC-MS/MS (for method comparison) or by precise gravimetric/volumetric preparation of controls and calibrators using certified reference materials. The qualifications of the personnel performing these analytical tests are implicitly assumed to be those typical for a laboratory setting conducting such validations.

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

Not applicable. This is an analytical validation of an in-vitro diagnostic assay measuring a chemical concentration, not a study involving human readers or subjective interpretations requiring adjudication.

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 is an analytical validation of an in-vitro diagnostic assay, not an AI-assisted diagnostic device for human readers.

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

The device itself is an "algorithm only" in the sense that it is an automated chemical assay system. Its performance (quantification of Oxcarbazepine Metabolite) is assessed independently through the various analytical studies (e.g., LOQ, linearity, precision, method comparison against LC-MS/MS). Human "human-in-the-loop" performance is not a direct component of the assay's function, though human operators are involved in running the assay and interpreting the results.

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

The "ground truth" for the analytical performance studies is primarily:

• Reference Method: For method comparison, LC-MS/MS (Liquid Chromatography-Mass Spectrometry/Mass Spectrometry) is used as the reference "ground truth" method. LC-MS/MS is a highly accurate and precise analytical technique for quantifying specific compounds in complex mixtures.
• Gravimetric/Volumetric Preparation: For calibrators and controls, the "ground truth" concentrations are established by precise gravimetric addition of certified Oxcarbazepine Metabolite powder to solvents. Purity is determined by NMR and elemental analysis.

8. The sample size for the training set

This is an immunoassay, not a machine learning or AI algorithm in the traditional sense that requires a "training set" for model development. The "training" of the assay refers to its calibration. The calibrators are prepared and value-assigned as described (e.g., "Two calibrated runs are performed using the Master Calibrator. In each run, five replicates of Master Lot (reference) and Test Lot are tested as matched pairs for each calibrator level.").

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

As described above, for an immunoassay, the "training set" is the calibrator set. The ground truth for the calibrators is established through:

• Traceability to certified powder: The calibrators are traceable to certified Oxcarbazepine Metabolite powder. "The purity of Oxcarbazepine Metabolite in the certified raw material is determined by NMR and elemental analysis as performed by the supplier of the certified powder."
• Gravimetric Addition: "Bulk solutions of the ARK Oxcarbazepine Metabolite Calibrator are prepared volumetrically using a stock solution prepared by gravimetric addition of powder to solvent."
• Value Assignment: "Testing is performed with the ARK Oxcarbazepine Metabolite Assay on the Beckman Coulter AU480® automated analyzer. Two calibrated runs are performed using the Master Calibrator. In each run, five replicates of Master Lot (reference) and Test Lot are tested as matched pairs for each calibrator level. Mean values for ten replicates are calculated." This process ensures consistency and accuracy against a master reference.

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The Detectabuse® Liquid control is an In Vitro Diagnostic (IVD) device, for prescription use only, that is intended for use as quality control urine to monitor the precision of laboratory urine toxicology testing procedures for the analytes listed in the package insert.

The Detectabuse® controls are designed to provide an estimation of the precision of a device test system, and to detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects, at levels established by SAMHSA, CAP/AACC, many state programs and device manufacturers QC requirements. The Detectabuse® control urines are compatible with all quantitative and qualitative drug detection procedures which are sufficiently sensitive to detect the control constituents. They should be treated as any "unknown" specimen while following the specific protocol of the assay being used. This product is intended to be used under the supervision of health care professionals as an integral part of good laboratory practices.

Each bottle contains stabilized human based urine. Multi-constituent and single constituent positive control urines have been gravimetrically spiked with authentic reference drug standards and/or appropriate metabolites. Negative control urines are certified negative by combination of immunoassay, GC/MS and/or LC/MS for the constituents listed on our target sheets. The products contain less than 1% sodium azide as a preservative. For assays sensitive to sodium azide such as ELISA we substitute a proprietary preservative approved by the manufacturers and DEA.

This document describes the performance characteristics and acceptance criteria for the Detectabuse® Liquid Control Urine device. This device is an In Vitro Diagnostic (IVD) intended for use as quality control urine to monitor the precision of laboratory urine toxicology testing procedures.

The study that proves the device meets the acceptance criteria is primarily an analytical performance study focusing on stability and traceability.

1. Table of Acceptance Criteria and Reported Device Performance

| Evaluation Parameter | Acceptance Criteria | Reported Device Performance |
|---------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------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| Open Bottle Stability at 2-8°C | 31 days | Data support the 31-day open bottle stability at 2-8°C for all analytes. All analytes passed specifications, Positive controls tested positive, and Negative controls tested negative. |
| Closed Bottle Stability - Product Shelf Life (2-8°C) | Storage with Oxazepam expected to be negatively affected if >6 months. Other drugs within ±15% of target until expiration. | At 1 year, Oxazepam dropped 15-22%. At 3 years, Oxazepam dropped to 25%. Other drugs were within acceptable criteria of +/-15% from target until expiration date. Recommendation: Do not store Oxazepam-containing controls refrigerated for more than six months. |
| Closed Bottle Stability - Product Shelf Life (-10°C to -20°C) | Up to 4 years. Values within ±15% of target or original test value. | Multiple studies with various lots showed all drugs were stable within 15% of target or original test value between 3 and 4 years of frozen storage. |
| Room Temperature (open vial) Stability - Product Shelf Life (18°C to 21°C) | 31 days. Values within ±18% of target or original test value. | All drugs tested for 31 days were within 18% of target value or original test value. This supports stability during shipping or brief periods of customer error. |
| Value Assignment Criteria | Initially: ±5% agreement (acceptable to ±10% for certain difficult-to-test drugs). For Stat-Skreen® controls, positive controls must test positive and negative controls test negative. Final testing at shelf life: ±10% of target (acceptable to ±15% for certain stability-prone constituents like Oxazepam). | Initial production batch samples sent to 4-5 certified laboratories (at least 3 proficient for specific constituents). If a testing laboratory does not report within 10% of target, the sample is repeated. Once acceptable convergence of values is achieved, the lot is released. Stat-Skreen® controls are also tested on handheld devices against the criteria. Final testing at shelf life (GC/MS or LC/MS) aims for ±10% of target but accepts up to ±15% for specific constituents like Oxazepam. |

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

The document does not explicitly state a numerical sample size for "test sets" in the context of typical algorithm validation (i.e., a distinct set used for performance evaluation after training). Instead, the performance evaluations are described for stability studies and value assignment verification.

• Stability Studies: "Multiple bottles of a single lot" were pulled from beginning, middle, and end of production. "Several lots" of controls were selected for the room temperature study. "Multiple studies were conducted using various different lots."
• Value Assignment: "An initial production batch is sampled as described in the protocol and single or multiple samples (depending on our past experience with the constituent(s), are ordinarily sent out to 4 or 5 certified laboratories..."
• Data Provenance: The data is generated through laboratory testing of the control materials. The document implies a prospective data collection for stability studies (testing at initial, then at intervals) and for value assignment. The "certified independent laboratories" or "SAMHSA licensed laboratories or CAP inspected and certified" are likely located in the USA, given the FDA submission context.

3. Number of Experts and Qualifications for Ground Truth

• Ground Truth Establishment for Value Assignment: "Certified Independent laboratories" test by either GC/MS, LC/MS, or Immunoassay screening. For initial value assignment, "4 or 5 certified laboratories" (or at least 3 for less common constituents) perform testing. The qualifications for personnel performing these tests at "certified" or "SAMHSA licensed" or "CAP inspected and certified" labs are implied to be high, but specific expert qualifications (e.g., "radiologist with 10 years of experience") are not detailed. The expertise is in the analytical methods (GC/MS, LC/MS, immunoassay).

4. Adjudication Method

The adjudication method for value assignment resembles a form of consensus or agreement-based approach.

• "A minimum of 3 data points are collected for each assay."
• "Data collected from at least two test sites, testing performed within 1 week of receipt of test samples."
• "Our target acceptance criteria Is ±5% of the target value, but if we cannot get ± 5% agreement from our testing laboratories we will accept ± 10%... If a testing laboratory does not report within 10% of target we ask that the sample be repeated. Once we have an acceptable convergence of values from all of the testing laboratories the lot is released."

This suggests repeated testing and comparison among multiple labs with defined acceptance thresholds for agreement, rather than a formal 2+1 or 3+1 adjudication by individual experts in the traditional sense for image interpretation.

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

• No MRMC comparative effectiveness study was done. This device is a quality control material, not an AI diagnostic tool intended to assist human readers. Therefore, the concept of improving human reader performance with AI assistance is not applicable.

6. Standalone (Algorithm Only) Performance Study

• A standalone performance study was done in the sense that the device, as a quality control material, is evaluated on its own analytical properties (stability, assigned values, precision monitoring capability) using laboratory instruments. There isn't an "algorithm" in the typical AI sense; the "device" itself is the control material. Its performance is measured by how precisely and accurately analytical instruments can detect the specified concentrations within the control.

7. Type of Ground Truth Used

The ground truth used for this device is based on analytical quantification methods and certified reference standards:

• Gravimetric spiking with authentic reference drug standards and/or appropriate metabolites.
• Purity determination using analytical tools including GC/MS, LC/MS, and NMR.
• Balances calibrated with weights traceable to National Institute of Standards and Technology (NIST).
• Testing by SAMHSA or CAP certified independent laboratories using GC/MS, LC/MS, or Immunoassay screening.
• Negative control urines are certified negative by combination of immunoassay, GC/MS and/or LC/MS.

This constitutes a highly rigorous, metrologically traceable analytical ground truth.

8. Sample Size for the Training Set

The concept of a "training set" as understood in machine learning is not applicable here. This device is a chemical control material, not an AI algorithm that learns from data. The manufacturing and validation processes involve:

• Reference standards and gravimetric preparation: These form the basis for the intended concentrations.
• Initial production batches: These are the manufacturing lots that undergo value assignment and stability testing as described above.

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

As noted above, there is no "training set" in the AI sense. The "ground truth" (i.e., the known and verified concentrations of analytes in the control material) is established through:

• Precise gravimetric preparation: Spiking authentic reference drug standards (traceable to NIST) into the human-based urine matrix at known concentrations.
• Purity verification of reference standards: Using advanced analytical techniques such as GC/MS, LC/MS, and NMR.
• Verification by multiple independent certified laboratories: The value assignment process, involving multiple labs and stringent acceptance criteria, serves to confirm the prepared concentrations with high confidence.

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Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay is intended for use in laboratories for the qualitative analyses of buprenorphine in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers.

The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as LC/MS or Permitting laboratories to establish quality control procedures.

The Emit® II Plus Buprenorphine Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/ MS) or LC/MS are the preferred confirmatory methods. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

Emit® II Plus Specialty Drug Calibrator/Control Level 1, Emit® II Plus Specialty Drug Calibrator/Control Level 2, Emit® II Plus Specialty Drug Calibrator/Control Level 3, Emit® II Plus Specialty Drug Calibrator/Control Level 4

The Emit® II Plus Specialty Drug Calibrators/Controls are used in the calibration of the Emit® II Plus Buprenorphine Assay. These products may also be used as quality control materials based on the Buprenorphine Assay cutoff.

Emit® II Plus Specialty Drug Control Negative and Emit® II Plus Specialty Drug Control Positive

The Emit® II Plus Specialty Drug Control Negative and Control Positive are for use with the Emit® II Plus Buprenorphine Assay.

The Emit® II Plus Buprenorphine assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay, used for the detection of Buprenorphine in human urine, utilizes a two-reagent system. The Antibody/Substrate Reagent 1 is a liquid ready-to-use product comprised of mouse monoclonal antibodies to buprenorphine, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in a diluent containing bovine serum albumin (BSA), preservatives and stabilizers. The Enzyme Reagent 2 is a liguid. ready-to-use product containing norbuprenorphine labeled bacterial recombinant glucose-6 phosphate dehydrogenase (rG6PDH) in a diluent containing bovine serum albumin (BSA), Hepes buffer, preservatives and stabilizers.

The assay kit consists of Reagent 1 and Reagent 2 in plastic containers and is available in three sizes: large kit (1L), small kit (115 mL), and 28 mL Emit® II Plus assays are designed for use with a number of chemistry analyzers.

The Emit® II Plus Buprenorphine assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result.

Emit® II Plus Specialty Drug Calibrators / Controls are in-vitro diagnostic products used in the calibration of the Emit® II Plus Buprenorphine assay. These products may also be used as quality control materials based on the Buprenorphine Assay cutoff. The matrix is pooled, drug-free, human urine based product containing buprenorphine, preservatives and surfactants. Each level of calibrator is packaged and sold separately, 1 plastic bottle per box, 10 mL in a 15 mL bottle. Values are nominal and are verified with urine based buprenorphine anchor pool and adjusted if needed. The anchor pool levels are verified by LC/MS/MS and are within 10% of nominal drug concentration for levels 2.5 and 5.0 ng/mL and within 5 % of nominal concentrations for levels 15 and 25 ng/mL.

Emit® II Plus Specialty Drug Control Negative and Emit® II Plus Specialty Drug Control Positive are in-vitro diagnostic products are for use with the Emit® II Plus Buprenorphine assay. The matrix is pooled, drug-free, human urine based product containing buprenorphine, preservatives and surfactants. The Control Negative and Control Positive are packaged separately in 15 mL plastic vials with a 10 mL fill per vial. Values are nominal and are verified with urine based buprenorphine anchor pool and adjusted if needed. Anchor pool levels are verified by LC/MS/MS.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

Device: Emit® II Plus Buprenorphine Assay, Emit® II Plus Specialty Drug Calibrator/Control Level 1-4, Emit® II Plus Specialty Drug Control Negative/Positive.

Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numbered or bulleted points in the provided document. However, based on the performance data presented, we can infer the criteria that the device aimed to meet for substantial equivalence. The document primarily focuses on demonstrating performance against expected standards for an in vitro diagnostic device for drug screening, particularly a qualitative and semi-quantitative assay.

Here's a table summarizing the inferred acceptance criteria and the device's performance:

• Consistent classification (Negative/Positive) for concentrations significantly below/above cutoff.
• Acceptable level of concordant/discordant results near the cutoff for both qualitative and semi-quantitative modes. | Precision: Qualitative Analysis (5 ng/mL cutoff)
• 0, 2.5, 3, 3.75 ng/mL (below cutoff): 80 Negative out of 80 results (100% agreement).
• 5 ng/mL (cutoff): 25 Negative / 55 Positive (68.75% positive, 31.25% negative). This indicates some variability at the exact cutoff, which is typical for immunoassays.
• 6.25, 7, 7.5, 10 ng/mL (above cutoff): 80 Positive out of 80 results (100% agreement).
• Additional Precision Study:
  • 1.25 ng/mL (-75% cutoff): 80 Negative out of 80 results (100% agreement).
  • 8.75 ng/mL (+75% cutoff): 80 Positive out of 80 results (100% agreement).
    Overall, good precision away from the cutoff, expected variability at the cutoff. |
    | Precision (Semi-quantitative Analysis) - Agreement near cutoff
• Consistent classification (Negative/Positive) and semi-quantitative results for concentrations significantly below/above cutoff. | Precision: Semi-quantitative Analysis (5 ng/mL cutoff)
• 0, 2.5, 3, 3.75 ng/mL (below cutoff): 80 Negative out of 80 results (100% agreement).
• 5 ng/mL (cutoff): 25 Negative / 55 Positive (68.75% positive, 31.25% negative).
• 6.25, 7, 7.5, 10 ng/mL (above cutoff): 80 Positive out of 80 results (100% agreement).
• Additional Precision Study:
  • 1.25 ng/mL (-75% cutoff): 80 Negative out of 80 results (100% agreement).
  • 8.75 ng/mL (+75% cutoff): 80 Positive out of 80 results (100% agreement).
    Results mirror qualitative analysis, demonstrating consistent semi-quantitative performance. |
    | Specificity and Cross-reactivity - Buprenorphine Metabolites
• Appropriate cross-reactivity with buprenorphine and its primary active metabolite (norbuprenorphine).
• Low to no cross-reactivity with inactive glucuronide metabolites. | Buprenorphine Metabolite Recovery
• Buprenorphine (5 ng/mL): 103.2% recovery (5.2 ng/mL).
• Norbuprenorphine (5 ng/mL): 92.6% recovery (4.6 ng/mL).
• Buprenorphine Glucuronide (1000 ng/mL): 0.1% cross-reactivity (0.9 ng/mL).
• Norbuprenorphine Glucuronide (1000 ng/mL): 0.1% cross-reactivity (1.2 ng/mL).
  Demonstrates good detection of buprenorphine and norbuprenorphine, minimal interference from inactive glucuronide metabolites. |
  | Specificity and Cross-reactivity - Structurally Related Compounds
• No significant false positives from a panel of common opioids and other structurally related compounds at high concentrations. | Cross-reactivity with Structurally Related Compounds
• Over 20 common opioids and related compounds (e.g., 6-acetylcodeine, codeine, heroin, morphine, oxycodone) were tested at 100,000 ng/mL.
• All tested compounds showed "Negative" qualitative results and "

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The DRI® Hydrocodone Assay is intended for the qualitative and semi-quantitative detection and estimation of Hydrocodone and its metabolites in human urine at a cutoff of 300 ng/mL. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of specimen for confirmatory method such as LC-MS/MS or GC-MS and permitting laboratories to establish quality control measures.

This assay provides a preliminary analytical test result. A more specific alternative chemical method must be used in order to confirm an analytical result. Gas chromatography/mass spectrometry (GC/MS) and Liquid Chromatography/ tandem mass spectrometry (LC-MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

The DRI® Hydrocodone Assay Calibrators are intended for the DRI® Hydrocodone Assay. For In Vitro Diagnostic Use Only.

The DRI® Hydrocodone Controls are unassayed quality control material intended for use in the DRI Hydrocodone Assay to detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects. For In Vitro Diagnostics Use Only

The DRI® Hydrocodone Assay is supplied as a liquid ready-to-use homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect Hydrocodone and its metabolites without any significant cross-reactivity to other opiate compounds. The assay is based on competition between a drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) and free drug from the urine sample, for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample, the specific antibody binds the drug labeled with G6PDH and causes a decrease in enzyme activity. In the presence of free drug, the free drug occupies the antibody binding sites, allowing the drug bound G6PDH to interact with the substrate, resulting in enzyme activity. This phenomenon creates a direct relationship between the drug concentration in urine and enzyme activity. The enzyme activity is determined spectrophotometrically at 340 nm by measuring the conversion of nicotinamide adenine dinucleotide (NAD) to NADH.

The DRI® Hydrocodone Assay is a kit comprised of two reagents, Reagent A and Reagent E, which are bottled separately but sold together within the same kit.

The Reagent A solution contains: mouse monoclonal anti-hydrocodone antibody, glucose-6phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide (≤0.09%) as a preservative). The Reagent E solution contains: glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with Sodium Azide (≤0.09%) as preservative.

The DRI® Hydrocodone Enzyme Immunoassay calibrators designated for use at the 300 ng/mL cutoff contain 0 (negative), 100, 300, 500, and 1,000 ng/mL of hydrocodone in human urine matrix with sodium azide (≤0.09%) as preservative. The controls are provided at a concentration of 225 and 375 ng/mL. The calibrators are sold separately and the two controls are sold as a kit.

Here's a breakdown of the acceptance criteria and study information for the DRI® Hydrocodone Assay, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

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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 Immunalysis EDDP Specific Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with cutoffs of 100 ng/mL, 300n g/mL and 1000 ng/mL. The assay is intended for use in laboratories for the qualitative and semiquantitative analysis of EDDP in human urine with automated clinical chemistry analyzers. This assay is calibrated against EDDP. This in-vitro 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 GC-MS or permitting laboratories to establish quality control procedures.

The Immunalysis EDDP Specific Urine Enzyme Immunoassay Kit 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 drug of abuse test result, particularly when preliminary positive results are used.

Immunalysis EDDP Urine Calibrators
The Immunalysis EDDP Urine Calibrators are used as calibrators in the Immunalysis EDDP Specific Urine Enzyme Immunoassay for the qualitative and semi-quantitative determination of EDDP in urine on automated clinical chemistry analyzers.

Immunalysis EDDP Urine Control Sets
The Immunalysis EDDP Urine Control Sets are used as control materials in Immunalysis EDDP Specific Urine Enzyme Immunoassay.

The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. 1. The antibody/ substrate reagent includes recombinant fab antibodies to EDDP. glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes EDDP derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with Sodium Azide as a preservative.
2. All of the Immunalysis EDDP Calibrators and Controls are liquid and ready to use. These calibrators and controls do not have any especially unique technical characteristics. Each contains a known concentration of a specific drug analyte as a mixture.

The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators, as well as the LOW Control 1, HIGH Control 1, LOW Control 2 and HIGH Control 2, and LOW Control 3 and HIGH Control 3 are prepared by spiking known concentrations of EDDP into the negative calibrator matrix. These five calibrators and six controls are sold as individual bottles.

The provided document describes the Immunalysis EDDP Specific Urine Enzyme Immunoassay, along with its calibrators and control sets, and the studies conducted to demonstrate its substantial equivalence to a predicate device.

Here's an analysis based on your requested information:

1. Table of Acceptance Criteria and Reported Device Performance

For qualitative results, the acceptance criterion generally implies a high level of agreement with the confirmatory method, especially around the cutoff concentrations. For semi-quantitative results, similar high agreement is expected. Precision studies demonstrate the device's ability to consistently produce the same value. Specificity and interference studies aim to show that the device accurately identifies EDDP without significant false positives or negatives due to other compounds or physiological conditions.

Below is a table summarizing the reported device performance for the Qualitative and Semi-Quantitative Method Comparison studies, which are key to assessing acceptance criteria:

Table: Acceptance Criteria and Reported Device Performance (Method Comparison)

For Precision/Cutoff Characterization, the acceptance criteria are generally that samples below the cutoff are consistently negative and samples above the cutoff are consistently positive. Samples at the cutoff are expected to show a mix of positive and negative results, indicating the cutoff acts as a boundary. The device demonstrated this behavior across all cutoffs (100, 300, 1000 ng/mL) for both qualitative and semi-quantitative analysis. For example, at the 100 ng/mL cutoff, concentrations below 100 ng/mL yielded 80 negative results out of 80 determinations, while concentrations above 100 ng/mL yielded 80 positive results out of 80 determinations. At the 100 ng/mL cutoff itself, there were a mix of positive and negative results as expected (e.g., 43 Negative / 37 Positive for qualitative, 10 Negative / 70 Positive for semi-quantitative).

The specificity and interference studies showed that many structurally non-similar compounds up to high concentrations did not interfere with the assay. Some structurally similar compounds (e.g., Methadone, Chlorpromazine, Methylphenidate, Diphenhydramine, (±)-alpha methadol) did show cross-reactivity at high concentrations, and these are noted in the labeling. Boric Acid was identified as an interferent and limitations added to the labeling. pH and Specific Gravity within tested ranges did not interfere.

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

• Sample Size (Method Comparison):
  • For the 100 ng/mL cutoff: 80 unique clinical urine samples (40 positive by LC/MS and 40 negative by LC/MS). (Table 31)
  • For the 300 ng/mL cutoff: 80 unique clinical urine samples (40 positive by LC/MS and 40 negative by LC/MS). (Table 34)
  • For the 1000 ng/mL cutoff: 80 unique clinical urine samples (40 positive by LC/MS and 40 negative by LC/MS). (Table 36)
• Sample Size (Precision/Cutoff Characterization): For each cutoff (100, 300, 1000 ng/mL) and each concentration level relative to the cutoff (e.g., -100%, -75%, -50%, -25%, Cutoff, +25%, +50%, +75%, +100%), there were 80 determinations (20 days, 2 runs per day, in duplicate). This results in 9 concentration levels * 80 determinations = 720 determinations per cutoff. This was done for qualitative and semi-quantitative modes.
• Data Provenance: The Method Comparison study used "Unaltered, anonymous and discarded clinical urine samples obtained from clinical testing laboratories." This indicates the data is retrospective and its country of origin is not explicitly stated but is implicitly from the US given the FDA submission. The other studies (Precision, Specificity, Interference, Linearity/Recovery) appear to use spiked or prepared samples, not directly from patients.

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 experts to establish ground truth for the test set.
• Instead, the ground truth for the method comparison study was established using a "more specific alternate chemical method," specifically Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS). These are analytical laboratory techniques, not human expert interpretation.

4. Adjudication Method for the Test Set

• Since the ground truth was established by LC/MS, there was no human adjudication process described for the test set results. The device's results were directly compared to the LC/MS confirmation.

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 MRMC comparative effectiveness study was done. This device is an in-vitro diagnostic assay (an enzyme immunoassay) for the detection of EDDP in urine, not an AI-based image analysis or diagnostic tool that involves human readers interpreting results with or without AI assistance.

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

• Yes, the performance data presented is for the device operating in a standalone manner. The "Test Device" results were compared directly against the LC/MS confirmation. The assay is performed on automated clinical chemistry analyzers.

7. The Type of Ground Truth Used

• The primary ground truth used for performance verification (Method Comparison) was LC/MS (Liquid Chromatography/Tandem Mass Spectrometry) Confirmation. This is a highly accurate chemical analytical method considered the gold standard for drug confirmation.
• For other studies (Precision, Specificity, Interference, Linearity/Recovery), the ground truth was based on known concentrations of EDDP or other compounds in prepared urine matrices.

8. The Sample Size for the Training Set

• The document does not describe a "training set" in the context of machine learning or AI. This is a traditional immunoassay device. The assay development process involves optimization, but there isn't a "training set" in the way it's defined for AI/ML models. For traditional assays, development involves iterative testing and refinement of reagents and protocols using various samples, but this is distinct from training an algorithm.

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

• As mentioned above, there is no explicit "training set" in the AI/ML sense. The "ground truth" for the calibrators and controls used in the assay itself is established by spiking known concentrations of EDDP into a synthetic urine matrix and verifying these concentrations through mass spectrometry.

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The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a dual cutoff of 150ng/mL and 300ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Benzoylecgonine in human urine with automated clinical chemistry analyzers. This assay is calibrated against Benzoylecgonine. This in-vitro 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 GC-MS or permitting laboratories to establish quality control procedures.

The Immunalysis Benzoylecgonine Urine Enzyme Immunoassay Kit 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 / Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

Immunalysis Benzoylecgonine Urine Calibrators

The Immunalysis Benzoylecgonine Urine Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine. The calbrators are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers.

Immunalysis Benzoylecgonine Urine Control Set

The Immunalysis Benzoylecgonine Urine Control Set is intended for in vitro diagnostic use to monitor the performance of assays for the analyte currently listed in the package insert: Benzoylecgonine. The controls are designed for prescription use with homogenous enzyme immunoassays on automated clinical chemistry analyzers

1. The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes polyclonal sheep antibodies to Benzoylecgonine, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Benzoylecgonine derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with Sodium Azide as a preservative.
2. All of the Immunalysis Benzoylecgonine Urine Calibrators and Controls are liquid and ready to use. Each contains a known concentration of a specific drug analyte as a mixture.

The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators, as well as the LOW Control 1, HIGH Control 1, LOW Control 2 and HIGH Control 2 are prepared by spiking known concentrations of benzoylecgonine into the negative calibrator matrix. These five calibrators and four controls are sold as individual bottles.

The provided document describes the acceptance criteria and the study results for the Immunalysis Benzoylecgonine Urine Enzyme Immunoassay.

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" in a single table with performance targets. However, the performance studies implicitly define the criteria by demonstrating acceptable results across various tests. For the purpose of this response, I've inferred the acceptance criteria based on the reported "Result" and "Interference?" columns, where "No" interference or expected qualitative results (Positive/Negative) for varying concentrations are considered acceptable.

Qualitative Analysis (150ng/mL cutoff):

Qualitative Analysis (300ng/mL cutoff):

Semi-Quantitative Analysis (150ng/mL cutoff):

Semi-Quantitative Analysis (300ng/mL cutoff):

Specificity and Cross-Reactivity (150ng/mL cutoff - Qualitative & Semi-Quantitative): All listed "Structurally Related Compounds" except Ecgonine Methyl Ester, Cocaethylene, and Norcocaine should show positive results at the tested concentration, demonstrating cross-reactivity where expected, and negative otherwise. This is shown as "POS" or "NEG" in the tables, with corresponding Cross-Reactivity (%).

Specificity and Cross-Reactivity (300ng/mL cutoff - Qualitative & Semi-Quantitative): All listed "Structurally Related Compounds" except Benzoylecgonine and m-Hydroxybenzoylecgonine should show negative results at the tested concentration. This is shown as "POS" or "NEG" in the tables, with corresponding Cross-Reactivity (%).

Interference Study (Structurally Non-Similar Compounds, Endogenous Compounds, pH, Specific Gravity):
For all tested compounds and parameters (pH range 3.0-11.0, Specific Gravity range 1.000-1.030) and both cutoffs, the reported device performance indicates "No" interference, which is the implicit acceptance criterion, except for Boric Acid.

Linearity/Recovery:
The reported recovery percentages range from 91.2% to 108.6%, indicating generally good linearity and recovery. The implicit acceptance criterion would be that recovery falls within a generally accepted range (e.g., +/- 20% of expected, or tighter), which the data appears to satisfy for most points.

Method Comparison (Qualitative & Semi-Quantitative for both cutoffs):
The acceptance criterion is high agreement with LC/MS confirmation.
For 150ng/mL cutoff:

• Qualitative Positive Agreement: 98% (1 sample with 124ng/mL Benzoylecgonine by LC-MS/MS was positive by device but had a concentration below the 150ng/mL cutoff, leading to 1 false positive out of 40 true positives)
• Qualitative Negative Agreement: 100%
• Semi-Quantitative Positive Agreement: 98%
• Semi-Quantitative Negative Agreement: 100%

For 300ng/mL cutoff:

• Qualitative Positive Agreement: 100%
• Qualitative Negative Agreement: 100%
• Semi-Quantitative Positive Agreement: 100%
• Semi-Quantitative Negative Agreement: 100%

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

• Precision/Cutoff Characterization/Reproducibility: 80 determinations for each concentration level for both qualitative and semi-quantitative analyses, at both 150ng/mL and 300ng/mL cutoffs. This means a total of 80x9=720 determinations for each cutoff in qualitative mode, and 80x9=720 for semi-quantitative total determinations. The samples were generated specifically for the study at defined concentrations; their provenance is thus "prepared samples."
• Specificity and Cross-Reactivity: Structurally similar compounds were spiked into drug-free urine.
• Interference: Structurally non-similar compounds, endogenous compounds, effect of pH, and effect of specific gravity were evaluated by spiking potential interferents into drug-free urine containing the target analyte at ±25% of the cutoff.
• Linearity/Recovery: A drug-free urine pool was spiked with a high concentration of the target analyte, and serial dilutions were made.
• Method Comparison: Unaltered, anonymous, and discarded clinical urine samples were obtained from clinical testing laboratories. The number of samples for the method comparison was 40 positive and 40 negative for each cutoff (150ng/mL and 300ng/mL) based on LC/MS confirmation, for a total of 80 unique samples that were then compared against the device for qualitative and semi-quantitative results. The provenance is retrospective clinical samples.

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

The document does not specify the number of experts or their qualifications for establishing ground truth. The ground truth for the test set (Method Comparison) was established using Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography / Mass Spectrometry (LC/MS), which are considered preferred confirmatory methods, rather than human expert interpretation. For other studies (Precision, Specificity, Interference, Linearity), the ground truth was established by preparing samples with known concentrations of analytes.

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

Not applicable, as the ground truth was established by objective analytical methods (GC-MS/LC-MS) or sample preparation with known concentrations, not by subjective human expert adjudication.

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 immunoassay for chemical analysis, not an AI-assisted diagnostic imaging device requiring human-in-the-loop performance evaluation.

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

Yes, the performance studies (Precision, Specificity, Interference, Linearity, Method Comparison) represent the standalone performance of the Immunalysis Benzoylecgonine Urine Enzyme Immunoassay device. The device's results are generated by automated clinical chemistry analyzers (Beckman Coulter AU 400e) without human interpretation in the determination of the qualitative or semi-quantitative result. The document emphasizes that the EIA provides a "preliminary analytical test result" and "A more specific alternate chemical method must be used in order to obtain a confirmed analytical result."

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

• Precision/Cutoff Characterization/Reproducibility, Specificity/Cross-Reactivity, Interference, Linearity/Recovery: Known concentrations of Benzoylecgonine or other compounds spiked into drug-free urine were used as ground truth.
• Method Comparison: LC/MS (Liquid Chromatography/Mass Spectrometry) confirmation was used as the ground truth for clinical urine samples.

8. The sample size for the training set

This is not applicable as the device is a chemical immunoassay kit, not a machine learning or AI algorithm that requires a training set in that context. The "training" would refer to the development and optimization of the assay reagents and conditions.

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

Not applicable for the same reason as point 8. The development process would involve analytical testing and optimization against known standards and characterized samples to establish the assay's performance characteristics.

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The Immunalysis Cannabinoids Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay with a cutoff of 50ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of Cannabinoids in human urine with automated clinical chemistry analyzers. This assay is calibrated against 11-nor-9-carboxy-A9-THC (cTHC). This in-vitro 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 GC-MS or permitting laboratories to establish quality control procedures.

The Immunalysis Cannabinoids Urine Enzyme Immunoassay Kit 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/Mass Spectrometry (LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

Immunalysis cTHC Urine Control Set: The Immunalysis cTHC Urine Control Set is used as control materials in the Immunalysis Cannabinoids Urine Enzyme Immunoassay.

Immunalysis cTHC Urine Calibrators: The Immunalysis cTHC Urine Calibrators are used as calibrators in the Immunalysis Cannabinoids Urine Enzyme Immunoassay for the qualitative and semi-quantitative determination of Cannabinoids in urine on automated clinical chemistry analyzers.

The assay consists of antibody/ substrate reagent and enzyme conjugate reagent. The antibody/ substrate reagent includes monoclonal and polyclonal antibodies to Cannabinoids, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide as a preservative. The enzyme conjugate reagent includes Cannabinoids derivative labeled with glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with Sodium Azide as a preservative. Calibrators and controls are sold separately. Reagents are liquid, ready to use.

All of the Immunalysis cTHC Urine Calibrators and Controls are liquid and ready to use. Each contains a known concentration of a specific drug analyte as a mixture.

The negative calibrator is a processed, drug-free synthetic urine matrix with sodium azide as a preservative. The Level 1, 2, 3 and 4 calibrators, as well as the LOW Control and HIGH Control are prepared by spiking known concentrations of 11-nor-9-carboxy-Δ'-THC (cTHC) into the negative calibrator matrix. The negative calibrator, Level 1 calibrator, Level 2 calibrator, Level 3 calibrator, Level 4 calibrator and two controls are sold as individual bottles.

The document describes the Immunalysis Cannabinoids Urine Enzyme Immunoassay, its calibrators, and control set, which are intended for qualitative and semi-quantitative analysis of Cannabinoids in human urine with a cutoff of 50ng/mL. The study evaluates the performance of the device against this cutoff.

Here's an analysis of the provided information concerning acceptance criteria and the study that proves the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical targets in the document for each test. However, the studies demonstrate the device's performance relative to its intended use and consistency around the 50 ng/mL cutoff. The implicit acceptance criteria appear to be:

• Qualitative Analysis: Accurate classification of samples as negative below the -25% cutoff and positive above the +25% cutoff, with consistent results at the cutoff.
• Semi-Qualitative Analysis: Similar to qualitative, with consistent results around the cutoff.
• Specificity and Cross-Reactivity: Structurally similar compounds should show expected cross-reactivity, and structurally dissimilar compounds should not interfere.
• Interference: Various endogenous compounds, pH levels, and specific gravity should not cause interference.
• Recovery: Expected concentrations should be recovered within an acceptable range.
• Method Comparison: High agreement with LC/MS confirmation for both qualitative and semi-quantitative modes.
• Calibration and Control Performance: Traceability and stability of calibrators and controls within specifications.

• Samples at 0, 12.5, 25, 37.5 ng/ml (cutoffs -100% to -25%) showed 80 Negative results (100% agreement).
• Samples at 50 ng/ml (cutoff) showed 40 Negative/40 Positive results.
• Samples at 62.5, 75, 87.5, 100 ng/ml (cutoffs +25% to +100%) showed 80 Positive results (100% agreement). |
  | Semi-Quantitative Analysis (50ng/mL cutoff)| Similar to qualitative analysis. | Table 3:
• Samples at 0, 12.5, 25, 37.5 ng/ml showed 80 Negative results (100% agreement).
• Samples at 50 ng/ml (cutoff) showed 38 Negative/42 Positive results.
• Samples at 62.5, 75, 87.5, 100 ng/ml showed 80 Positive results (100% agreement). |
  | Specificity & Cross-Reactivity (Structurally Related Compounds - Qualitative)| Expected varying cross-reactivity for structurally similar compounds at specific concentrations. | Table 4:
• 11-nor-9-carboxy-Δ9-THC (50ng/mL): 100% Cross-Reactivity (Positive)
• (±) 11-Hydroxy-Δ9-THC (100ng/mL): 50.0% Cross-Reactivity (Positive)
• 11-nor-Δ8-carboxy-THC (40ng/mL): 125.0% Cross-Reactivity (Positive)
• Cannabinol (75ng/mL): 66.7% Cross-Reactivity (Positive)
• Cannabidiol (1,000,000ng/mL):

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