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AC/AD Linearity Verifiers are intended to be used to verify the calibration, linear operating range and reportable range (linearity) of methods used to determine the concentration of therapeutic drugs.

AC/AD Linearity Verifiers should be used any time it is necessary to confirm the proper callbration and linear operating range of TDM methods and instruments. Quality control/verification requirements should be determined in conformance with local, state and/or Federal regulations or accreditation requirements

medical device intended for use with automated and manual methods monitoring selected therapeutic drugs (TDM). AC/AD Linearity Verifiers is a five level, multiconstituent set of calibrators made in human serum and used to confirm the proper calibration, linear operating range and reportable range (linearity) of TDM methods. The "AC/AD" designation derives from AntiConvulsant, antiAnxiety and other Qrugs. AC/AD Linearity Verifiers contains concentrations of analytes extending over a wide analytical range. Level 1 is a zero level 5 has a concentration near the upper limit of instruments. Levels 1, 2, 3, and 4 are related by linear dilution. When assayed like patient samples, the verifiers assist in determination of calibration and linear operating range (linearity) of methods for the analytes included.

This 510(k) submission (K982217) describes the AC/AD^TM Linearity Verifiers, a device used to verify the calibration, linear operating range, and reportable range for therapeutic drug monitoring (TDM) methods. The submission focuses on demonstrating substantial equivalence to a predicate device, the ABC^TM Linearity Verifiers, rather than presenting a study against a pre-defined set of acceptance criteria for a novel device. Therefore, some of the requested information, particularly regarding specific numerical acceptance criteria and a detailed study design meeting such criteria, is not present in this document in the typical format for performance studies.

However, based on the provided text, we can infer some aspects and extract relevant information.

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly list numerical "acceptance criteria" for the AC/AD Linearity Verifiers in the way one might see for a diagnostic test. Instead, the performance assessment is geared towards demonstrating functional equivalence to the predicate device and confirming the "desired functionality."

Inference: The implicit acceptance criterion for the AC/AD Linearity Verifiers is to "demonstrate the desired functionality" of verifying calibration, linear operating range, and reportable range for TDM methods, similar to the predicate device. This functionality is demonstrated through testing on commonly used automated TDM systems and other analytical methods.

• Carbamazepine by fluorescence polarization immunoassay: Demonstrated a "significant miscalibration believed to be real." This implies the verifiers successfully identified a miscalibration, fulfilling their intended purpose of verifying.
• GED reagents for acetaminophen: Gave results that "might indicate incompatibility" or a miscalibration. However, a level-correlated, proportional colorimetric response was observed, suggesting the verifiers were providing expected responses within the method's context.
• EMIT reagents for ethosuximide: Reacted with an interferent in the AC/AD base matrix, leading to the conclusion that "this product is not useful with the EMIT ethosuximide reagents." This identifies a specific limitation where the verifiers do not perform as intended, which is also a valuable outcome of a verification study. |
  | Verify Linear Operating Range | Demonstrated for most methods tested: Similar to calibration, the verifiers were used to assess linearity. The text states: "Most methods tested demonstrated the desired functionality of the product," which encompasses verifying the linear operating range. For the methods where issues were noted (Carbamazepine, Acetaminophen GED, Ethosuximide EMIT), the verifiers either indicated a problem with linearity/calibration or a specific incompatibility, thereby fulfilling their role in assessing the linear operating range and reportable range, even if the result was a limitation. |
  | Verify Reportable Range | Demonstrated for most methods tested: Similar to calibration and linearity, the verifiers' ability to assess the reportable range of TDM methods was implied as part of the "desired functionality" demonstrated across the tested systems. |
  | Substantial Equivalence to Predicate Device | Conclusion: "Based upon the purpose of the device, the descriptions and labeling of the predicate device, and upon the safety and efficacy using multiple instruments and methods, and stability data generated for the AC/AD Linearity Verifiers, the product is substantially equivalent to the predicate device." |

2. Sample Size for the Test Set and Data Provenance

• Sample Size for Test Set: The document does not specify a numerical "sample size" in terms of how many individual tests or replicates were performed for each analyte on each system. It mentions that the verifiers contain "five levels" and were tested on "three commonly used automated therapeutic drug monitoring systems," "two colorimetric methods," and "HPLC."
• Data Provenance: The document does not explicitly state the country of origin. Given the submission to the FDA in the US, it is highly likely that the testing was conducted in the US. The data appears to be retrospective in the sense that the studies were performed to validate the product before market submission, rather than a prospective trial of a new clinical diagnostic method.

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

This type of device (linearity verifier for analytical instruments) does not typically involve human experts establishing ground truth in the way a diagnostic imaging study would. The "ground truth" for the linearity verifiers is established through their intrinsic formulation (gravimetrically and traceable calibration) and their expected behavior when analyzed on instrument systems. The "experts" in this context would be the analytical chemists or laboratorians who designed the product and interpreted the results of the performance testing on the various instrument platforms. The document does not specify the number or qualifications of these individuals, but their expertise is implied by the technical nature of the submission.

4. Adjudication Method for the Test Set

Not applicable. As described above, the "ground truth" is analytical/technical, not based on expert adjudication of clinical cases.

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

Not applicable. This device is an in vitro diagnostic reagent (linearity verifier), not a diagnostic algorithm or imaging device requiring a MRMC study. Its function is to assess instrument performance, not to aid human readers in interpreting clinical cases.

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

This concept is not directly applicable. The "device" itself is a set of calibrators (reagents). It interacts with instruments to produce results. The "performance" is how reliably these calibrators allow the instrument and method to demonstrate proper calibration, linearity, and reportable range without human intervention in the result generation, although human interpretation of these instrument results is required. The testing described focuses on this standalone performance of the verifiers across different instrument platforms.

7. Type of Ground Truth Used

The ground truth used for the AC/AD Linearity Verifiers is based on:

• Intrinsic formulation: Gravimetric and traceable calibration of the analytes within the verifiers. This means the true concentration of each analyte at each level is known by design.
• Expected analytical response: The verifiers are designed to produce a linear and proportional response when tested on properly calibrated and functioning TDM methods and instruments. Deviations from this expected response (e.g., miscalibration, non-linearity, interference) reveal issues with the method/instrument, which is the intended purpose of the verifiers.

8. Sample Size for the Training Set

Not applicable. This device is a linearity verifier, not an algorithm that requires a "training set" in the machine learning sense. The concentrations within the verifiers are pre-determined by design and chemical formulation.

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

Not applicable, as there is no "training set" for this type of device. The "ground truth" (i.e., the exact concentration of each analyte at each level within the verifier vials) is established through precise manufacturing processes, including gravimetric measurements and traceability to reference standards.

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