(79 days)
The Lin-Zhi Multiple Analyte Set A, B, and C Urine Drugs of Abuse Calibrators are intended for in vitro diagnostic use for the calibration of assays for the analytes currently listed in the package insert: Benzoylecgonine, Methamphelamine, Methadone, 6-acetylmorphine, MDMA, Morphine, Oxazepan, and Secobarbital. The calibrators are designed for prescription use with homogeneous enzyme immunoassays on automated clinical chemistry analyzers.
The Lin-Zhi Multiple Analyte Set A, B, and C Urine Drugs of Abuse Controls are intended for in vitro diagnostic use to monitor the performance of assays for the analytes currently listed in the package insert: Benzoylecgonine, Methamphelamine, Methadone, 6-acetylmorphine, Oxazepan, and Secobarbital. The controls are designed for prescription use with homogeneous enzyme immunoassays on automated clinical chemistry analyzers.
All of the LZI Multiple Analyte Set A, B, and C Drugs of Abuse 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 DAU Calibrator is a processed, drug-free human urine matrix in human urine with sodium azide (0.09%) as preservative. The Low. Cutoff. Intermediate, and High Calibrators, as well as the 2 levels of Controls are prepared by spiking known concentrations of drug analyte into the Negative DAU Calibrator matrix. These five calibrators and two controls are sold as individual bottles.
Acceptance Criteria and Device Performance Study
This document describes the acceptance criteria and study proving the performance of the LZI Multiple Analyte Set A, B, and C Drugs of Abuse Calibrators and Controls. These devices are intended for in vitro diagnostic use for the calibration and monitoring of homogeneous enzyme immunoassays for drugs of abuse in human urine.
1. Table of Acceptance Criteria and Reported Device Performance
The device performance was evaluated based on stability, traceability, and value assignment, with the primary acceptance criteria being that the calibrators and controls should not vary by more than ±10% in stability studies and that assigned values are within ±10% of target concentrations.
| Acceptance Criterion | Reported Device Performance |
|---|---|
| Stability | Not vary greater than ±10% in individual concentration or total separation for Cold (2-8 ℃), Room Temperature, and Accelerated (30 ℃) Temperature studies. |
Exceptions:
- Set A: 6-acetylmorphine (6AM) Calibrator and Control slightly differed.
- Set B and C: Benzodiazepine (Oxazepam) Calibrator and Control slightly differed.
All calibrators and controls held steady when stored at 2 ℃ to 8 ℃ (refrigerated) up to Day 366 real time. A shelf-life of at least 12 months at 2-8 °C is supported. |
| Traceability and Value Assignment | Verified by GC/MS to be within ± 10% of the target concentration. | The standard solution (starting material) was found to be 99% purity by GC/MS. Secondary stock solutions' concentrations were verified gravimetrically using NIST traceable weights. The final spiked calibrator and control concentrations were verified by GC/MS to be within ± 10% of the target concentration. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state a specific "sample size" for a test set in the traditional sense of patient samples. Instead, the testing involved:
- Stability Studies: Measurements were taken on various calibrator and control sets at multiple temperatures (Cold: 2-8 ℃, Room Temperature, Accelerated: 30 ℃) over a period up to Day 366. The number of individual vials or replicates per concentration for these studies is not specified, but it covered all analytes across Sets A, B, and C.
- Traceability and Value Assignment: This involved
- One commercial standard stock solution per analyte (purity 99%, verified by GC/MS).
- Secondary stock solutions (concentration verified gravimetrically).
- Final calibrator and control products (prepared by spiking into negative urine matrix and verified by GC/MS). The exact number of individual samples for the GC/MS verification is not detailed.
Data Provenance: The study appears to be an internal laboratory study conducted by Lin-Zhi International, Inc. given the context of a 510(k) submission. The data is prospective, generated specifically for this submission to demonstrate substantial equivalence. The country of origin of the data is implicitly the USA, where the company is located.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of device (calibrators and controls for in vitro diagnostics) does not rely on human expert interpretation or ground truth in the way medical imaging or clinical diagnostic devices would. Instead:
- Ground Truth (Reference Values): The "ground truth" for the calibrators and controls is established by the precisely known concentrations of drug analytes spiked into the negative urine matrix. These concentrations are analytically verified.
- Verification Method: Gas Chromatography/Mass Spectrometry (GC/MS) is cited as the method for verifying the purity of starting materials and the final concentrations in the calibrators/controls. GC/MS is a highly accurate and widely accepted analytical technique for confirming the presence and concentration of substances.
Therefore, no clinical experts (e.g., radiologists) were used. The "experts" in this context would be analytical chemists or lab personnel skilled in performing and interpreting GC/MS results and gravimetric measurements. Their specific qualifications are not detailed, but their work is grounded in established analytical chemistry principles.
4. Adjudication Method for the Test Set
Not applicable. As described above, the ground truth is analytically determined by precise spiking and confirmed by GC/MS, not by human interpretation requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. An MRMC comparative effectiveness study is not applicable to this device. This device is a set of calibrators and controls used to standardize and monitor automated laboratory assays, not an AI or diagnostic tool that involves human interpretation of cases.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, in a sense. The "performance" being evaluated is the chemical and physical characteristics of the calibrators and controls themselves (stability, accurate concentration). This evaluation is inherently "standalone" in that it assesses the product's intrinsic properties through analytical methods (spectrometry, gravimetry) without human intervention in the result generation or interpretation of a diagnostic outcome. The calibrators/controls are not an "algorithm," but their performance is objectively measured.
7. The Type of Ground Truth Used
The ground truth used is based on analytical confirmation of spiked concentrations using:
- Gravimetrically prepared concentrations: The known amounts of drug analyte spiked into the urine matrix.
- Mass Spectrometry (GC/MS): An independent analytical method used to verify the purity of starting materials and the final concentrations in the calibrators and controls to ensure they are within ±10% of the target concentration.
This is a form of highly precise reference standard or chemical assay ground truth.
8. The Sample Size for the Training Set
Not applicable. This device is a set of calibrators and controls, not an AI/machine learning algorithm that requires a "training set." Its performance is based on its chemical manufacturing and analytical verification, not on learning from data.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As explained in point 8, there is no training set for this type of device.
§ 862.3200 Clinical toxicology calibrator.
(a)
Identification. A clinical toxicology calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. A clinical toxicology calibrator can be a mixture of drugs or a specific material for a particular drug (e.g., ethanol, lidocaine, etc.). (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.