(83 days)
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.
§ 862.3280 Clinical toxicology control material.
(a)
Identification. A clinical toxicology control material is a device intended 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. This generic type of device includes various single, and multi-analyte control materials.(b)
Classification. Class I (general 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.