(11 days)
The Pan Probe Biotech LiveSure™ Barbiturates Screen Test Card and Test Strip devices are rapid in vitro diagnostic (IVD) qualitative lateral flow immuno-chromatographic competitive urinary assays for the detection of Barbiturates (e.g., Amobarbital, Butalbital, Pentobarbital, Secobarbital, Phenobarbital, Phenobarbital, etc.), analogs and metabolites (collectively termed: BAR) in human urine at the NIDA (National Institute on Drug Abuse) modified (Substance Abuse and Mental Health Services Administration) cut-off level of 300 ng BAR/M. The cut-off for both LiveSure™ Test Card and Test Strip device methods has been set at 300 ng BAR drug/ml based upon calibration using Secobarbital as a prototype Barbiturate/BAR drug, and ng BRK drugmit bagod upen vith a GCMS method for the quantitation of all the Secobarbital standard and urine test solutions. These IVD Tests are intended for visual, qualitative screening, for professional use only, and are not intended for quantitative results, nor for over the counter sales. Pan Probe Biotech LiveSure™ BAR Screen Tests for BAR provide only preliminary analytical data. A more specific quantitative alternative method must be used in order to obtain a confirmed analytical result. Both NIDA and SAMHSA have established gas chromatography/mass spectrometry (GC/MS) as a preferred confirmatory method. Clinical considerations and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.
The Pan Probe Biotech LiveSure™ Barbiturates Screen Test Card and Test Strips (i.e., LiveSure™ Barbiturates) devices are rapid qualitative competitive chromatographic IVD immunoassays, in which chemically labeled drug conjugate competes with any Barbiturate (BAR) drugs, analogs or metabolites that may be present in test urinary samples for limited specific antibody binding sites. LiveSure™ Barbiturates devices have a unique membrane pre-coated with a gold conjugate immunoassay indicator that is used is pre-labeled with specific monoclonal antibody from mouse directed against BAR. Each Test Strip and Test Card consists of a membrane absorbent pad having a gold-probe-conjugate pre-labeled with specific monoclonal antibody from mouse that is directed against BAR, and a chromatographic membrane precoated with a chemically modified Barbiturate [Secobarbital] drug-conjugate as a capture reagent. The Test region of each device has been layered with a Barbiturate [Secobarbital] drug-conjugate as a 1" capture region of dail the Process Control region has been pre-coated with a 200 anti-mouse antibody reagent derived from goat. A pink colored antibody-colloidal gold conjugate pad is placed to the right of a test strip. In the absence of BAR drugs, analogs or metabolites in urine, pink colored antibodycolloidal gold conjugates move chromatographically along with a urinary sample on the membrane by capillary action. Antibody-colloidal gold conjugate binds to BAR-drug conjugate, forming an antibodyantigen complex. This antibody-BAR-drug conjugate appears as a second visible pink colored band and as a captured reagent at the test region. Any BAR drugs, analogs or metabolites that are present in a sample urine act as antigens, competing with BAR-drug conjugate at the test band region for limited BAR-antibody binding sites on antibody-colloidal gold conjugate. When a sufficient concentration of urinary BAR drugs, analogs or metabolites are present, these analytes block the limited antibody binding sites. This blockagebinding prevents attachment of pink colored antibody-colloidal gold conjugate at the BAR-drug conjugate zone located at the test band region. To serve as a procedural control, a pink colored band in a control region will always appear, regardless of presence of BAR in urine samples. Thus, negative urine samples produces two pink colored bands, while positive urine samples only one pink colored band.
Here's a breakdown of the acceptance criteria and study details for the LiveSure™ BARBITURATES SCREEN TESTS, based on the provided 510(k) submission:
Acceptance Criteria and Device Performance Study
The primary study performed was a clinical evaluation comparing the LiveSure™ Barbiturates Screen Test Card and Test Strip devices against a predicate device (EMIT® II Assay) and a confirmatory method (GC/MS).
1. Table of Acceptance Criteria and Reported Device Performance
The submission doesn't explicitly define "acceptance criteria" as a separate, pre-specified table with target values. Instead, the study results are presented as evidence of equivalency and accuracy. Based on the "Summary Statement of Safety and Effectiveness," the implied acceptance criteria are high agreement percentages with GC/MS for both positive and negative results, and equivalency to the predicate EMIT® II Assay.
| Performance Metric | Implied Acceptance Criteria (Goal) | LiveSure™ Test Card Performance | LiveSure™ Test Strip Performance | Predicate (EMIT® II) Performance against GC/MS |
|---|---|---|---|---|
| Agreement with GC/MS (Positive) | High agreement (e.g., >95-100%) | 100% | 100% | 100% |
| Agreement with GC/MS (Negative) | High agreement (e.g., >95-100%) | 100% | 99.6% | 99.7% |
| Agreement with EMIT® II (Positive) | 100% | 100% | 100% | N/A (predicate) |
| Specificity vs EMIT® II (Negative) | High specificity (e.g., >95-100%) | 100% | 99.6% | N/A (predicate) |
| Overall Accuracy vs GC/MS | High accuracy (e.g., >95-100%) | 335/335 (100%) | 334/335 (99.7%) | 334/335 (99.7%) |
| False Positives (at ±25% of NIDA/SAMHSA cut-off) | 0 false positives | 0 | 0 | N/A (not reported for predicate) |
Note: The phrasing "essentially showing equivalency" and the high agreement percentages suggest an implicit acceptance of very strong correlation and accuracy compared to the gold standard and predicate.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 335 urine samples.
- Data Provenance: The submission does not explicitly state the country of origin. It indicates "independent clinical testing...at an external reference laboratory." It is a prospective study as it involves collecting and testing samples for comparison.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- The study used GC/MS (Gas Chromatography/Mass Spectrometry) as the confirmatory method for establishing the ground truth for barbiturates presence and concentration. GC/MS is an analytical chemistry technique, not a human expert. Therefore, the concept of "experts establishing ground truth" in the traditional sense (e.g., radiologists interpreting images) does not directly apply here. Instead, it relies on the established accuracy and reliability of the GC/MS method.
- The qualifications of the personnel operating the GC/MS are not specified, but it would typically be conducted by trained laboratory technicians or chemists in a certified laboratory setting.
4. Adjudication Method for the Test Set
- Adjudication, as in multiple human readers resolving discrepancies, is not applicable in this context. The LiveSure™ devices provide a visual qualitative result (presence or absence of a band), and the GC/MS provides a quantitative, definitive result. Discrepancies would be resolved by the GC/MS result being the higher standard.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
- No, an MRMC comparative effectiveness study was not done. This type of study typically applies to imaging diagnostics where multiple human readers interpret results, and the AI's impact on their performance is measured.
- This submission describes a standalone performance study of an in-vitro diagnostic (IVD) device, compared to a predicate and a gold standard.
6. If a Standalone Performance Study was done
- Yes, a standalone performance study was done. The results reported (e.g., "LiveSure™ Barbiturates Test Card and Test Strip gave overall accuracy results of 335/335 (100%) and 334/335 (99.7%), respectively, versus GC/MS quantitative BAR data") directly reflect the algorithm's (or device's) own performance in identifying barbiturates in urine samples without human interpretation of the device's output. The device itself produces a visual result which is then read.
7. The Type of Ground Truth Used
- The primary ground truth used was GC/MS quantitative data. This is considered a highly reliable and definitive analytical method for drug identification and quantification in toxicology. The submission explicitly states, "Both NIDA and SAMHSA have established gas chromatography/mass spectrometry (GC/MS) as a preferred confirmatory method."
8. The Sample Size for the Training Set
- The submission does not explicitly state a separate training set sample size. This is common for this type of IVD device where the "training" primarily involves internal development and optimization of the immunoassay components (antibodies, conjugates, cut-off levels) to achieve desired sensitivity and specificity.
- The "in-house testing of LiveSure™ Barbiturates Screen Test Strip devices against EMIT® II Assay" mentioned could be interpreted as part of the development/internal validation process that predates the formal clinical study, but it's not delineated as a distinct "training set" in the context of machine learning.
9. How the Ground Truth for the Training Set Was Established
- Since a distinct "training set" is not detailed, the method for establishing its ground truth is also not explicitly described. However, given the context, any internal development or optimization (analogous to 'training') would likely have used:
- Known spiked samples: Urine samples with precisely known concentrations of barbiturates (e.g., using Secobarbital as a prototype, as mentioned for calibration).
- Reference methods: Comparison against established laboratory methods, potentially including early GC/MS analyses or other validated techniques, to ensure the device's performance aligned with expected results during development. The mention of using "Secobarbital as a prototype Barbiturate/BAR drug, and with a GCMS method for the quantitation of all the Secobarbital standard and urine test solutions" points to how the calibration and development (training) would have leveraged GC/MS for accuracy.
§ 862.3150 Barbiturate test system.
(a)
Identification. A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.(b)
Classification. Class II (special controls). A barbiturate test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. 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, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).