(111 days)
evidence® Benzodiazepine Assay: The evidence® Benzodiazepine test has been designed for use on the evidence@analyser for qualitative detection of benzodiazepine compounds. drugs with sedative and hypnotic effects, in urine using a cut-off concentration of 200ng/ml. Qualitative results obtained can be utilized in the diagnosis and treatment of benzodiazepine use or overdose. evidence® performs two Benzodiazeoine based on - oxazepam (Benzodazepine Assay 1) and lorazepam assavs (Benzodiazepine Assay 2). This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography / mass spectrometry (GC/MS) is the preferred method. Clinical consideration and professional judgement should be applied to any drug of abuse test result, particularly when preliminary positive results are used. The evidence® benzodiazenine class assay must only be used by suitably qualified laboratory personnel under appropriate laboratory conditions.
The evidence® Drugs of Abuse Calibrators: The evidence®Drugs of Abuse Calibrators are liquid Calibrators containing benzoylecgonine, amphetamine, methamphetamine, methadone, morphine sulphate pentahydrate, Phenobarbital, 11-nor-D9-THC-9 carboxylic acid, oxazepam and lorazepam. There are 9 levels of calibrator. They have been developed for use in calibration of the evidence® system. The evidence® Drugs of Abuse Calibrators must only be used by suitably qualified laboratory personnel under appropriate laboratory conditions.
evidence® Benzodiazepine Assay: Qualitative detection of benzodiazepine compounds in urine using a cut-off concentration of 200ng/ml. Performs two assays based on oxazepam and lorazepam.
The evidence® Drugs of Abuse Calibrators: Liquid Calibrators containing benzoylecgonine, amphetamine, methamphetamine, methadone, morphine sulphate pentahydrate, Phenobarbital, 11-nor-D9-THC-9 carboxylic acid, oxazepam and lorazepam. 9 levels of calibrator for use in calibration of the evidence® system.
1. Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (from the predicate device) | Reported Device Performance (BENZODIAZEPINE CLASS ASSAY) |
|---|---|---|
| Accuracy against GC/MS | Not explicitly stated in the provided text, but implied as the preferred confirmation method. | 100% agreement with GC/MS for positive and negative samples at the 200 ng/ml cutoff. |
| Cross-reactivity | Not explicitly stated in the provided text, but implied by the need for specificity. | Various benzodiazepine compounds showed reactivity (ranging from 100% to <0.01%) at different concentrations. Other drugs and compounds showed no or minimal cross-reactivity. |
| Precision (Within-run) | Not explicitly stated in the provided text, but implied by standard laboratory practice. | For Benzodiazepine 1: %CV ranged from 0.0% to 1.1% for positive samples and 1.9% to 2.8% for negative samples. For Benzodiazepine 2: %CV ranged from 0.0% to 0.5% for positive samples and 1.6% to 2.0% for negative samples. |
| Precision (Between-run) | Not explicitly stated in the provided text, but implied by standard laboratory practice. | For Benzodiazepine 1: %CV ranged from 0.0% to 1.7% for positive samples and 2.1% to 2.7% for negative samples. For Benzodiazepine 2: %CV ranged from 0.0% to 1.2% for positive samples and 1.8% to 2.5% for negative samples. |
2. Sample Size and Data Provenance
- Test Set Sample Size:
- GC/MS Comparison: 288 samples (144 negative, 144 positive) were tested for each assay.
- Cross-reactivity: Varies depending on the compound tested, but numerous compounds were evaluated at different concentrations.
- Precision:
- Within-run: 20 replicates of each sample were tested.
- Between-run: 20 replicates of each sample were tested over 5 days.
- Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective for the clinical samples. The study appears to be an analytical validation conducted internally by Randox Laboratories.
3. Number of Experts and Qualifications for Ground Truth Establishment (Test Set)
- Number of Experts: Not applicable in the context of this device being a chemical assay.
- Qualifications of Experts: Not applicable. The ground truth for the clinical sample comparison was established by Gas Chromatography/Mass Spectrometry (GC/MS), which is an objective chemical method.
4. Adjudication Method for the Test Set
- Not applicable for a chemical assay. The comparison was made against GC/MS as the gold standard, not expert consensus.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done. This is a standalone chemical assay, not an imaging device or a diagnostic tool that relies on human interpretation.
6. Standalone Performance Study
- Yes, a standalone study was performed. The described performance data (accuracy against GC/MS, cross-reactivity, and precision) are all measures of the algorithm's (the assay's) performance without human-in-the-loop assistance for interpretation. The assay provides a qualitative result (positive/negative) automatically based on a predefined cutoff.
7. Type of Ground Truth Used
- The primary ground truth used for establishing the accuracy of the BENZODIAZEPINE CLASS ASSAY was Gas Chromatography/Mass Spectrometry (GC/MS). For the precision and cross-reactivity studies, known concentrations of various substances were used.
8. Sample Size for the Training Set
- The document does not explicitly mention a "training set" in the context of machine learning, as this is a chemical assay with established analytical principles, not an AI/ML algorithm. The development of such an assay involves extensive laboratory work to optimize reagents and reaction conditions, which could be considered an analogous "training" phase to achieve desired sensitivity and specificity. However, specific sample sizes for this development are not provided.
9. How the Ground Truth for the Training Set Was Established
- Not applicable as this is not an AI/ML algorithm with a distinct training set. The "ground truth" during the development of the assay would have been established through a combination of:
- Known concentrations of benzodiazepine compounds and their metabolites.
- Known concentrations of potential cross-reactants.
- Reference analytical methods (like GC/MS) used during the assay's development to ensure its chemical specificity and sensitivity.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes representing the department's mission. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the eagle.
Public Health Service
MAY 1 7 2005
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Dr. Pauline Armstrong Regulatory Affairs Randox Laboratories, Ltd. 55 Diamond Road Crumlin, Co.Antrim United Kingdom, BT29 4QY
K050179 Re:
K050179
Trade/Device Name: BENZODIAZEPINE CLASS ASSAY AND evidence® DRUGS OF ABUSE CALIBRATORS Regulation Number: 21 CFR 862.3170 Regulation Name: Benzodiazepine test system Regulatory Class: Class II Product Code: JXM, DKB Dated: May 10, 2005 Received: May 12, 2005
Dear Dr. Armstrong:
We have reviewed your Section 510(k) premarket notification of intent to market the device wt nave reviewed your becarely be device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for ass stated in the encreations of the enactment date of the Medical Device Amendments, or to conninered pror co ria) 2005 reclance with the provisions of the Federal Food, Drug, de nocs that have act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The r ou may, there recovisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device It inay be subject to suen dadnetial come of CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean I Teast be advised that I Dri bisean.co to your device complies with other requirements of the Act that I Dri has made a actor regulations administered by other Federal agencies. You must or any I cactar suttates and regaranents, including, but not limited to: registration and listing (21 comply with an the Prec (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) This letter whitanow you to oegin maneting your maneting your device of your device to a legally premarket notification: "The PDF in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, If you destic specific information as varies in the promotive, please contact the Office of In of questions on the prometicalization and Safety at (240) 276-0484. Also, please note the Viro Diagnostic Dorec Drailance by reference to premarket notification" (21 CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Tou may other of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Carol C. Benem
Carol C. Benson, M.A. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
NOT KNOWN 510(k) Number (if known):
Device Name: BENZODIAZEPINE CLASS ASSAY ANDevidence® DRUGS OF ABUSE CALIBRATORS
Indications For Use:
evidence® Benzodiazepine Assay
The evidence® Benzodiazepine test has been designed for use on the evidence@analyser for qualitative detection of benzodiazepine compounds. drugs with sedative and hypnotic effects, in urine using a cut-off concentration of 200ng/ml. Qualitative results obtained can be utilized in the diagnosis and treatment of benzodiazepine use or overdose. evidence® performs two Benzodiazeoine based on - oxazepam (Benzodazepine Assay 1) and lorazepam assavs (Benzodiazepine Assay 2).
This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography / mass spectrometry (GC/MS) is the preferred method. Clinical consideration and professional judgement should be applied to any drug of abuse test result, particularly when preliminary positive results are used.
The evidence® benzodiazenine class assay must only be used by suitably qualified laboratory personnel under appropriate laboratory conditions.
The evidence® Drugs of Abuse Calibrators.
The evidence®Drugs of Abuse Calibrators are liquid Calibrators containing benzoylecgonine, amphetamine, methamphetamine, methadone, morphine sulphate pentahydrate, Phenobarbital, 11-nor-D9-THC-9 carboxylic acid, oxazepam and lorazepam.
There are 9 levels of calibrator. They have been developed for use in calibration of the evidence® system.
The evidence® Drugs of Abuse Calibrators must only be used by suitably qualified laboratory personnel under appropriate laboratory conditions
Prescription Use (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
1
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Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K050179
§ 862.3170 Benzodiazepine test system.
(a)
Identification. A benzodiazepine test system is a device intended to measure any of the benzodiazepine compounds, sedative and hypnotic drugs, in blood, plasma, and urine. The benzodiazepine compounds include chlordiazepoxide, diazepam, oxazepam, chlorzepate, flurazepam, and nitrazepam. Measurements obtained by this device are used in the diagnosis and treatment of benzodiazepine use or overdose and in monitoring levels of benzodiazepines to ensure appropriate therapy.(b)
Classification. Class II (special controls). A benzodiazepine 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).