(29 days)
Not Found
No
The device description and performance studies focus on a homogeneous enzyme immunoassay and spectrophotometric measurement, with no mention of AI or ML techniques.
No.
This device is an in vitro diagnostic (IVD) assay designed to detect cocaine metabolites in human urine. It is used for analytical testing and does not directly provide therapy or treatment to a patient.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the device is "intended for the qualitative and/or semi-quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine," which is a diagnostic purpose. Furthermore, it mentions "For In Vitro Diagnostic Use Only," confirming its diagnostic nature.
No
The device description clearly outlines the use of liquid reagents and a homogeneous enzyme immunoassay, which are physical components, not software. The performance studies also focus on the analytical performance of these reagents.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is "intended for the qualitative and/or semi- quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine". This indicates that the device is used to test a sample taken from the human body (urine) in vitro (outside the body) to provide diagnostic information (presence and/or amount of cocaine metabolite).
- "For In Vitro Diagnostic Use Only": The final sentence of the "Intended Use / Indications for Use" section clearly states "For In Vitro Diagnostic Use Only." This is a standard labeling requirement for IVD devices.
- Device Description: The description details a laboratory-based assay using reagents to analyze a biological sample (urine). This is characteristic of an IVD.
- Performance Studies: The description of performance studies, including method comparison with LC-MS/MS and evaluation of analytical performance metrics, are typical for the validation of an IVD device.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K960187) indicates that this device is being compared to a previously cleared IVD device, which is a common regulatory pathway for IVDs.
N/A
# Intended Use / Indications for Use
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi- quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL.
The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC- MS/MS) or permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/ tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications.
Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.
# Product codes (comma separated list FDA assigned to the subject device)
DIO
# Device Description
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-to-use liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 mm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
The assay consists of reagents (A and E).
Reagent A: Contains mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as preservative.
Reagent E: Contains benzoylecgonine analog labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with sodium azide as preservative.
# Mentions image processing
Not Found
# Mentions AI, DNN, or ML
Not Found
# Input Imaging Modality
Not Found
# Anatomical Site
human urine
# Indicated Patient Age Range
Not Found
# Intended User / Care Setting
Trained professionals
# Description of the training set, sample size, data source, and annotation protocol
Not Found
# Description of the test set, sample size, data source, and annotation protocol
Not Found
# Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
1. **Analytical Performance:**
* **Precision:** Studies performed in accordance with CLSI Guideline EP05-A3. Samples prepared by spiking Benzoylecgonine (Cocaine Metabolite) into drug-free urine at cutoff, 25%, 50%, 75%, and 100% above and below the cutoff. Tested in both qualitative and semi-quantitative modes. Results generated by testing all samples in replicates of 2, twice per day for 20 days, total n=80.
* Qualitative Study Analysis for 150 ng/mL cutoff: At 150 ng/mL, 22/58 positive/negative results. At 187.5 ng/mL and above, 0/80 negative/positive results.
* Qualitative Study Analysis for 300 ng/mL cutoff: At 300 ng/mL, 31/49 positive/negative results. At 375 ng/mL and above, 0/80 negative/positive results.
* Semi-Quantitative Study Analysis for 150 ng/mL cutoff: At 150 ng/mL, 19/61 positive/negative results. At 187.5 ng/mL and above, 0/80 negative/positive results.
* Semi-Quantitative Study Analysis for 300 ng/mL cutoff: At 300 ng/mL, 22/58 positive/negative results. At 375 ng/mL and above, 0/80 negative/positive results.
* **Spike Recovery:** Study performed with 21 replicates. Samples spiked with Benzoylecgonine (Cocaine Metabolite) at cutoff calibrator and control levels into drug-free urine. Tested in both qualitative and semi-quantitative mode.
* Qualitative Data for 150 ng/mL cutoff: 21 replicates at 112.5 ng/mL (All Negative), 21 replicates at 187.5 ng/mL (All Positive). No overlap.
* Qualitative Data for 300 ng/mL cutoff: 21 replicates at 225 ng/mL (All Negative), 21 replicates at 375 ng/mL (All Positive). No overlap.
* **Analytical Recovery and Linearity:** Linearity studies performed in accordance with CLSI Guideline EP06-A. Drug-free urine spiked to 1000 ng/mL Benzoylecgonine and diluted to generate 9 intermediate levels. Each sample run in replicates of five in semi-quantitative mode. Percent recovery compared to expected target value. Recovery ranged from 95.9% to 108.9% for spiked samples.
* **Method Comparison and Accuracy:** Method comparison study performed in accordance with CLSI Guideline EP09-A3. One hundred patient samples analyzed by DRI Cocaine Metabolite Assay in qualitative and semi-quantitative modes and compared to LC-MS/MS. Overall concordance is 100%.
* Semi-Quantitative Mode Accuracy for 150 ng/mL cutoff: Agreement among Positives: 50/50 = 100%. Agreement among Negative: 50/50 = 100%.
* Semi-Quantitative Mode Accuracy for 300 ng/mL cutoff: Agreement among Positives: 50/50 = 100%. Agreement among Negative: 50/50 = 100%.
* Qualitative Accuracy for 150 ng/mL cutoff: Agreement among Positives: 50/50 = 100%. Agreement among Negative: 50/50 = 100%.
* Qualitative Accuracy for 300 ng/mL cutoff: Agreement among Positives: 50/50 = 100%. Agreement among Negative: 50/50 = 100%.
* **Specificity (Cross-reactivity):** Cross-reactivity of Cocaine and its metabolites evaluated. Structurally unrelated compounds evaluated by adding them to Benzoylecgonine spiked urine at various concentrations. Tested low and high controls detected accurately, indicating no significant cross-reactivity.
* **Interference:** Interference studies performed in accordance with CLSI Guideline EP07-A2, using both qualitative and semi-quantitative modes. Potential interference of pH, endogenous and exogenous physiologic substances assessed. Controls detected accurately, indicating no interference.
* **Specific Gravity:** Drug-free urine samples with specific gravity from 1.000 to 1.030 spiked with Benzoylecgonine. Evaluated in qualitative and semi-quantitative modes. Controls detected accurately, no interference observed.
# Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
* Overall concordance between LC-MS/MS and DRI Cocaine Metabolite Assay is 100%.
* Semi-Quantitative Mode Accuracy for 150 ng/mL cutoff: Agreement among Positives: 100%. Agreement among Negative: 100%.
* Semi-Quantitative Mode Accuracy for 300 ng/mL cutoff: Agreement among Positives: 100%. Agreement among Negative: 100%.
* Qualitative Accuracy for 150 ng/mL cutoff: Agreement among Positives: 100%. Agreement among Negative: 100%.
* Qualitative Accuracy for 300 ng/mL cutoff: Agreement among Positives: 100%. Agreement among Negative: 100%.
# Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
[K960187](https://510k.innolitics.com/search/K960187)
# Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
# Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.3250 Cocaine and cocaine metabolite test system.
(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite 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).
0
Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. Food & Drug Administration" in blue.
July 6, 2018
Microgenics Corporation Emily Chien Regulatory Affairs Specialist II 46500 Kato Road Fremont, California 94538
Re: K181499
Trade/Device Name: DRI Cocaine Metabolite Assay Regulation Number: 21 CFR 862.3250 Regulation Name: Cocaine and cocaine metabolite test system Regulatory Class: Class II Product Code: DIO Dated: June 5. 2018 Received: June 7, 2018
Dear Emily Chien:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic 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 general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Paula Caposino -S
for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
| DEPARTMENT OF HEALTH AND HUMAN SERVICES | |
|---|---|
| Food and Drug Administration | |
| Indications for Use | |
| Form Approved: OMB No. 0910-0120 | |
| Expiration Date: 06/30/2020 | |
| See PRA Statement below. | |
| 510(k) Number ( if known ) | K181499 |
| Device Name | DRI Cocaine Metabolite Assay |
| Indications for Use (Describe) | The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi- quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL. |
| The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC- MS/MS) or permitting laboratories to establish quality control procedures. | |
| The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/ tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications. | |
| Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only. | |
| Type of Use (Select one or both, as applicable) | |
| Prescription Use (Part 21 CFR 801 Subpart D) | |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the
time to review instructions, search existing data sources, gather and maintain the data needed and complete
and review the collection of information. Send comments regarding this burden estimate or any other aspect
of this information collection, including suggestions for reducing this burden, to:
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Office of Chief Information Officer
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"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of
information unless it displays a currently valid OMB number."
FORM FDA 3881 (7/17)
.
3
5. 510(k) Summary
This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of Safe Medical Device Act of 1990 and 21 CFR 807.92.
A. Device Information
| Category | Comments |
|---|---|
| Sponsor: | Microgenics Corporation |
| Thermo Fisher Scientific | |
| 46500 Kato Road | |
| Fremont, CA 94538 | |
| Phone: 510-979-5000 | |
| FAX: 510-979-5002 | |
| Correspondent Contact | |
| Information: | Emily Chien |
| Regulatory Affairs Specialist II | |
| Email: Emily.Chien@thermofisher.com | |
| Phone: 510-979-5000 | |
| FAX: 510-979-5002 | |
| Device Common Name: | Cocaine Metabolite Enzyme Immunoassay |
| Trade or Proprietary Name | DRI Cocaine Metabolite Assay |
| Candidate Device Product | |
| Code, Classification, | |
| Classification Name & | |
| Panel | DIO, Class II, 21 CFR 862. 3250 - Cocaine Metabolite |
| Test System, 91 - Toxicology |
Predicate Device Information:
| Predicate Device: | Cocaine Metabolite Enzyme Immunoassay |
|---|---|
| Predicate Device | |
| Manufacturer: | Diagnostic Reagents, Inc. |
| Predicate Device Premarket | |
| Notification #: | K960187 |
B. Date Summary Prepared July 06, 2018
July 06, 2018
C. Description of Device
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-touse liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody
4
binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 mm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
The assay consists of reagents (A and E).
Reagent A: Contains mouse monoclonal anti-benzoylecgonine antibody, glucose-6-phosphate (G6P), and nicotinamide adenine dinucleotide (NAD) in Tris buffer with sodium azide as preservative.
Reagent E: Contains benzoylecgonine analog labeled with glucose-6-phosphate dehydrogenase (G6PDH) in HEPES buffer with sodium azide as preservative.
D. Intended Use
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay intended for the qualitative and/or semi-quantitative determination of benzoylecgonine (Cocaine Metabolite) in human urine at a cutoff concentration of either 150 ng/mL or 300 ng/mL.
The semi-quantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.
The assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography / Mass spectrometry (GC/MS) or Liquid chromatography/tandem mass spectrometry (LC-MS/MS) is the preferred confirmatory method. Tests for cocaine metabolite cannot distinguish between abused drugs and certain prescribed medications.
Clinical and professional judgment should be applied to any drug of abuse test result, particularly when preliminary results are used. For In Vitro Diagnostic Use Only.
5
E. Comparison to Predicate Device
| Characteristics | Candidate Device:
DRI Cocaine
Metabolite Assay | Predicate Device:
Cocaine Metabolite Enzyme
Immunoassay (K960187) |
|----------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The DRI Cocaine
Metabolite Assay is a
homogeneous enzyme
immunoassay intended for
the qualitative and/or semi-
quantitative determination
of benzoylecgonine
(Cocaine Metabolite) in
human urine at a cutoff
concentration of either 150
ng/mL or 300 ng/mL. | This homogeneous cocaine
metabolite enzyme
immunoassay is intended to
be used for qualitative and
semi-quantitative
determination of
benzoylecgonine (cocaine
metabolite) in human urine
with either 300 ng/ml or 150
ng/ml as a cutoff calibrator. |
| Operating
Principle
(Technology) | DRI | Same |
| Measured
Analyte | Benzoylecgonine | Same |
| Test Matrix | Urine | Same |
| Cut-off Levels | 150 ng/mL and 300 ng/mL | Same |
| Methodology | Homogeneous Enzyme
Immunoassay | Same |
| Reagents Form | Liquid ready-to-use. | Same |
| Antibody | Mouse monoclonal
antibodies | Same |
| Storage | 2-8 °C until expiration date | Same |
| Principal
Operator | Trained professionals | Same |
| Calibrator Levels
for Semi-Quant | 5 point calibrator | 3 point calibrator |
F. Test Principle
The DRI Cocaine Metabolite Assay is a homogeneous enzyme immunoassay using ready-touse liquid reagents. The assay uses a specific antibody, which can detect benzoylecgonine in urine. The DRI technology is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the presence of free drug from the sample, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. In the absence of drug from the sample, the specific antibody binds to the drug labeled with G6PDH and the enzyme activity is inhibited. This phenomenon creates a direct relationship between the drug concentration in the urine and the enzyme activity. The enzyme G6PDH activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.
6
G. Summary of Supporting Data
1. Analytical Performance:
Performance is evaluated at the manufacturer's site on the Beckman Coulter AU680 clinical analyzer.
a) Precision
Precision studies were performed in accordance with CLSI Guideline EP05-A3. Samples were prepared by spiking Benzoylecgonine (Cocaine Metabolite) into drug free urine at the cutoff, 25%, 50%, 75% and 100% above and below the cutoff and tested in both qualitative and semi-quantitative modes. Results presented below were generated by testing all samples in replicates of 2, twice per day for 20 days, total n=80. The results for both cutoffs are summarized in the tables below.
| Spiked
Concentration
(ng/mL) | % of Cutoff
(150 ng/mL) | Total Precision (n=80) | |
|------------------------------------|----------------------------|------------------------|-----------------------------------------------|
| | | # of
Determinants | Immunoassay
Results
(Negative/Positive) |
| 0 | -100% | 80 | 80/0 |
| 37.5 | -75% | 80 | 80/0 |
| 75 | -50% | 80 | 80/0 |
| 112.5 | -25% | 80 | 80/0 |
| 150 | 100% | 80 | 22/58 |
| 187.5 | +25% | 80 | 0/80 |
| 225 | +50% | 80 | 0/80 |
| 262.5 | +75% | 80 | 0/80 |
| 300 | +100% | 80 | 0/80 |
Qualitative Study Analysis for 150 ng/mL cutoff
Qualitative Study Analysis for 300 ng/mL cutoff
7
| Spiked | % of Cutoff
(300 ng/mL) | Total Precision (n=80) | |
|--------------------------|----------------------------|------------------------|-----------------------------------------------|
| Concentration
(ng/mL) | | # of
Determinants | Immunoassay
Results
(Negative/Positive) |
| 0 | -100% | 80 | 80/0 |
| 75 | -75% | 80 | 80/0 |
| 150 | -50% | 80 | 80/0 |
| 225 | -25% | 80 | 80/0 |
| 300 | 100% | 80 | 31/49 |
| 375 | +25% | 80 | 0/80 |
| 450 | +50% | 80 | 0/80 |
| 525 | +75% | 80 | 0/80 |
| 600 | +100% | 80 | 0/80 |
Semi-Quantitative Study Analysis for 150 ng/mL cutoff
| Spiked | % of Cutoff
(150 ng/mL) | Total Precision (n=80) | |
|--------------------------|----------------------------|------------------------|-----------------------------------------------|
| Concentration
(ng/mL) | | # of
Determinants | Immunoassay
Results
(Negative/Positive) |
| 0 | -100% | 80 | 80/0 |
| 37.5 | -75% | 80 | 80/0 |
| 75 | -50% | 80 | 80/0 |
| 112.5 | -25% | 80 | 80/0 |
| 150 | 100% | 80 | 19/61 |
| 187.5 | +25% | 80 | 0/80 |
| 225 | +50% | 80 | 0/80 |
| 262.5 | +75% | 80 | 0/80 |
| 300 | +100% | 80 | 0/80 |
Semi-Quantitative Study Analysis for 300 ng/mL cutoff
| Spiked
Concentration
(ng/mL) | % of Cutoff
(150 ng/mL) | Total Precision (n=80) | |
|------------------------------------|----------------------------|------------------------|-----------------------------------------------|
| | | # of
Determinants | Immunoassay
Results
(Negative/Positive) |
| 0 | -100% | 80 | 80/0 |
| 75 | -75% | 80 | 80/0 |
| 150 | -50% | 80 | 80/0 |
| 225 | -25% | 80 | 80/0 |
| 300 | 100% | 80 | 22/58 |
| 375 | +25% | 80 | 0/80 |
8
| Spiked
Concentration
(ng/mL) | % of Cutoff
(150 ng/mL) | Total Precision (n=80) | |
|------------------------------------|----------------------------|------------------------|-----------------------------------------------|
| | | # of
Determinants | Immunoassay
Results
(Negative/Positive) |
| 450 | +50% | 80 | 0/80 |
| 525 | +75% | 80 | 0/80 |
| 600 | +100% | 80 | 0/80 |
b) Spike Recovery
The study was performed for 21 replicates. This study was carried out by testing spiked samples containing Benzoylecgonine (Cocaine Metabolite) at the cutoff calibrator and control levels. The spiked samples were prepared by spiking Benzoylecgonine (Cocaine Metabolite) into drug free urine. Samples were tested in both qualitative and semi-quantitative mode. The qualitative results for both cutoffs are summarized in the tables below.
| Replicates | 112.5 ng/mL
(n=21) | 187.5 ng/mL
(n=21) |
|-----------------|-----------------------|-----------------------|
| 1 | Negative | Positive |
| 2 | Negative | Positive |
| 3 | Negative | Positive |
| 4 | Negative | Positive |
| 5 | Negative | Positive |
| 6 | Negative | Positive |
| 7 | Negative | Positive |
| 8 | Negative | Positive |
| 9 | Negative | Positive |
| 10 | Negative | Positive |
| 11 | Negative | Positive |
| 12 | Negative | Positive |
| 13 | Negative | Positive |
| 14 | Negative | Positive |
| 15 | Negative | Positive |
| 16 | Negative | Positive |
| 17 | Negative | Positive |
| 18 | Negative | Positive |
| 19 | Negative | Positive |
| 20 | Negative | Positive |
| 21 | Negative | Positive |
| Overlap | No | No |
| Relative to C/O | All 21 below C/O | All 21 above C/O |
Qualitative Data for 150 ng/mL cutoff
9
| Replicates | 225 ng/mL
(n=21) | 375 ng/mL
(n=21) |
|-----------------|---------------------|---------------------|
| 1 | Negative | Positive |
| 2 | Negative | Positive |
| 3 | Negative | Positive |
| 4 | Negative | Positive |
| 5 | Negative | Positive |
| 6 | Negative | Positive |
| 7 | Negative | Positive |
| 8 | Negative | Positive |
| 9 | Negative | Positive |
| 10 | Negative | Positive |
| 11 | Negative | Positive |
| 12 | Negative | Positive |
| 13 | Negative | Positive |
| 14 | Negative | Positive |
| 15 | Negative | Positive |
| 16 | Negative | Positive |
| 17 | Negative | Positive |
| 18 | Negative | Positive |
| 19 | Negative | Positive |
| 20 | Negative | Positive |
| 21 | Negative | Positive |
| Overlap | No | No |
| Relative to C/O | All 21 below C/O | All 21 above C/O |
Qualitative Data for 300 ng/mL cutoff
c) Analytical Recovery and Linearity
Linearity studies were performed in accordance with CLSI Guideline EP06-A. To demonstrate the dilution linearity for purposes of sample dilution and quality control of the entire assay range, drug free urine was spiked to the high level calibrator using Benzoylecgonine (Cocaine Metabolite) (1000 ng/mL) and diluted with drug free urine to generate 9 intermediate levels.
Each sample was run in replicates of five in semi-quantitative mode and the average was used to determine percent recovery compared to the expected target value. The percent recovery is summarized in the table below.
| Level | Expected
Concentration
(ng/mL) | Observed
Concentration
(ng/mL) | Recovery (%) |
|-------|--------------------------------------|--------------------------------------|--------------|
| 1 | 0 | 0.6 | N/A |
10
| Level | Expected
Concentration
(ng/mL) | Observed
Concentration
(ng/mL) | Recovery (%) |
|-------|--------------------------------------|--------------------------------------|--------------|
| 2 | 102.5 | 103.6 | 101.1 |
| 3 | 205.0 | 213.6 | 104.2 |
| 4 | 307.5 | 294.8 | 95.9 |
| 5 | 410.0 | 413.8 | 100.9 |
| 6 | 512.5 | 510.4 | 99.6 |
| 7 | 615.0 | 640.6 | 104.2 |
| 8 | 717.5 | 781.4 | 108.9 |
| 9 | 820.0 | 880.0 | 107.3 |
| 10 | 922.5 | 952.0 | 103.2 |
| 11 | 1025.0 | 1025.0 | 100.0 |
d) Method Comparison and Accuracy
The method comparison study was performed in accordance with CLSI Guideline EP09-A3. One hundred patient samples were analyzed by the DRI Cocaine Metabolite Assay in both qualitative and semi-quantitative modes and the results were compared to LC-MS/MS. The overall concordance between LC-MS/MS and DRI Cocaine Metabolite Assay is 100%. The qualitative and semi-quantitative results for both cutoffs are summarized in the tables below.
Semi-Quantitative Mode Accuracy study with LC-MS/MS as reference method for 150 ng/mL cutoff
| Candidate
Device
Results | Negative
by LC-
MS/MS | 225 ng/mL) |
|--------------------------------|-----------------------------|--------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|
| Positive | 0 | 0 | 0 | 6 | 44 |
| Negative | 45 | 0 | 5 | 0 | 0 |
Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100%
11
Semi-Quantitative Mode Accuracy study with LC-MS/MS as reference method for 300 ng/mL cutoff
| Candidate
Device
Results | Negative
by LC-
MS/MS | 450 ng/mL) |
|--------------------------------|-----------------------------|---------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|
| Positive | 0 | 0 | 0 | 6 | 44 |
| Negative | 45 | 0 | 5 | 0 | 0 |
Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100%
Qualitative Accuracy study with LC-MS/MS as reference method for 150 ng/mL cutoff
| Candidate
Device
Results | Negative
by LC-
MS/MS | 225 ng/mL) |
|--------------------------------|-----------------------------|--------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|
| Positive | 0 | 0 | 0 | 6 | 44 |
| Negative | 45 | 0 | 5 | 0 | 0 |
Agreement among Positives: 50/50 = 100% Agreement among Negative: 50/50 = 100%
Qualitative Accuracy study with LC-MS/MS as reference method for 300 ng/mL cutoff
12
| Candidate
Device
Results | Negative
by LC-
MS/MS | 450 ng/mL) |
|--------------------------------|-----------------------------|---------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------|
| Positive | 0 | 0 | 0 | 6 | 44 |
| Negative | 45 | 0 | 5 | 0 | 0 |
Agreement among Positives: 50/50 = 100%
Agreement among Negative: 50/50 = 100%
e) Specificity
The cross-reactivity of Cocaine and its metabolites were evaluated by adding known amounts of each compound to drug-free negative urine. The results are summarized in the tables below.
| Cocaine and metabolites | Tested Concentration
(ng/mL) | Cross-reactivity
(%) |
|--------------------------|---------------------------------|-------------------------|
| Benzoylecgonine | 150 | 100 |
| Cocaine | 25,000 | 0.6 |
| Cocaethylene | 30,000 | 0.5 |
| Ecgonine | 90,000 | 0.17 |
| Ecgonine Methyl Ester | 100,000 |