(396 days)
Not Found
No
The device description and performance studies focus on a competitive immunoassay using fluorescence resonance energy transfer (FRET) and a cutoff calibrator for qualitative results. There is no mention of AI or ML algorithms being used for data analysis, interpretation, or decision-making.
No.
This device is an in vitro diagnostic (IVD) tool used to screen for methamphetamine in oral fluid; it does not directly treat or prevent a medical condition.
Yes
The device is explicitly stated as an "In Vitro Diagnostic competitive immunoassay" in the "Device Description" and its "Intended Use / Indications for Use" states it is used to "perform a qualitative screen for methamine... in neat oral fluid samples". This clearly indicates its purpose is to diagnose the presence of a substance in a biological sample.
No
The device description clearly indicates it is an In Vitro Diagnostic competitive immunoassay involving chemical reagents (fluorophores, antibodies) and a physical measurement of fluorescence resonance energy transfer (FRET). This involves hardware components for the assay and measurement, not just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "For In Vitro Diagnostic Use Only." This is repeated for both the assay and the calibrators/controls.
- Device Description: The "Device Description" section begins by stating: "The RapidFRET Oral Fluid Assay for Methamphetamine is an In Vitro Diagnostic competitive immunoassay..."
- Nature of the Test: The device is designed to test human oral fluid samples in vitro (outside the body) to detect the presence of methamphetamine. This is the core function of an in vitro diagnostic device.
- Intended Use: The intended use is for prescription use in central laboratories to perform a qualitative screen for methamphetamine in oral fluid. This aligns with the typical use of IVD devices in a clinical laboratory setting.
N/A
Intended Use / Indications for Use
The RapidFRET Oral Fluid Assay for Methamphetamine is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for methamine at 50 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.
The RapidFRET Oral Fluid Methamine Calibrators and RapidFRET Oral Fluid Methamphetamine Controls are intended for use only with appropriate RapidFRET Oral Fluid Assay products and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive controls are used to monitor laboratory systems, operators, precision. accuracy and assay conditions. For In Vitro Diagnostic Use Only.
Product codes (comma separated list FDA assigned to the subject device)
LAF, DLJ, LAS
Device Description
The RapidFRET Oral Fluid Assay for Methamphetamine is an In Vitro Diagnostic competitive immunoassay used to detect methamphetamine in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
human oral fluid
Indicated Patient Age Range
Not Found
Intended User / Care Setting
central laboratories
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)
Precision and Analytical Sensitivity:
- Study Type: Analytical Precision and Sensitivity Study
- Sample Size: Each of the 9 concentration levels (0%, 25%, 50%, 75%, 100%, 125%, 150%, 175%, 200% of cutoff) had 264 replicates across 3 lots and 20 non-consecutive days. Total N = 264 * 9 = 2376.
- Key Results:
- For 0%, 25%, 50%, 75% of cutoff, 0 samples were positive (100% negative).
- For 125%, 150%, 175%, 200% of cutoff, 264 samples were positive (100% positive).
- For 100% of cutoff, 47 samples were positive and 217 samples were negative.
- The analytical sensitivity is between 75% and 125% of cutoff, and expected results were achieved at a 100% frequency.
Correlation with MS Quantitation:
- Study Type: Clinical Correlation Study with LC/MS/MS
- Sample Size: n=92 oral fluid samples
- Data Source: Neat oral fluid collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for methamphetamine.
- Key Results:
- Samples with 150% of Cutoff: RapidFRET POS (39), RapidFRET NEG (2).
- Footnotes indicate specific interfering substances in some samples.
Cross Reactivity and Analytical Specificity:
- Study Type: Cross Reactivity and Analytical Specificity Study
- Data Source: A compound library of different structurally related and unrelated compounds including metabolites, OTC and prescription medications and drugs of abuse. Common substances such as foods, dental products, and pH variations were also evaluated.
- Annotation Protocol: Compounds were spiked at 30,000 ng/mL into neat oral fluid pool aliquots with 0 ng/mL, 25 ng/mL and 75 ng/mL methamphetamine equivalent. Compounds giving unexpected results were further titrated to determine cross-reactivity concentration.
- Key Results:
- Twenty structurally related compounds were determined to cross-react below 30,000 ng/mL in the absence of methamphetamine. Examples include (-) Ephedrine (1.0% cross-reactivity), Fenfluramine (17%), l-Methamphetamine (17%), N-methyl-1,3-benzodioxolylbutanamine (MBDB) (179%), Methylenedioxymethamphetamine (MDMA) (40%), para-Methoxymethamphetamine (PMMA) (57%).
- Three structurally related compounds (d-Ephedrine, l-Amphetamine, Procainamide) cross-reacted below 30,000 ng/mL in the presence of 25 ng/mL methamphetamine (all at 0.2% cross-reactivity).
- All evaluated common substances (HSA, ethanol, baking soda, whole blood, hemoglobin, hydrogen peroxide, sodium chloride, cholesterol, denture adhesive, ascorbic acid, bilirubin, IgA, IgG and IgM, and pH variations from 5-9) at listed concentrations gave a NEG result when spiked with 25 ng/mL methamphetamine and a POS result when spiked with 75 ng/mL methamphetamine.
- Oral fluid samples collected after using antiseptic mouthwash, cough syrup, cranberry juice, orange juice, tooth paste, chewing tobacco, cigarettes, chewing gum, hard candy, teeth whitening strips, cola, water, antacid, coffee and tea all gave a NEG result when spiked with 25 ng/mL methamphetamine and a POS result when spiked with 75 ng/mL methamphetamine.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Summary Precision Data shows the following:
- Analytical sensitivity is between 75% and 125% of cutoff.
- Expected results were achieved at a 100% frequency for samples at 0%, 25%, 50%, 75% (all negative) and 125%, 150%, 175%, 200% (all positive).
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.
Lin-Zhi International, Inc., LZI Oral Fluid Methamphetamine Enzyme Immunoassay (K131652)
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
§ 862.3610 Methamphetamine test system.
(a)
Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.(b)
Classification. Class II (special controls). A methamphetamine 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/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. In the center of the seal is a stylized image of three human profiles facing to the right, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
September 18, 2015
BIOPHOR DIAGNOSTICS, INC. NATHANIEL BUTLIN VICE PRESIDENT 1201 DOUGLAS AVENUE REDWOOD CITY CA 94063
Re: K142293
Trade/Device Name: Rapidfret Oral Fluid Assav for Methamphetamine Rapidfret Oral Fluid Methamphetamine Calibrators Rapidfret Oral Fluid Methamphetamine Controls Regulation Number: 21 CFR 862.3610 Regulation Name: Methamphetamine test system Regulatory Class: II Product Code: LAF, DLJ, LAS Dated: September 11, 2015 Received: September 14, 2015
Dear Dr. Butlin:
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, listing 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S
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
Indications for Use
510(k) Number (if known) K142293
Device Name
RapidFRET Oral Fluid Assay for Methamphetamine, RapidFRET Oral Fluid Methamphetamine Calibrators, RapidFRET Oral Fluid Methamphetamine Controls
Indications for Use (Describe)
The RapidFRET Oral Fluid Assay for Methamphetamine is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for methamine at 50 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.
The RapidFRET Oral Fluid Methamine Calibrators and RapidFRET Oral Fluid Methamphetamine Controls are intended for use only with appropriate RapidFRET Oral Fluid Assay products and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive controls are used to monitor laboratory systems, operators, precision. accuracy and assay conditions. 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)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
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:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"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."
3
510(k) Summary for the RapidFRET Oral Fluid Assay for Methamphetamine
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92
September 11, 2015
The assigned 510(k) number is: K142293
807.92(a)(1): Contact Information
- Name: Biophor Diagnostics, Inc. Address: 1201 Douglas Avenue
- Redwood City, CA 94063
Contact: Nathaniel G. Butlin, Ph.D.
- Phone: 650-367-4954
- Fax: 650-364-4985
807.92(a)(2): Device Name, Common Name and Classification
RapidFRET Oral Fluid Assay for Methamphetamine (Methamphetamine Test System) RapidFRET Oral Fluid Methamphetamine Calibrators (Drug Specific Calibrator) RapidFRET Oral Fluid Methamphetamine Controls (Drug Specific Control Materials)
| Product | Code | Class | Regulation
Section | Panel |
|--------------------------------------------------|------|-------|-----------------------|-----------------|
| RapidFRET Oral Fluid Assay for Methamphetamine | LAF | II | 862.3610 | 91 - Toxicology |
| RapidFRET Oral Fluid Methamphetamine Calibrators | DLJ | II | 862.3200 | 91 - Toxicology |
| RapidFRET Oral Fluid Methamphetamine Controls | LAS | I | 862.3280 | 91 - Toxicology |
807.92(a)(3): Identification of Legally Marketed Predicate Devices
Lin-Zhi International, Inc., LZI Oral Fluid Methamphetamine Enzyme Immunoassay (K131652).
807.92(a)(4): Device Description
The RapidFRET Oral Fluid Assay for Methamphetamine is an In Vitro Diagnostic competitive immunoassay used to detect methamphetamine in human oral fluid. This is a ready-to-use homogenous system that involves energy transfer between an acceptor fluorophore labeled to an antibody and a donor fluorophore labeled to drug. The assay is based on competition between drug in the sample and drug labeled with the donor fluorophore for a fixed number of binding sites on the antibody reagent. When acceptor and donor fluorophores are brought into close proximity through a binding event, energy transfer occurs. The fluorescence resonance energy transfer (FRET) signal is measured at the wavelength of the acceptor fluorophore and is inversely proportional to the amount of drug in the sample. A
4
Cutoff Calibrator is used to translate the sample measurement into a positive or negative result. Controls are used to establish and monitor precision and accuracy.
807.92(a)(5): Intended Use
The RapidFRET Oral Fluid Assay for Methamphetamine is a homogeneous time-resolved fluorescence assay that is intended for prescription use in central laboratories only on the RapidFRET Integrated Workstation. The assay is used to perform a qualitative screen for Methamphetamine at 50 ng/mL in neat oral fluid samples collected with the RapidEASE Oral Fluid Collector. This assay provides only a preliminary result. To obtain a confirmed analytical result, a more specific alternate chemical method such as GC/MS or LC/MS/MS is required. Professional judgment should be applied to any drug test result, particularly when using preliminary positive results. For In Vitro Diagnostic Use Only.
The RapidFRET Oral Fluid Methamphetamine Calibrators and RapidFRET Oral Fluid Methamphetamine Controls are intended for use only with appropriate RapidFRET Oral Fluid Assay Products and samples collected with the RapidEASE Oral Fluid Collector. The cutoff calibrator is used to determine the cutoff level and translate the assay measurement into a positive or negative result. The positive and negative controls are used to monitor laboratory systems, operators, precision, accuracy and assay conditions. For In Vitro Diagnostic Use Only.
| | Candidate Device
(RapidFRET MET) | Predicate Device
(Lin-Zhi MET, K131652) |
|--------------------------------|------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------|
| Indications for
Use | Qualitative determination of
methamphetamine in human oral fluid in
clinical setting. | Qualitative determination of
methamphetamine in human oral fluid in
clinical setting. |
| Methodology | Competitive homogeneous
immunoassay. | Competitive homogeneous
immunoassay. |
| Kit
Components | 1 Drug specific antibody reagent in liquid,
ready to use format.
1 Drug conjugate reagent in liquid, ready
to use format. | A drug specific antibody reagent (R1) and
a drug conjugate reagent (R2). |
| Performance
Characteristics | Precision, accuracy, cross
reacting/interfering studies demonstrate
equivalence to the predicate device. | Precision, accuracy, cross
reacting/interfering studies are similar to
the RapidFRET Oral Fluid Assay for
Methamphetamine. |
| Safety and | Demonstrated in bench testing and | Demonstrated in bench testing and |
807.92(a)(6): Technological Similarities and Differences to the Predicate
5
| | Candidate Device
(RapidFRET MET) | Predicate Device
(Lin-Zhi MET, K131652) |
|--------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Effectiveness | described in PI, equivalent to predicate. | described in PI. |
| Neat Oral Fluid
Cutoff Level | 50 ng/mL neat oral fluid. | 50 ng/mL neat oral fluid. |
| Platform | RapidFRET Integrated Workstation
available exclusively from Biophor
Diagnostics, Inc. | MGC240 analyzer |
| Sample
Collection | Neat oral fluid is collected with the
RapidEASE Oral Fluid Collector via direct
expectoration. No diluent is used and
sample is stored in glass sample tube
with inert screw cap. | Oral fluid is collected with the LZI Oral
Fluid collector. |
| Principle and
Procedure | Drugs in the oral fluid sample compete
with the drug conjugate donor
fluorophore for a fixed number of binding
sites on the individual drug antibody
acceptor reagents. When acceptor and
donor fluorophores are brought into
close proximity, through the binding
event, fluorescent energy transfer is
measured.
The amount of drug in the specimen
sample is inversely proportional to the
assay signal as measured by time
resolved fluorescence. | The assay is based on competition of
drugs in a sample and drug labeled
G6PDH. Drug in the sample binds to the
drug specific antibody leaving G6PDH
active to produce assay signal. If no drug
is present in sample, it binds to the
labeled G6PDH enzyme inhibiting activity.
The amount of drug in the specimen is
proportional to the assay signal as
measured by absorbance. |
| Controls and
Calibrator
Levels | Calibrators are available at effective
concentrations of 0 ng/mL and 50 ng/mL.
Controls are available at effective
concentrations of 25 ng/mL and 75
ng/mL. | Calibrators are available at 0 ng/mL, 20
ng/mL, 50 ng/mL, 100 ng/mL and 140
ng/mL. Controls are available at 37.5
ng/mL and 62.5 ng/mL. |
807.92(b)(1): Brief Description of Study Data:
A series of studies were performed that evaluated the device performance characteristics including precision and analytical sensitivity, correlation with LC/MS/MS, cross reactivity, and analytical specificity that are summarized below.
Precision and Analytical Sensitivity
Three lots of the RapidFRET Oral Fluid Assay for Methamphetamine were analyzed for a minimum of 20 non-consecutive days. Negative oral fluid was spiked with dmethamphetamine to 0%, 25%, 50%, 75%, 100%, 125%, 175% and 200% of the cutoff level corresponding to approximately 0, 12.5, 25, 37.5, 50, 62.5, 75, 87.5 and 100 ng/mL. Samples were then processed through a RapidEASE Oral Fluid Collector. Three lots of reagents were used to analyze samples on the RapidFRET Integrated Workstation. The
6
| Summary Precision Data – 3 Lots | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| 0% | 25% | 50% | 75% | 100% | 125% | 150% | 175% | 200% | |
| POS | 0 | 0 | 0 | 0 | 47 | 264 | 264 | 264 | 264 |
| NEG | 264 | 264 | 264 | 264 | 217 | 0 | 0 | 0 | 0 |
| N | 264 | 264 | 264 | 264 | 264 | 264 | 264 | 264 | 264 |
aggregate data is summarized in the tables below:
The data indicate that the analytical sensitivity is between 75% and 125% of cutoff, and expected results were achieved at a 100% frequency.
Correlation with MS Quantitation
Neat oral fluid was collected with the RapidEASE Oral Fluid Collection Device from volunteers potentially positive and negative for methamphetamine. The samples (n=92) were randomized and blinded to the instrument operator and assayed using RapidFRET MET reagents. Following screening, positive and negative samples were sent for confirmatory testing. The summarized data are shown below.
| Accuracy Summary Data | ||||
|---|---|---|---|---|
| Range | 150% of Cutoff | |||
| RapidFRET POS | 8+ | 2‡ | 5 | 39 |
| RapidFRET NEG | 33 | 3 | 0 | 2* |
†Six samples contained MDMA at 241, 1940, 211, 2020, 4310, and 250 ng/mL; a seventh sample contained MDMA at 10 ng/mL, methylone at 47,000 ng/mL and 4-methethylcathinone at 7,240 ng/mL; the eighth sample contained MDMA at 13.6 ng/mL, and methylone at 8,920 ng/mL. +One sample contained MET at 40.4 ng/mL and MDMA at 1,880 ng/mL; a second sample contained MET at 36.8 ng/mL and MDMA at 439 ng/mL. *One sample contained 150 ng/mL I-methamphetamine; a second sample contained 28.4 ng/mL d-methamphetamine and 114 ng/mL l-methamphetamine.
Cross Reactivity and Analytical Specificity
A compound library of different structurally related and unrelated compounds including metabolites, OTC and prescription medications and drugs of abuse was used to evaluate the device cross reactivity and specificity. Compounds were spiked at 30,000 ng/mL into neat oral fluid pool aliquots with 0 ng/mL, 25 ng/mL and 75 ng/mL methamphetamine equivalent, processed with the RapidEASE Collector, and tested with the RapidFRET MET assay. Those compounds that gave an unexpected result were further titrated to determine the concentration at which the cross-reacting compound yielded a result approximately equivalent to the cutoff. Twenty (20) structurally related compounds were determined to cross-react below 30,000 ng/mL in the absence of methamphetamine with 3 cross-reacting below 30,000 ng/mL in the presence of 25 ng/mL methamphetamine.
| Structurally Related Cross Reactants | ||
|---|---|---|
| Compound | Cutoff Equivalent | |
| Concentration (ng/mL) | Percent Cross-Reactivity | |
| Structurally Related Compounds That Cross React in Neat Oral Fluid Pool with No Added Methamphetamine | ||
| (-) Ephedrine | 5,100 | 1.0% |
7
Biophor Diagnostics, Inc.
Traditional Premarket Notification 510(k) Submission RapidFRET Oral Fluid Assay for Methamphetamine
| Structurally Related Cross Reactants | ||
|---|---|---|
| Compound | Cutoff Equivalent | |
| Concentration (ng/mL) | Percent Cross-Reactivity | |
| Benzodioxolylbutanamine (BDB) | 16,000 | 0.3% |
| Phenethylamine | 5,700 | 0.9% |
| Chloroquine | 2,300 | 2.2% |
| d-Amphetamine | 3,500 | 1.4% |
| Fenfluramine | 290 | 17% |
| I-Methamphetamine | 300 | 17% |
| I-Phenylephrine | 9,400 | 0.5% |
| N-methyl-1,3-benzodioxolylbutanamine (MBDB) | 28 | 179% |
| Methylenedioxyamphetamine (MDA) | 12,700 | 0.4% |
| Methylenedioxyethamphetamine (MDEA) | 1,100 | 4.5% |
| Methylenedioxymethamphetamine (MDMA) | 126 | 40% |
| Mephentermine | 1,500 | 3.3% |
| 4-Methylethcathinone (4-MEC) | 4,555 | 1.1% |
| Methylone | 3,438 | 1.5% |
| para-Methoxyamphetamine (PMA) | 9,100 | 0.5% |
| para-Methoxymethamphetamine (PMMA) | 87 | 57% |
| Procaine | 24,000 | 0.2% |
| Ranitidine | 8,300 | 0.6% |
| Trimethobenzamide | 730 | 6.8% |
| Structurally Related Compounds That Cross React in Oral Fluid Pool Spiked with 25 ng/mL Methamphetamine | ||
| d-Ephedrine | 23,000 | 0.2% |
| I-Amphetamine | 25,000 | 0.2% |
| Procainamide | 23,000 | 0.2% |
A second study evaluated common substances such as foods and dental products as well as pH variations. HSA, ethanol, baking soda, whole blood, hemoglobin, hydrogen peroxide, sodium chloride, cholesterol, denture adhesive, ascorbic acid, bilirubin, lgA, lgG and IgM were spiked into neat oral fluid pool aliquots that contained either 25 ng/mL or 75 ng/mL of methamphetamine equivalent. Neat oral fluid pool was titrated to pH values of 5, 6, 7, 8 and 9, spiked with methamphetamine to 25 ng/mL or 75 ng/mL equivalent and assayed with the RapidFRET MET Assay. The effects of antiseptic mouthwash, cough syrup, cranberry juice, orange juice, tooth paste, chewing tobacco, cigarettes, chewing gum, hard candy, teeth whitening strips, cola, water, antacid, coffee and tea were evaluated by asking volunteers to use a specific item and provide an oral fluid sample. These samples were then spiked with methamphetamine to 25 ng/mL or 75 ng/mL equivalent, processed with RapidEASE Collectors and assayed with the RapidFRET MET device. All compounds at the listed concentrations gave a NEG result when spiked with 25 ng/mL methamphetamine and a POS result when spike with 75 ng/mL methamphetamine.
807.92(b)(3): Conclusions
8
The RapidFRET Oral Fluid Assay for Methamphetamine including the RapidFRET Oral Fluid Methamphetamine Calibrators, the RapidFRET Oral Fluid Methamphetamine Controls and the RapidEASE Oral Fluid Collector were determined to be safe and effective for their intended use.