(290 days)
The CEDIA® Methamphetamine OFT Assay is intended for use in the qualitative detection of methamphetamine at a cutoff concentration of 120.0 ng/mL in neat oral fluid. The specimen must be collected exclusively with the Oral-Eze™ Saliva Collection System. The assay is calibrated against d-methamphetamine and performed on the MGC 240. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA Methamphetamine OFT Calibrators are intended for use in the calibration of d-Methamphetamine when used with the CEDIA Methamphetamine OFT Assay for human oral fluid samples collected with the Oral-Eze™ Saliva Collection System. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA Methamphetamine OFT Assay provides only a preliminary analytical test result. A more specific alternative method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result particularly when preliminary positive results are used.
The CEDIA® Methamphetamine OFT Assay uses recombinant DNA technology to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments i.e., enzyme acceptor (EA) and enzyme donor (ED). These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically.
In the assay, analyte in the sample competes with analyte conjugated to one inactive fragment of ß-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are directly proportional to the amount of drug present in the sample.
The Oral-Eze™ Saliva Collection System consists of Oral-Eze™ saliva collector and collection tube with preservative buffer. Oral-Eze™ saliva collector consists of an absorbent pad attached to a plastic handle. The saliva collector is provided with a volume adequacy indicator. The plastic handle has a round window where blue color will appear when sufficient volume of oral fluid is collected. Samples are collected by placing the collector pad and plastic shield between lower cheek and gum with the plastic shield facing the cheek. Oral fluid collection is done when blue color appears in the window of the handle. The pad is ejected in to the collection tube by placing thumb on the ridges on the handle and pushing the thumb forward. The collection tube is capped and sent to the laboratory for processing and testing.
Here's an analysis of the acceptance criteria and study details for the CEDIA® Methamphetamine OFT Assay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary doesn't explicitly state "acceptance criteria" in a quantitative format as might be found for imaging devices. Instead, it presents performance characteristics that implicitly serve as the basis for demonstrating substantial equivalence. The key performance metrics are related to accuracy (concordance, sensitivity, specificity) against a reference method (GC/MS).
| Acceptance Criteria (Implied) | Reported Device Performance (CEDIA® Methamphetamine OFT Assay) |
|---|---|
| High overall concordance with GC/MS | 98.8% overall concordance with GC/MS |
| High sensitivity compared to GC/MS | 97.6% sensitivity compared to GC/MS |
| High specificity compared to GC/MS | 100.0% specificity compared to GC/MS |
| Accurate classification of samples below cutoff (negative) | Samples below cutoff read as negative |
| Accurate classification of samples above cutoff (positive) | Samples above cutoff read as positive |
| Low control samples classified as negative | Low control samples recovered as negative |
| High control samples classified as positive | High control samples recovered as positive |
| No significant interference from endogenous/exogenous substances | No significant interference observed |
| No significant cross-reactivity with unrelated compounds | No significant cross-reactivity observed |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set: The document does not explicitly state the total number of individual patient samples used in the "Method Comparison" study that determined concordance, sensitivity, and specificity. It only states "The overall concordance between the CEDIA® Methamphetamine OFT Assay and GC/MS is 98.8%." Without the raw numbers of true positives, true negatives, false positives, and false negatives, the exact sample size cannot be determined from this summary.
- Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. It implies the data was collected for the purpose of this submission (likely prospective data collection in a laboratory setting).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- This device is an in vitro diagnostic (IVD) assay, not an imaging AI device that relies on human interpretation for ground truth.
- The ground truth in this context is established by the Gas Chromatography/Mass Spectrometry (GC/MS) method. This is an objective, analytical gold standard for substance identification and quantification. Therefore, human experts are not directly involved in establishing the "ground truth" for individual test samples, though expert technicians operate and validate the GC/MS instruments.
4. Adjudication Method for the Test Set
- Not applicable. As noted above, the ground truth is established by an objective analytical method (GC/MS), not by human interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a "Multi-Reader Multi-Case (MRMC)" comparative effectiveness study was not done. This type of study design is typically used for medical imaging devices where human readers interpret images, and the AI's effect on their performance is being evaluated. This device is an automated IVD assay, not an AI for image interpretation.
6. Standalone Performance
- Yes, a standalone performance study was done. The "Method Comparison" section directly evaluates the CEDIA® Methamphetamine OFT Assay's performance (concordance, sensitivity, specificity) against the GC/MS reference method. This is a measure of the algorithm's (assay's) performance without human-in-the-loop interaction for interpretation, beyond standard laboratory procedures for running the assay.
7. Type of Ground Truth Used
- The ground truth used is objective analytical data from Gas Chromatography/Mass Spectrometry (GC/MS). The summary also mentions Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) as another preferred confirmatory method. These methods are considered the gold standard for drug detection and quantification.
8. Sample Size for the Training Set
- The document does not explicitly state a "training set" size. For an IVD assay like this, the development process involves extensive analytical validation, including testing numerous samples to establish linearity, precision, interference, cross-reactivity, and cutoff optimization. However, it's not typically described in terms of a "training set" like a machine learning model. The various studies (Qualitative Precision, Qualitative Cutoff Characterization, Interference, Specificity and Cross-Reactivity, Method Comparison) collectively represent the data used to characterize and validate the assay's performance.
9. How Ground Truth for the Training Set Was Established
-
For the development and optimization of such an assay, ground truth would be established through:
- Known concentrations: Samples spiked with precise, known concentrations of methamphetamine and its metabolites.
- GC/MS or LC-MS/MS confirmation: Samples from real-world scenarios would be confirmed by gold-standard analytical methods (GC/MS or LC-MS/MS) to establish their true status (positive/negative and concentration).
- Reference materials: Use of certified reference materials and calibrators with established values.
The summary does not detail the specific methodology for establishing ground truth during the assay's development (what would functionally be analogous to a "training set" in AI development), but it implies standard IVD development practices involving these types of validated samples.
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510K SUMMARY
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
The assigned 510(k) number is: K101753
Company/Contact person
APR - 8 2011
Lisa Charter Manager, Regulatory Affairs Thermo Fisher Scientific, Clinical Diagnostic Division 46360 Fremont Blvd Fremont, CA 94538 Phone: (510) 979-5142 Facsimile: (510) 979-5422 Email: Lisa.Charter@ThermoFisher.com
Date Prepared: April 4, 2011
Regulatory Declarations
| Common / Usual Name | CEDIA® Methamphetamine OFT Assay |
|---|---|
| CEDIA® Methamphetamine OFT Calibrators | |
| Trade/ Proprietary Name | Thermo Scientific CEDIA® Methamphetamine OFT Assay |
| Thermo Scientific CEDIA® Methamphetamine OFT | |
| Calibrators | |
| Classification Regulations | 21 CFR 862.3610 |
| 21 CFR 862.3200 | |
| Device Class | Class II |
| Device Regulation Panel | Toxicology |
| Product Codes | LAF, DLJ |
Intended use
The CEDIA® Methamphetamine OFT Assay is intended for use in the qualitative detection of methamphetamine at a cutoff concentration of 120.0 ng/mL in neat oral fluid. The specimen must be collected exclusively with the Oral-Eze™ Saliva Collection System. The assay is calibrated against d-methamphetamine and performed on the MGC 240. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA Methamphetamine OFT Calibrators are intended for use in the calibration of d-Methamphetamine when used with the CEDIA Methamphetamine OFT Assay for human oral fluid samples collected with the Oral-Eze™ Saliva Collection System. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA Methamphetamine OFT Assay provides only a preliminary analytical test result. A more specific alternative method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result particularly when preliminary positive results are used.
Conditions for use
The CEDIA® Methamphetamine OFT Assay is for prescription professional use only in clinical chemistry laboratories. It is not for use in Point of Care settings.
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Legally marketed device to which equivalency is claimed
CEDIA® Methamphetamine OFT Assay is substantially equivalent to the previously cleared STC Methamphetamine Intercept® MICRO-PLATE EIA, K993208 (At present OT), OraSure Technologies Inc.)
DESCRIPTION OF DEVICE
CEDIA® Methamphetamine OFT Assay
The CEDIA® Methamphetamine OFT Assay uses recombinant DNA technology to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments i.e., enzyme acceptor (EA) and enzyme donor (ED). These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically.
In the assay, analyte in the sample competes with analyte conjugated to one inactive fragment of ß-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are directly proportional to the amount of drug present in the sample.
Principle of Oral-Eze™ Saliva Collection System
The Oral-Eze™ Saliva Collection System consists of Oral-Eze™ saliva collector and collection tube with preservative buffer. Oral-Eze™ saliva collector consists of an absorbent pad attached to a plastic handle. The saliva collector is provided with a volume adequacy indicator. The plastic handle has a round window where blue color will appear when sufficient volume of oral fluid is collected. Samples are collected by placing the collector pad and plastic shield between lower cheek and gum with the plastic shield facing the cheek. Oral fluid collection is done when blue color appears in the window of the handle. The pad is ejected in to the collection tube by placing thumb on the ridges on the handle and pushing the thumb forward. The collection tube is capped and sent to the laboratory for processing and testing.
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Comparison of Technological Characteristics
.
The CEDIA® Methamphetamine OFT Assay is substantially equivalent to the OTI Methamphetamine Intercept® MICRO-PLATE EIA. (K993208)
| Comparison | Subject DeviceCEDIA® Methamphetamine OFT Assay | Predicate DeviceOTI Methamphetamine Intercept® MICRO-PLATE EIAK993208 |
|---|---|---|
| Intended Use | The CEDIA® Methamphetamine OFT Assay is intended for use in the qualitative detection of methamphetamine at a cutoff concentration of 120.0 ng/mL in neat oral fluid. The specimen must be collected exclusively with the Oral-Eze™ Saliva Collection System. The assay is calibrated against d-methamphetamine and performed on the MGC 240. This in vitro diagnostic device is intended for clinical laboratory use only.The CEDIA Methamphetamine OFT Calibrators are intended for use in the calibration of d-Methamphetamine when used with the CEDIA Methamphetamine OFT Assay for human oral fluid samples collected with the Oral-Eze™ Saliva Collection System. This in vitro diagnostic device is intended for clinical laboratory use only.The CEDIA Methamphetamine OFT Assay provides only a preliminary analytical test result. A more specific alternative method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result particularly when preliminary positive results are used. | The OTI Methamphetamine Intercept® MICRO-PLATE EIA is intended for use in the qualitative determination of methamphetamine in oral fluid collected with the Intercept Drugs of Abuse (DOA) Oral Specimen Collection Device. For In Vitro Diagnostic Use. |
| TestPrinciple | Microgenics CEDIA® Methamphetamine OFT Assay uses recombinant DNA technology to produce a unique homogeneous enzyme immunoassay system (5) | The OTI Methamphetamine Intercept® MICRO-PLATE EIA is a competitive immunoassay for the detection of methamphetamine in oral fluid collected with the Intercept® Oral Specimen Collection |
| enzyme β-galactosidase, which hasbeen genetically engineered intotwo inactive fragments. Thesefragments spontaneously re-associate to form fully activeenzyme that, in the assay format,cleave a substrate, generating acolor change that can be measuredspectrophotometrically.In the assay, analyte in the samplecompetes with analyte conjugated toone inactive fragment (enzymedonor) of β-galactosidase forantibody binding site. If analyte ispresent in the sample, it binds toantibody, leaving the inactiveenzyme fragment free to form activeenzyme. If the analyte is not presentin the sample, antibody binds toanalyte conjugated on the inactivefragment, inhibiting the re-association of inactive β-galactosidase fragments, and noactive enzyme is formed. Theamount of active enzyme formedand resultant absorbance changeare directly proportional to theamount of analyte present in thesample. | Device. Specimen or standard isadded to an EIA well in combinationwith an enzyme -labeled haptenderivative. In an EIA well containingan oral fluid specimen positive forcocaine or cocaine metabolites,there is a competition betweencocaine and/or cocaine metaboliteand the enzyme labeled hapten tobind to the antibody fixed onto theEIQ well. EIA wells are thenwashed, substrate is added, andcolor is produced. The absorbancemeasured at 450 nm is inverselyproportional to the amount ofcocaine or cocaine metabolitepresent in the specimen or calibrator/ control. | |
| SampleMatrix | Oral Fluid | Oral Fluid |
| Calibratorlevels | 0, 40, 200 ng/mL | 0 and 40 ng/mL |
| Cutoff level | 120 ng/mL in neat oral fluid | 40 ng/mL |
| UnassayedControllevels | 20 and 60 ng/mL | 20 and 80 ng/mL |
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SUMMARY OF CLINICAL TESTING
Qualitative Precision
All samples tested recovered accurately. Samples at levels below the cutoff read as negative and samples at levels above the cutoff read as positive.
Qualitative Cutoff Characterization
All samples tested recovered accurately, low control as negative and high control level as positive.
Interference
Results demonstrated that there was no significant interference from endogenous and exogenous substances in oral fluid at the tested concentrations and in samples adjusted to pH range of 5 to 9.
Specificity and Cross-Reactivity
Cross-reactivity to metabolites and structurally related compounds was tested in the assay. No significant cross-reactivity was observed with other structurally unrelated compounds.
Method Comparison
The overall concordance between the CEDIA® Methamphetamine OFT Assay and GC/MS is 98.8%. The comparison of sample results by the CEDIA® Methamphetamine OFT Assay to GC/MS showed 97.6% sensitivity and 100.0% specificity.
Conclusion
As summarized, the CEDIA® Methamphetamine OFT Assay is substantially equivalent to the OTI Methamphetamine Metabolite Intercept® MICRO-PLATE ElA. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied.
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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an image of a stylized eagle or bird symbol.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
Microgenics Corp. c/o Lisa Charter 46360 Fremont Blvd. Fremont, CA 94538
APR 0 8 2011
Re: K101753
Trade Name: Thermo Scientific CEDIA Methamphetamine OFT Assay and Thermo Scientific CEDIA Methamphetamine OFT Calibrators Regulation Number: 21 CFR 862.3610 Regulatory Class: II Product Codes: LAF, DLJ Dated: March 10, 2011 Received: March 14, 2011
Dear Ms. Charter:
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.
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 can be found in Title 21, Code of Federal Regulations (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 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 Small Manufacturers, International and Consumer Assistance at its toll from mber (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
CJC.
Courtney Harper, Ph.D. 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
510(k) Number (if known): K101753
Device Name: CEDIA® Methamphetamine OFT Assay CEDIA® Methamphetamine OFT Calibrators
Indications for Use:
The CEDIA® Methamphetamine OFT Assay is intended for use in the qualitative detection of methamphetamine at a cutoff concentration of 120.0 ng/mL in neat oral fluid. The specimen must be collected exclusively with the Oral-Eze™ Saliva Collection System. The assay is calibrated against d-methambhetamine and performed on the MGC 240. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA Methamphetamine OFT Calibrators are intended for use in the calibration of d-Methamphetamine when used with the CEDIA Methamphetamine OFT Assay for human oral fluid samples collected with the Oral-Eze™ Saliva Collection System. This in vitro diagnostic device is intended for clinical laboratory use only.
The CEDIA Methamphetamine OFT Assay provides only a preliminary analytical test result. A more specific alternative method must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) and Liguid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result particularly when preliminary positive results are used.
Prescription Use × (21 CFR Part 801 Subpart D)
And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Cawlf Benson
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K101753
§ 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).