The CEDIA® Amphetamine OFT Assay is intended for use in the qualitative determination of amphetamine in human oral fluid at a cutoff concentration of 150 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-amphetamine and performed on the MGC 240. This in vitro diagnostic device is intended for clinical laboratory use only.

The CEDIA Amphetamine 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 anv drug of abuse test result particularly when preliminary positive results are used.

Device Description

The CEDIA® Amphetamine OFT Assay uses recombinant DNA technology to produce a unique homogeneous enzyme immunoassay system. The assay is based on the bacterial enzyme ßgalactosidase, 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-qalactosidase 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 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.

AI/ML Overview

This document describes the performance testing and acceptance criteria for the CEDIA® Amphetamine OFT Assay.

1. Table of Acceptance Criteria and Reported Device Performance:

Acceptance Criteria Category	Acceptance Criteria	Reported Device Performance
Qualitative Precision	Samples below cutoff should read negative. Samples above cutoff should read positive.	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	Low control should read negative. High control should read positive.	All samples tested recovered accurately, low control as negative and high control level as positive.
Interference	No significant interference from endogenous and exogenous substances in oral fluid at tested concentrations and in samples adjusted to pH range of 5 to 9.	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	No significant cross-reactivity with structurally unrelated compounds.	No significant cross-reactivity was observed with other structurally unrelated compounds. Cross-reactivity to metabolites and structurally related compounds was tested.
Method Comparison (Concordance with GC/MS)	100% concordance with GC/MS.	The overall concordance between the CEDIA® Amphetamine OFT Assay and GC/MS is 100.0%.
Method Comparison (Sensitivity)	100% sensitivity compared to GC/MS.	The comparison of sample results by the CEDIA® Amphetamine OFT Assay to GC/MS showed 100.0% sensitivity.
Method Comparison (Specificity)	100% specificity compared to GC/MS.	The comparison of sample results by the CEDIA® Amphetamine OFT Assay to GC/MS showed 100.0% specificity.

2. Sample Size Used for the Test Set and Data Provenance:

The document does not explicitly state the specific sample sizes used for each of the performance tests (Qualitative Precision, Qualitative Cutoff Characterization, Interference, Specificity and Cross-Reactivity, and Amphetamine Method Comparison).

The data provenance is not explicitly stated in terms of country of origin. However, the device is intended for clinical laboratory use, implying that the samples would typically originate from such settings. The nature of the tests (e.g., "samples at levels below the cutoff," "samples at levels above the cutoff," "endogenous and exogenous substances") suggests controlled laboratory experiments, and potentially spiked or characterized samples, rather than purely retrospective or prospective collection of patient samples. For the Amphetamine Method Comparison, "sample results" are compared to GC/MS, implying collected samples, but the source (e.g., clinical specimens, spiked controls) is not detailed.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts:

The document does not mention the use of experts to establish ground truth in the traditional sense of human interpretation for image-based or diagnostic decisions. For the Amphetamine Method Comparison, the ground truth is established by Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), which are considered the "preferred confirmatory methods." These are objective analytical methods, not human expert consensus.

4. Adjudication Method for the Test Set:

Not applicable. The ground truth for the method comparison is based on objective analytical techniques (GC/MS, LC-MS/MS), not human interpretation requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

Not applicable. This is an in vitro diagnostic device (an assay for chemical analysis), not an AI-assisted diagnostic tool that would involve human readers or interpreters.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:

Yes, the performance data presented is for the device operating in a standalone capacity (algorithm/assay only). The results of the CEDIA® Amphetamine OFT Assay are directly compared to the confirmatory methods (GC/MS), without any human interpretation of the assay's primary output affecting the reported performance metrics. The assay provides a "preliminary analytical test result" which then requires confirmed with a "more specific alternative method."

7. The Type of Ground Truth Used:

The primary ground truth used for performance validation, specifically in the "Amphetamine Method Comparison," is Gas Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). These are highly accurate and specific analytical techniques considered the gold standard for drug confirmation.

8. The Sample Size for the Training Set:

Not applicable. This product is a chemical assay, not a machine learning or AI algorithm that requires a training set in the typical sense. The assay's "training" or development would involve laboratory optimization and validation using chemical principles and reference materials, rather than a data-driven training set used for AI.

9. How the Ground Truth for the Training Set was Established:

Not applicable, as there is no training set in the context of a machine learning algorithm. The assay's development and parameters would be established through standard analytical chemistry practices, using known concentrations of analytes and reference standards.

Summary

{0}------------------------------------------------

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: K101745

Company/Contact person

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

February 14, 2011

Requlatory Declarations

Common / Usual Name	CEDIA® Amphetamine OFT Assay
Trade/ Proprietary Name	Thermo CEDIA® Amphetamine OFT Assay
Classification Regulation	21 CFR 862.3100
Device Class	Class II
Device Regulation Panel	Toxicology
Product Code	DKZ

Intended use

{1}------------------------------------------------

Conditions for use

The CEDIA® Amphetamine OFT Assay is for prescription professional use only in clinical chemistry laboratories. It is not for use in Point of Care settings.

Legally marketed device to which equivalency is claimed

CEDIA® Amphetamine OFT Assay is substantially equivalent to the previously cleared Immunalysis Amphetamine ELISA for Oral Fluids (K051579).

DESCRIPTION OF DEVICE

Principle of the CEDIA® Amphetamine OFT Assay

Principle of Oral-Eze™ Saliva Collection System

{2}------------------------------------------------

Comparison of Technological Characteristics

CEDIA® Amphetamine OFT Assay is substantially equivalent to the previously cleared Immunalysis Amphetamine ELISA for Oral Fluids (K051579).

Comparison	Proposed DeviceCEDIA® Amphetamine OFT Assay	Predicate DeviceImmunalysis Amphetamine ELISAfor Oral Fluids, K051579
Indicationsfor Use	The CEDIA® Amphetamine OFTAssay is intended for use in thequalitative determination ofamphetamine in human oral fluid ata cutoff concentration of 150 ng/mLin neat oral fluid. The specimenmust be collected exclusively withthe Oral-Eze™ Saliva CollectionSystem. The assay is calibratedagainst d-amphetamine andperformed on the MGC 240. This invitro diagnostic device is intendedfor clinical laboratory use only.The CEDIA Amphetamine OFTAssay provides only a preliminaryanalytical test result. A more specificalternative method must be used toobtain a confirmed analytical result.Gas Chromatography/MassSpectrometry (GC/MS) and LiquidChromatography-Tandem MassSpectrometry (LC-MS/MS) are thepreferred confirmatory methods.Clinical consideration andprofessional judgment should beapplied to any drug of abuse testresult particularly when preliminarypositive results are used.	The Immunalysis AmphetamineELISA test system utilizes anEnzyme Linked Immunoassay(ELISA) for the qualitative detectionof Amphetamine in oral fluidsamples collected with theQuantisal™ oral fluid collectiondevice using a cutoff of 50 ng/mL ofd-Amphetamine. This in-vitrodiagnostic device is intended forclinical laboratory use only.The Immunalysis AmphetamineELISA Kit for Oral Fluids providesonly a preliminary analytical restresult. A more specific alternatechemical method must be used inorder to obtain a confirmedanalytical result. Gaschromatography/mass spectrometry(GC/MS) is the preferredconfirmatory method. Clinical andProfessional judgment should beapplied to any drug of abuse testresult, particularly when preliminarypositive results are used.
TestPrinciple	The CEDIA® Amphetamine OFTAssay uses recombinant DNAtechnology to produce a uniquehomogeneous enzymeimmunoassay system. The assay isbased on the bacterial enzyme ß-galactosidase, which has beengenetically engineered into twoinactive fragments i.e., enzymeacceptor (EA) and enzyme donor(ED). These fragmentsspontaneously reassociate to formfully active enzyme that, in theassay format cleaves a substrate	Enzyme-labeled drug and drugpresent in the sample compete forlimited antibody binding sites.Binding of the enzyme-labeled druginhibits its reaction with thesubstrate, thereby influencing therate of absorbance changemeasured by the instrument. Therate of absorbance change isproportional to the concentration ofdrug in the sample. Concentrationsof controls and unknowns arecalculated from the standard curve.Results are read at 450 and 620
	generating a color change that canbe measuredspectrophotometrically.In the assay, analyte in the samplecompetes with analyte conjugated toone inactive fragment of β-galactosidase for antibody bindingsite. If analyte is present in thesample, it binds to antibody, leavingthe inactive enzyme fragments freeto form active enzyme. If analyte isnot present in the sample, antibodybinds to analyte conjugated on theinactive fragment, inhibiting thereassociation of inactive β-galactosidase fragments, and noactive enzyme is formed. Theamount of active enzyme formedand resultant absorbance changeare directly proportional to theamount of drug present in thesample.	nm.
SampleMatrix	Oral Fluid	Oral Fluid
Cutoff value	150 ng/mL in neat oral fluid	200 ng/ml in neat oral fluid50 ng/ml diluted sample
Calibratorlevels	0, 50, 200 ng/mL	50 ng/mL
Cutoff level	50 ng/mL	50 ng/mL
UnassayedControllevels	25, 75 ng/mL	25, 100 ng/mL

{3}------------------------------------------------

SUMMARY OF PERFORMANCE 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.

{4}------------------------------------------------

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.

Amphetamine Method Comparison

The overall concordance between the CEDIA® Amphetamine OFT Assay and GC/MS is 100.0%. The comparison of sample results by the CEDIA® Amphetamine OFT Assay to GC/MS showed 100.0% sensitivity and 100.0% specificity.

Conclusion

As summarized, the CEDIA® Amphetamine OFT Assay is substantially equivalent to the Immunalysis Amphetamine ELISA for oral fluid. Substantial equivalence has been demonstrated through performance testing to verify that the device functions as intended and that design specifications have been satisfied.

{5}------------------------------------------------

Image /page/5/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its body and wings. The logo is surrounded by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement. The text is in all capital letters and is evenly spaced around the circular border.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Microgenics Corporation c/o Lisa Charter Manager, Regulatory Affairs 46360 Fremont Blvd. Fremont, CA 94538

APR 0 8 2011

Re: K101745

Trade Name: Thermo Scientific CEDIA Amphetamine OFT Assay Regulation Number: 21 CFR §862.3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: DKZ 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).

{6}------------------------------------------------

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 tollfire mo (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

C.C.

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

{7}------------------------------------------------

Indications for Use

510(k) Number (if known): K101745

Device Name: Thermo Scientific CEDIA® Amphetamine OFT Assay

Indication for Use:

The CEDIA® Amphetamine OFT Assay is intended for use in the qualitative determination of amphetamine in human oral fluid at a cutoff concentration of 150 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-amphetamine and performed on the MGC 240. This in vitro diagnostic device is intended for clinical laboratory use only.

The CEDIA Amphetamine 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.

Prescription Use X (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)

Carol C. Benson

Division Sian-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K101745

Regulation Number and Section

§ 862.3100 Amphetamine test system.

(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine 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).