The CEDIA® Opiate OFT Assay is intended for use in the qualitative determination of opiate in human oral fluid at a cutoff concentration of 30 ng/mL in neat oral fluid. The specimen must be collected exclusively with the Oral-Eze™ Saliva Collection System. The assay is calibrated against morphine and performed on the MGC240. This in vitro diagnostic device is intended for clinical laboratory use only.

The CEDIA Opiate 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.

Device Description

Microgenics CEDIA® Opiate 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. These fragments spontaneously re-associate to form fully active enzyme that, in the assay format, cleave 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 (enzyme donor) of β-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragment free to form active enzyme. If the analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the re-association of inactive β-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 analyte 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.

AI/ML Overview

This document describes the acceptance criteria and the study performance for the CEDIA® Opiate OFT Assay, a device intended for the qualitative determination of opiates in human oral fluid.

1. Table of Acceptance Criteria and Reported Device Performance

Parameter	Acceptance Criteria (Implied)	Reported Device Performance
Qualitative Precision	Samples below cutoff read negative; samples above cutoff read positive. Accurately recover results.	All samples tested recovered accurately. Samples below cutoff read as negative, and samples above cutoff read as positive.
Qualitative Cutoff Characterization	Low control read negative; high control read positive. Accurately recover results.	All samples tested recovered accurately. Low control as negative and high control level as positive.
Interference	No significant interference from endogenous and exogenous substances.	No significant interference from endogenous and exogenous substances at specified concentrations and pH.
Specificity/Cross-Reactivity	No significant cross-reactivity with structurally unrelated compounds.	No significant cross-reactivity observed with structurally unrelated compounds.
Overall Concordance (vs. GC/MS)	High overall concordance with GC/MS (specific threshold not explicitly stated but implied by "substantial equivalence").	97.6% overall concordance between CEDIA® Opiate OFT Assay and GC/MS.
Sensitivity (vs. GC/MS)	High sensitivity (specific threshold not explicitly stated).	100.0% sensitivity.
Specificity (vs. GC/MS)	High specificity (specific threshold not explicitly stated).	95.2% specificity.

Note: The document implies acceptance criteria based on the reported "accurate" recovery and "no significant" interference/cross-reactivity, along with high concordance/sensitivity/specificity values.

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

The document does not explicitly state the exact sample size for the "test set" used in the method comparison study. It only mentions "The overall concordance between the CEDIA® Opiate OFT Assay and GC/MS is 97.6%."

Data Provenance: The document does not specify the country of origin of the data. It is a retrospective study comparing the new assay's results against a confirmatory method (GC/MS).

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

This device is an in vitro diagnostic (IVD) assay, not an imaging or interpretation device that typically relies on human experts for ground truth establishment in the same way clinical diagnostic studies might.

For IVD assays like this, the "ground truth" for the test set is established by a confirmatory analytical method, in this case, Gas Chromatography/Mass Spectrometry (GC/MS). Therefore, the concept of "number of experts" and their "qualifications" for establishing ground truth as it would apply to interpretive tasks (e.g., radiologists reading images) is not directly applicable here. The experts involved would be the laboratory personnel performing and interpreting the GC/MS results, who are qualified to operate and interpret results from such sophisticated analytical equipment.

4. Adjudication Method for the Test Set

Not applicable. As described above, the ground truth is established by a confirmatory analytical method (GC/MS), not by human expert consensus or adjudication in the traditional sense. Discordant results between the CEDIA® Opiate OFT Assay and GC/MS would be resolved by the GC/MS result, which is considered the "gold standard" for confirmation.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This is an in vitro diagnostic assay, and its performance is evaluated based on its analytical characteristics and concordance with a reference method, not human reader performance.

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

Yes, a standalone performance evaluation was done. The study assesses the performance of the CEDIA® Opiate OFT Assay itself, comparing its results directly to the GC/MS confirmatory method without human interpretation as an intermediate step. The assay provides a "preliminary analytical test result" which then requires confirmation by GC/MS or LC-MS/MS.

7. The Type of Ground Truth Used

The type of ground truth used is confirmatory analytical testing, specifically Gas Chromatography/Mass Spectrometry (GC/MS). The document states: "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."

8. The Sample Size for the Training Set

The document does not provide information about a "training set" or "training data" in the conventional sense used for machine learning algorithms. This is an immunoassay, and its development involves analytical validation, not a distinct training phase with a labeled dataset in the way AI/ML devices do. The performance characteristics are established through various analytical studies (precision, cutoff characterization, interference, specificity, method comparison).

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

Not applicable. As mentioned above, this is an immunoassay and does not have a "training set" in the context of machine learning. The assay mechanism is based on biochemical reactions and genetic engineering (recombinant DNA technology), not on learning from a dataset.

Summary

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APR - 8 2011

510K SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in summary of STO(K) salety and enectronics of SMDA 1990 and 21 CFR 807.92

The assigned 510(k) number is: K101754

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

January 6, 2011

Requiatory Declarations

Common / Usual Name	CEDIA® Opiate OFT Assay
Trade/ Proprietary Name	Thermo Scientific CEDIA® Opiate OFT Assay
Classification Regulation	21 CFR 862.3650
Device Class	Class II
Device Regulation Panel	Toxicology
Product Code	DJG

Intended use

The CEDIA® Opiate OFT Assay is intended for use in the qualitative determination of The CEDIA "Oplate Of T Assay is Intended for 30 ng/mL in neat oral fluid. The oplate in numan oral liud at a caton contonitution of 50 mg Saliva Collection System. The specimen must be collected exclusively with the era on the MGC240. This in vitro assay is oulibrator againical laboratory use only.

The CEDIA Opiate OFT Assay provides only a preliminary analytical test result. A more The CEDIA Oplate OF TASSY provides only and to obtain a confirmed analytical result. Gas specific alternative method must be used (b Chromatography-Tandem Mass
Chromatography/Mass Spectrometry (GC/MS) and Liquid Chromatography-Tandemical in ChromalographyMass Spectrometry (GOATS) and internations . Olinical consideration Spectrometly (CC-MS/NG) are the profess somments) of abuse test result particularly when preliminary positive results are used.

Conditions for use

The CEDIA® Opiate OFT Assay is for prescription professional use only in clinical The - OEDIA - Oplate - It is not for use in Point of Care settings.

Legally marketed device to which equivalency is claimed

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CEDIA® Opiate OFT Assay is substantially equivalent to the previously cleared STC Opiates MICRO-PLATE EIA, K981341 (At present OTI, OraSure Technologies Inc.)

DESCRIPTION OF DEVICE

Principle of the CEDIA® Opiate OFT Assay

In the assay, analyte in the sample competes with analyte conjugated to one inactive fragment (enzyme donor) of β-galactosidase for antibody binding site. If analyte is praesent in the sample, it binds to antibody, leaving the inactive enzyment free to form active enzyme. If the analyte is not present in the sample, antibody binds to analyte conijugated on the inactive fragment, inhibiting the re-association of inactive B-galectosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and fightently, absorbance change are directly proportional to the amount of analyte present it 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 adecruacy 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® Opiate OFT Assay is substantially equivalent to the OTI Opiates MICRO-PLATE EIA. (K981341)

Comparison	Subject DeviceCEDIA® Opiate OFT Assay	Predicate DeviceOTI Opiates MICRO-PLATE EIAK981341
Intended Use	The CEDIA® Opiate OFT Assay isintended for use in the qualitativedetermination of opiate in humanoral fluid at a cutoff concentration of30 ng/mL in neat oral fluid. Thespecimen must be collectedexclusively with the Oral-Eze™Saliva Collection System. The assayis calibrated against morphine andperformed on the MGC240. This invitro diagnostic device is intendedfor clinical laboratory use only.The CEDIA Opiate OFT Assayprovides 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 OTI Opiates MICRO-PLATEEIA is intended for use in thequalitative determination of opiatesin oral fluid collected with theOraSure® Oral Collection Device.For In Vitro Diagnostic Use.
TestPrinciple	Microgenics CEDIA® Opiate OFTAssay uses recombinant DNAtechnology to produce a uniqueenzymehomogeneousimmunoassay system. The assay isbased on the bacterial enzyme ß-galactosidase, which has beengenetically engineered into twoinactive fragments. These fragmentsspontaneously re-associate to formfully active enzyme that, in theassay format, cleave a substrate,generating a color change that canbe measuredspectrophotometrically.In the assay, analyte in the sample	The OTI Opiates is a competitivemicro-plate immunoassay for thedetection of opiates in oral fluidcollected with the OraSure® OralSpecimen Collection Device.Specimen or standard is added toan EIA well in combination with anenzyme-labeled hapten derivative.In an EIA well containing anOraSure® specimen positive foropiates, there is a competitionbetween the drug and the enzyme-labeled hapten to bind the antibodyfixed onto the EIA well. ElA wellsare then washed, substrate isadded, and color is produced. Theabsorbance measured for each wellat 450nm is inversely proportional to
one inactive fragment (enzyme donor) of β-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragment free to form active enzyme. If the analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the re-association of inactive β-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 analyte present in the sample.	the amount of opiates present in the specimen or calibrator/control.
SampleMatrix	Oral Fluid	Oral Fluid
Calibratorlevels .	0, 10.0, 80.0 ng/mL	0, 10 ng/mL
Cutoff level	30.0 ng/mL in neat oral fluid	10.0 ng/mL
UnassayedControllevels	5.0, 15.0 ng/mL	5.0, 20.0 ng/mL

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. . . . . .

and the contraction of the comments of the comments of the comments of

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SUMMARY OF CLINICAL TESTING

Qualitative Precision

All samples tested recovered accurately. Samples at levels below the cutoff read as negative All samples tested recoverou assembly
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.

Interferences

Results demonstrated that there was no significant interference from endogenous and Results demonstrated that there was The Sighlindine interested oncentrations 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 Cross-reactivity to metabolites and Structurally related of the structurally unrelated compounds.
significant cross-reactivity was observed with other structurally unrelated

Method Comparison

The overall concordance between the CEDIA® Opiate OFT Assay and GC/MS is 97.6%. The over 100.0 % The overall concordance between the CEDIA "Opiate OFT Assay to GCMS showed 100.0 %
comparison of sample results by the CEDIA® Opiate OFT Assay to GCMS showed 100.0 % sensitivity and 95.2 % specificity.

Conclusion

As summarized, the CEDIA® Opiate OFT Assay is substantially equivalent to the OTI Opiates As summarized, the CEDIA Opliale Of 1 Assay Jobsentation through performance
MICRO-PLATE EIA. Substantial equivalence has been demonstrations have been MICRO-PLATE EIA. Substantial equivalence Nas boom democracy in 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 and Human Services. The logo consists of a stylized eagle with its wings spread, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular pattern around the eagle. The eagle is depicted in a simple, black and white design.

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

Microgenies Corp. ThermoFisher Scientific, Clinical Diagnostic Division c/o Ms. Lisa Charter Manager, Regulatory Affairs 46360 Fremont Blvd. Fremont, CA 94538-6406

APR 0 8 2011

Re: K101754

Trade Name: Thermo Scientific CEDIA Opiate OFT Assay Regulation Number: 21 CFR §862.3650 Regulation Name: Opiate test system Regulatory Class: Class II Product Codes: DJG 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-free number (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): K101754

Device Name: CEDIA® Opiate OFT Assay

Indications for Use:

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 Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) k/01754

Regulation Number and Section

§ 862.3650 Opiate test system.

(a)
Identification. An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.(b)
Classification. Class II (special controls). An opiate 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).