The DRI Amphetamines Assay is intended for the qualitative or semi-quantitative determination of amphetamine and methamphetamine in human urine. The assay has cutoff levels of 500 and 1000 ng/mL. The assay provides a simple and rapid analytical screening procedure for detecting amphetamine and methamphetamine in urine on automated clinical analyzers. The assay is calibrated with methamphetamine.

This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

Device Description

The DRI Amphetamines Assay is a liquid ready-to-use homogeneous enzyme immunoassay. The assay uses specific antibodies, which can detect amphetamine and/or methamphetamine in urine with minimal cross-reactivity to various over-the-counter structurally unrelated compounds. The assay is based on the competition of an enzyme glucose-6-phosphate dehydrogenase (G6PDH) labeled drug and the drug from the urine sample for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample, the specific antibody binds the drug labeled with G6PDH and causes a decrease in enzyme activity. In the presence of free drug, the free drug occupies the antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate, resulting in enzyme activity. This phenomenon creates a direct relationship between drug concentration in urine and the enzyme activity. The enzyme activity is determined spectrophotometrically at 340 nm by measuring its ability to convert nicotinamide adenine dinucleotide (NAD) to NADH.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Thermo Scientific DRI® Amphetamines Assay, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

Performance Metric	Acceptance Criteria (Design Input Specifications)	Reported Device Performance (Achieved)
Precision (Qualitative)	All negative samples recover as negative, all positive samples recover as positive.	All negative samples recovered as negative and all positive samples recovered as positive.
Precision (Semi-Quantitative)	Within-run %CV and total-run %CV meet design specifications.	Within run %CV for was less than or equal to 6.2% and the total run %CV was less than or equal to 6.9%. (The specific numerical design specifications for %CV are not explicitly stated, but the submission claims they were met.)
Accuracy / Method Comparison	Greater than 96% total agreement between the DRI methods and GC/MS for both qualitative and semi-quantitative assays.	Greater than 96% total agreement between the DRI methods and GC/MS for both qualitative and semi-quantitative assays. (Note: Discordant results were observed for individual analyte detection due to the assay's 100% cross-reactivity to both amphetamine and methamphetamine, but this was explained and seemingly accepted within the context of the overall agreement and intended use of a screening assay.)
Dilution Recovery (Linearity)	Recovery less than ±4% error of the expected value for levels tested throughout the assay range (0 to 2000 ng/ml).	Recovery was less than ±4% error of the expected value for levels tested from 0 to 2000 ng/ml. The assay dilutes in a linear fashion.
On-Board Open Vial Reagent Stability	Reagents stored on the analyzer are stable for a minimum of 60 days.	Reagents stored on the analyzer are stable for a minimum of 60 days.

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

Sample Size: The document does not provide specific numerical sample sizes for the precision, accuracy/method comparison, dilution recovery, or stability studies. It broadly states "Samples spiked with d-amphetamine and d-methamphetamine were tested" for precision, and "Samples were tested by DRI qualitative and semi-quantitative assay and compared to GC/MS" for method comparison.
Data Provenance: Not explicitly stated. Given it's a 510(k) submission for a diagnostic kit, the samples would likely be human urine samples, potentially spiked or clinical samples. It's common for such studies to be conducted internally or at contract research organizations in the country where the manufacturer is located (USA, in this case, Microgenics Corporation is in Fremont, CA). The study type appears to be prospective as it involves controlled testing to demonstrate performance.

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

Number of Experts: Not applicable in the context of this device.
Qualifications of Experts: Not applicable. For drug screening assays, the "ground truth" is typically established by a highly specific and sensitive reference method.

4. Adjudication Method for the Test Set:

Adjudication Method: Not applicable. The ground truth is established by a reference analytical method (GC/MS) rather than human adjudication of interpretations.

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

MRMC Study: No, this type of study was not performed. MRMC studies are typically for image-based diagnostic devices where multiple human readers interpret cases. This device is an in-vitro diagnostic assay.
Effect Size of Human Readers with/without AI Assistance: Not applicable.

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

Standalone Study: Yes, the performance studies described (Precision, Accuracy/Method Comparison, Dilution Recovery, Stability) represent the standalone performance of the device/assay without human interpretation beyond standard laboratory procedures (e.g., loading samples, reading results from an automated analyzer). The assay itself is an "algorithm" in the chemical sense, providing a result.

7. The Type of Ground Truth Used:

Type of Ground Truth: The primary ground truth used for method comparison (accuracy) was Gas Chromatography/Mass Spectrometry (GC/MS). GC/MS is widely considered the gold standard for confirming the presence and concentration of drugs in urine samples due to its high specificity and sensitivity. For precision, the "ground truth" was derived from the known concentrations of spiked samples.

8. The Sample Size for the Training Set:

Sample Size for Training Set: The document does not specify a separate "training set" or its size. For an in-vitro diagnostic assay like the DRI Amphetamines Assay, the development process might involve numerous experiments and optimization steps that could be considered analogous to "training." However, the 510(k) summary focuses on the final validation/test set. The assay itself is based on a chemical reaction and antibody-antigen binding kinetics, not a machine learning algorithm that requires a distinct training dataset in the same way.

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

Ground Truth for Training Set: Not explicitly stated as a distinct "training set" in the context of machine learning. The "ground truth" during the development and optimization of such an assay would involve known concentrations of amphetamines and methamphetamines in urine, validated through highly accurate analytical methods, to ensure the assay's reagents, reaction conditions, and calibration curve are optimized to accurately detect and quantify the target analytes. This iterative process is part of the assay's design and engineering.

Summary

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510(k) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of Safe Medical Devices Act of 1990 and 21 CFR 807.92

The assigned 510(k) number is: K093114

COMPANY/CONTACT PERSON

Hewuan Takkele Regulatory Affairs Specialist Microgenics Corporation Thermo Fisher Scientific, Clinical Diagnostics Division 46360 Fremont Blvd. Fremont, CA 94538 (510) 979-5000 x31860 Office (510) 979-5422 Fax Hewuan.Takkele@thermofisher.com

DATE PREPARED

May 10, 2010

DEVICE NAME

Trade Name:	Thermo Scientific DRI® Amphetamines Assay
Common Name:	DRI® Amphetamines Assay
Device Classification:	Amphetamine test system, Methamphetamine Test System
Regulation number:	21 CFR 862.3100, 21 CFR 862.3610
Product Code:	DKZ, LAF

INTENDED USE

SUBSTANTIALLY EQUIVILANT PREDICATE DEVICE

Thermo Scientific DR1° Amphetamines Assay is substantially equivalent to the previously cleared CEDIA® DAU Amphetamines Assay (K943993).

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SUMMARY AND EXPLANATION OF THE TEST

Amphetamines are synthetic derivatives of ephedrine. The most common amphetamines include d-amphetamine, d-methamphetamine, and d, I-amphetamine. They act as stimulants for the central nervous system. Amphetamine is the most sympathomimetic amine. When amphetamine is ingested, it is either

rapidly deactivated in the liver or excreted unchanged into the urine. Other ephedrine derivatives such as methamphetamine can be metabolized and excreted in urine as amphetamine.

Comparison	CEDIA® Amphetamines Assay (K943993)	Thermo ScientificDRI® Amphetamines Assay (K093114)
IntendedUse	The CEDIA® Amphetamines assay is an in-vitrodiagnostic medical device intended for the qualitativeand semi quantitative assay of amphetamines inhuman urine.The assay provides only a preliminary analytical testresult. A more specific alternative chemical methodmust be used to obtain a confirmed analytical result.Gas chromatography/mass spectrometry (GC/MS) isthe preferred confirmatory method.1 Clinicalconsideration and professional judgment should beapplied to any drug of abuse test result particularlywhen preliminary positive results are used.	The DRI Amphetamines Assay is intended for thequalitative or semi-quantitative determination ofamphetamine and methamphetamine in humanurine. The assay has cutoff levels of 500 and 1000ng/mL. The assay provides a simple and rapidanalytical screening procedure for detectingamphetamine and methamphetamine in urine onautomated clinical analyzers. The assay iscalibrated with methamphetamine.This assay provides only a preliminary analyticaltest result. A more specific alternative chemicalmethod must be used in order to obtain aconfirmed analytical result. Gaschromatography/mass spectrometry (GC/MS) is thepreferred confirmatory method. Clinicalconsideration and professional judgment should beapplied to any drug of abuse test result, particularlywhen preliminary positive results are used.
TestPrinciple	The CEDIA Amphetamines assay uses recombinantDNA technology (US Patent No. 4708929)to produce a unique homogeneous enzymeimmunoassay system.7 This assay is based onthe bacterial enzyme β-galactosidase, which hasbeen genetically engineered into two inactivefragments. These fragments spontaneouslyreassociate to form fully active enzyme that, in theassay format, cleaves a substrate, generating a colorchange that can be measured spectrophotometrically.In the assay, drug in the sample competes with drugconjugated to one inactive fragment of	The DRI Amphetamines Assay is a liquid ready-to-use homogeneous enzyme immunoassay. Theassay uses specific antibodies, which can detectamphetamine and/or methamphetamine in urinewith minimal cross-reactivity to various over-the-counter structurally unrelated compounds. Theassay is based on the competition of an enzymeglucose-6-phosphate dehydrogenase (G6PDH)labeled drug and the drug from the urine sample fora fixed amount of specific antibody binding sites. Inthe absence of free drug from the sample, thespecific antibody binds the drug labeled with

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

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	ß-galactosidase for antibody binding site. If drug ispresent in the sample, it binds to antibody,leaving the inactive enzyme fragments free to formactive enzyme. If drug is not present inthe sample, antibody binds to drug conjugated on theinactive fragment, inhibiting the reassociation ofinactive ß-galactosidase fragments, and no activeenzyme will be formed.The amount of active enzyme formed and resultantabsorbance change are proportional tothe amount of drug present in the sample.	G6PDH and causes a decrease in enzyme activity.In the presence of free drug, the free drug occupiesthe antibody binding sites, allowing the drug-labeled G6PDH to interact with the substrate,resulting in enzyme activity. This phenomenoncreates a direct relationship between drugconcentration in urine and the enzyme activity. Theenzyme activity is determinedspectrophotometrically at 340 nm by measuring itsability to convert nicotinamide adenine dinucleotide(NAD) to NADH.
Cutoff	500 and 1000 ng/mL	500 and 1000 ng/mL
Matrix	Human Urine	Human Urine
Reagents	Lyophilized	Liquid Ready-to-Use
	Two reagent assay (R1 and R2)	Two reagent assay (R1 and R2)
Calibrators	Liquid ready-to-use	Liquid ready-to-use
	(0, 500, 1000, 3000, 5000 ng/mL)	(0, 500, 1000, 1500, 2000 ng/mL)
Controls	Liquid ready-to-use	Liquid ready-to-use
	(375 and 625, 750 and 1250 ng/mL)	(375 and 625, 750 and 1250 ng/mL)
StorageCondition	2-8°C	2-8°C

PERFORMANCE TESTING SUMMARY

Precision and Accuracy

Samples spiked with d-amphetamine and d-methamphetamine were tested for precision in qualitative and semi-quantitative assays following a randomized CLSI protocol. The precision study met the design specifications in both the qualitative and semi-quantitative assays. In the qualitative study, all negative samples recovered as negative and all positive samples recovered as positive. In the semi-quantitative study, the within run %CV for was less than or equal to 6.2% and the total run %CV was less than or equal to 6.9%.

Method Comparison

Samples were tested by DRI qualitative and semi-quantitative assay and compared to GC/MS. The method comparison exhibited results greater than 96% total agreement between the DRI methods and GC/MS for both qualitative and semi-quantitative assays. Discordant results were obtained when the assay was used to detect amphetamine and methamphetamine analytes individually. The assay detects the presence of both amphetamine and methamphetamine analytes with 100% cross reactivity to both drugs. Therefore samples tested for one analyte may appear discordant due to the presence of the other analyte.

The method comparison results meet the design input specifications.

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Dilution Recovery

Samples were tested to demonstrate linearity throughout the assay range. Results showed that recovery was less than ±4% error of the expected value for levels tested from 0 to 2000 ng/ml.. The results met the design input specification for levels tested throughout the assay range, and the assay dilutes in a linear fashion.

On-Board Open Vial reagent Stability

Uncapped reagents were stored in an analyzer and all calibrators and controls were tested in qualitative and semi-quantitative assay. Reagents stored on the analyzer are stable for a minimum of 60 days.

CONCLUSION

As summarized, the Thermo Scientific DRI® Amphetamines Assay is substantially equivalent to the CEDIA® Amphetamines Assay. 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/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" is arranged in a circular fashion around the bird-like figure.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Microgenics, Inc. C/O Hewuan Takkele 46360 Fremont Blvd. Fremont, CA 94538

Re: K093114

Trade/Device Name: DRI Amphetamines Assay Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: DKZ, LAF Dated: May 7, 2010 Received: May 10, 2010

MAY 1 2 2010

Dear Ms. Takkele:

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 class II (Special Controls), 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). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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 postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Signature

Courtney C. 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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Indication for Use

510(k) Number (if known): K093114

Device Name: DRI® Amphetamines Assay

Indication for Use:

This assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used in order to obtain a con firmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. 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)

Division State Officer

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

510(k) K093114

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).