The UPlink™ Oral Fluid Drug Test is a rapid immunoassay intended for use with the UPlink™ Analyzer for the qualitative detection of opiates in oral fluid using a 40 ng/mL cutoff. FOR IN VITRO DIAGNOSTIC USE.

The UPlink™ Test System provides only a preliminary analytical test result. A more specific alternate 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 drugs of abuse test result, particularly when a preliminary, positive result is observed.

Device Description

UPlinkTM is the trademark name for a new, rapid, onsite testing technology. The basis for the test is Up-Converting Phosphor Technology (UPT). UPT particles are small nanospheres composed of rare earth metals that are labeled with antibodies against targeted drugs of abuse. Similar particles have been used for decades in display screens such as televisions or fluorescent light bulbs. Different from the particles used in televisions, UPT particles are excited by infrared light and up-convert the energy to give a visible emission. This is an anti-stokes shift that does not exist in nature. In addition, just like current display screens, UPT particles are available in different colors to allow multiplexing and do not fade or photobleach.

The UPlink™ Test, in conjunction with the UPlink™ Analyzer and oral fluid collection device, is a lateral flow, panel immunoassay for the rapid qualitative measurement of opiates in oral fluid. The UPlinkTM collection device gathers the oral fluid sample for analysis from the mouth and into a test cassette, The UPlink™ Analyzer measures the intensity of the signal line(s) on the cassette and converts it to a qualitative result(s).

The test consists of a protective cassette housing containing a lateral flow strip of plastisbacked nitrocellulose that has been impregnated with test and reference lines. Phosphor particles conjugated with analyte-specific antibodies are dried into a pad adjoined to the nitrocellulose strip and in physical contact with both the strip and an overlying absorbent pad. With addition of the oral fluid sample to the cassette, the phosphor-antibody complexes move with the sample by capillary action to contact the test line. When opiates are present in the oral fluid sample, the drug with the phosphorantibody conjugate during flow and the phosphor-antibody-drug complexes will not bind further to the analyte derivative on the test line. As a result, subsequent excitation of the URink™ Analyzer will not produce a signal. If no drug is present in the sample, phosphor-antibody complexes will bind to the test line, giving a high signal strength at the test line is inversely proportional to the amount of opiates present in the sample. The assay reference band is not influenced by the presence or absence of drug in the oral fluid, and therefore, will be present in all reactions.

The UP oral fluid collection device consists of a cellulose sponge donut contained in aplastic housing with a removable handle. The collector is used to continuously swab the mouth between the cheek and gum for 1 to 2 minutes. As sample is collected, the cellulose sponge expands, ensuring that an adequate amount of sample is obtained in each collection. The collection device is inserted into the an accquate and pushed down to crack a small ampoule of buffer, followed by removal of the handle so the test cassette can be inserted into the UPIinkTM Analyzer.

The UPIink™ Analyzer is a portable instrument containing a laser source that interrogates the test strip for signals produced by the test and reference lines. Detection of a signal for the reference line indicates the validity of the test. The intensity of the signal for the test line is indirectly proportional to the concentration of the analyte. The test strip's lot specific calibration curve is contained in a barcode on each cassette. By its use the instrument converts the measured signal into a positive or negative result that is displayed to the user.

AI/ML Overview

The UPlink™ Test System is a rapid immunoassay for the qualitative detection of opiates in oral fluid using a 40 ng/mL cutoff, intended for in vitro diagnostic use. It provides a preliminary analytical test result, with Gas chromatography/mass spectrometry (GC/MS) being the preferred confirmatory method.

Here's an analysis of its acceptance criteria and the supporting study:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA 510(k) summary only explicitly states the acceptance criteria for the predicate device, which is 90% agreement as compared to GC/MS. The performance of the UPlink™ Test System is then compared to this benchmark.

Criterion Type	Acceptance Criteria (Predicate)	Reported Device Performance (UPlink™ Test System)
Clinical Accuracy	90% agreement as compared to GC/MS	Data presented below (detailed breakdown)
Precision	Not explicitly stated for UPlink™ comparison	97-100% agreement when drug levels were tested at +/- 25% and 50% of the cutoff
		3.6-6.9% CV (Intra-assay)
		7.5-9.5% CV (Inter-assay)
Limit of Detection	Not explicitly stated for UPlink™ comparison	30 ng/mL

Detailed Clinical Accuracy Performance for UPlink™ Test System (compared to GC/MS/MS):

Study 1: Poppy Seed Ingestion
- Agreement: 100% (30/30 individuals rendered a positive result by Uplink and were confirmed positive by GC/MS/MS).
- GC/MS/MS Range: 72-440 ng/mL codeine and 560-2640 ng/mL morphine.
Study 2: Codeine Ingestion (16 mg)
- GC/MS/MS Combined Morphine & Codeine (ng/mL) | Uplink Negative | Uplink Positive |
  |---------------------------------------------------|---------------------|---------------------|
  | 16.9-38.8 | 8 | 5 |
  | 40-56 | 8 | 3 |
  | > 60 | 6 | 8 |
Study 3: Non-drug users and Drug Rehabilitation/Treatment Centers
- GC/MS/MS Combined Morphine & Codeine (ng/mL) | Uplink Negative | Uplink Positive |
  |---------------------------------------------------|---------------------|---------------------|
  | None detected* | 119 | 22 |
  | 3.6-28** | 7 | 1 |
  | 8.4-60*** | 2 | 4 |
  | >72*** | 2 | 13 |
- * Almost all samples were evaluated for the presence of 6-mam; none was found.
- ** All samples were evaluated for the presence of 6-mam; none was found.
- *** Almost all samples were evaluated for the presence of 6-mam; all samples but one contained > 4.4 ng/mL of 6-mam.

2. Sample Sizes and Data Provenance

Test Set Sample Size: A total of 238 oral fluid samples across three separate studies.
- Study 1: 30 individuals
- Study 2: Number of individuals not explicitly stated, but results are presented across concentration ranges.
- Study 3: 170 samples
Data Provenance: Not explicitly stated regarding country of origin. The studies involve "individuals who ingested poppy seed filling," "individuals ingested 16 mgs of codeine," and "a mixture of non-drug users and individuals enrolled in drug rehabilitation or drug treatment centers." This suggests prospective collection for the first two studies, and a mix of prospective and potentially retrospective (for drug treatment center patients) for the third study. All data appears to be clinical in nature.

3. Number of Experts and their Qualifications for Ground Truth

The ground truth was established by Gas chromatography/mass spectrometry (GC/MS or GC/MS/MS), which is a laboratory analytical method, not human expert interpretation in this context. Therefore, the concept of "number of experts" and their "qualifications" for establishing this specific ground truth is not applicable. The GC/MS/MS results are considered the objective gold standard for drug detection and quantification.
- The document implies that laboratory personnel are qualified to perform and interpret GC/MS/MS results, but no specific number or qualifications are given.

4. Adjudication Method for the Test Set

No human adjudication method is described for the test set. The UPlink™ Test System results were directly compared against the objective GC/MS/MS results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No mention of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study. This device is an automated, objective test system, not an imaging or diagnostic tool requiring human interpretation that could be "improved with AI assistance." It produces a qualitative (positive/negative) result via an attached analyzer.

6. Standalone Performance

Yes, the performance data presented is for the standalone (algorithm only without human-in-the-loop performance) of the UPlink™ Test System. The UPlink™ Analyzer reads the test strip and converts the measured signal into a positive or negative result, which is then compared to GC/MS/MS. There is no human interpretation involved in the device's output.

7. Type of Ground Truth Used

The type of ground truth used is laboratory analytical gold standard: Gas chromatography/mass spectrometry (GC/MS or GC/MS/MS). This method is the "preferred confirmatory method" and is used as the basis for comparison for the UPlink™ Test System.

8. Sample Size for the Training Set

The document does not provide any information regarding a distinct "training set" for the UPlink™ Test System. The system's "lot specific calibration curve is contained in a barcode on each cassette," implying that the device is calibrated, but the data used for establishing this calibration or any model training is not disclosed in this summary. This is typical for a premarket notification for an in vitro diagnostic device from this era, where traditional analytical validation rather than machine learning model validation was the norm.

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

As no training set is explicitly mentioned or detailed, there is no information on how its ground truth would have been established. For devices relying on calibration curves, the ground truth for calibration would involve known concentrations of analytes (opiates) measured by a reference method (likely GC/MS/MS) during the manufacturing or development process.

Summary

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K020371

APR 0 3 2002

PREMARKET NOTIFICATION 510(k) SUMMARY (As Required By 21 CFR 807.92)

807.92 (a):

Submitter's Name:	OraSure Technologies, Inc. (OTI)
Address:	150 Webster St., Bethlehem, PA 1801
Telephone Number:	(610) 882-1820
Contact Person:	R. Sam Niedbala, Ph.D., BCFE
Date Prepared:	January 31, 2002

1. Device Name: UPlinkTM Test System Proprietary Name: UPlink™ Test System Usual Name: Enzyme immunoassay, opiates Classification Name:
Device to Which Substantial Equivalence Is Claimed: 3. Opiates Intercept™ MICRO-PLATE EIA; K981341
1. Description of Device:

UPlinkTM Platform Overview

The UP oral fluid collection device consists of a cellulose sponge donut contained in aplastic housing with a removable handle. The collector is used to continuously swab the mouth between the

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cheek and gum for 1 to 2 minutes. As sample is collected, the cellulose sponge expands, ensuring that an adequate amount of sample is obtained in each collection. The collection device is inserted into the an accquate and pushed down to crack a small ampoule of buffer, followed by removal of the handle so the test cassette can be inserted into the UPIinkTM Analyzer.

રું Intended Use Statement:

uptpresm

The UPlink™ Oral Fluid Drug Test is a rapid immunoassay intended for use with the UP/ink™ Analyzer for the qualitative detection of opiates in oral fluid using a 40 ng/mL cutoff. FOR IN VITRO DIAGNOSTIC USE.

a. Summary of Technological Characteristics: 6.

The OTI UPlink™ Test System is based on the principle of solid phase competitive immunoassay in a lateral flow format. This application is for the use of the UPlink™ Oral Fluid Drug Test as a screening tool for the detection of opiates in oral fluid collected with the UPlink™ oral fluid collection device (provided with the test cassette) and analyzed with the UPlink™ Analyzer.

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b. Summary of Performance Data:

b. Summary of Performance Data:
The performance characteristics of the OTI UPlink™ Test System is suivalent to the legally The performance characteristics of this device is essentially equivalent to the legally marketed predicate device.

Proposed:						Predicate:
UPlink™ Test System						Intercept™ MICRO-PLATE EIAS
Performance Characteristics:						90% agreement ascompared to GC/MS
Clinical Accuracy:	- A total of 238 oral fluid samples were collected in three separatestudies.The first study involved individuals who ingested 1 teaspoon ofpoppy seed filling. Samples were collected within 10 minutes afteringestion. All 30 individuals rendered a positive result by the Uplinksystem and samples were found to contain between 72-440 ng/mL ofcodeine and between 560-2640 ng/mL morphine by GC/MS/MS.In the second study, individuals ingested 16 mgs of codeine.Samples were collected for several hours after ingestion. Uplinkresults are compared to GC/MS/MS results (morphine and codeineadded together):
		16.9-38.8ng/mL	40-56mg/mL	> 60mg/mL
	Uplink Negative	8	8	6
	Uplink Positive	5	3	8
	The third study involved the collection and testing of 170 samplesfrom a mixture of non-drug users and individuals enrolled in drugrehabilitation or drug treatment centers. Uplink results are comparedto the GC/MS/MS results (morphine and codeine added together).
		None detected*	3.6-28mg/mL**	8.4-60 ng/mL***	>72ng/mL***
	Uplink Negative	119	7	2	2
	Uplink Positive	22	1	4	13
	* Almost all samples were evaluated for the presence of 6-mam.None was found. All samples were evaluated for the presence of 6-mam. None wasfound.* Almost all samples were evaluated for the presence of 6-mam.All samples but one contained greater than 4.4 ng/mL of 6-mam.

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Precision:	97-100% agreement when drug levels were tested at +/- 25% and 50% of the cutoff	3.6-6.9% (Intra-assay) Based upon optical density units as %CV	7.5-9.5% (Inter-assay)
Limit of Detection:	30 ng/mL	1.4 ng/mL

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or a stylized human figure with outstretched arms. The symbol is composed of three curved lines that converge at the bottom.

Public Health Service

ood and Drug Administrat 2098 Gaither Road Rockville MD 20850

R. Sam Niedbala, Ph.D., BCFE Chief Science Officer OraSure Technologies, Inc. 1745 Eaton Avenue Bethlehem, PA 18015-1389

APR 0 3 2002

K020371 Re:

Trade/Device Name: UPlink™ Test System Regulation Number: 21 CFR 862.3650; 21 CFR 862.3280; 21 CFR 862.2150 Regulation Name: Opiate test system; Clinical toxicology control material; Continuous flow sequential multiple chemistry analyzer for clinical use Regulatory Class: Class II; Class II; Class II Product Code: DJG; DIF; JJC

Dated: January 31, 2002 Received: February 4, 2002

Dear Dr. Niedbala:

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 the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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STATEMENT OF INDICATIONS FOR USE

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: UPlink™ Test System

Indications For Use:

The UPlink™ Test System provides only a preliminary analytical test result. A more specific alternate 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 a preliminary, positive result is observed.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Ruth chule for. Jom Cooper

(Division Sign-Off) Division of Clinical Laboratory Devices 020 510(k) Number.

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

c:\fda\indica.doc

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).