The AMPH Flex® reagent cartridge used on the Dimension clinical chemistry system provides reagents for an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of amphetamines in human urine using a cutoff of either 300, 500 or 1000ng/mL. Measurements obtained with the AMPH method are used in the diagnosis and treatment of amphetamines use or overdose.

The AMPH method 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. Other chemical confirmation methods are available. 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 Dade Behring Dimension® AMPH method is an in vitro diagnostic device that consists of prepackaged reagents in a plastic cartridge (Flex®) for use on the Dade Behring Dimension® clinical chemistry system.

AI/ML Overview

The provided document does not explicitly state acceptance criteria in a quantitative format as commonly seen for medical device performance. Instead, it presents performance data by comparing the Dimension® Urine Amphetamines/Methamphetamine Screen Flex® (AMPH Flex®) reagent cartridge against a predicate device (Syva® Emit® II Plus Amphetamine Assay) and a reference method (GC/MS) at three different cutoffs (300, 500, and 1000 ng/mL). The "acceptance criteria" are implied by the agreement rates shown in the comparison tables.

Here's an analysis of the study based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

As explicit acceptance criteria (e.g., "must achieve >95% agreement") are not stated, the table below reflects the observed performance against the reference method (GC/MS). The implied acceptance is that the device demonstrates comparable or acceptable agreement with the gold standard (GC/MS).

Implied Acceptance Criteria and Reported Device Performance for AMPH Flex® Reagent Cartridge vs. GC/MS

Cutoff (ng/mL)	Performance Metric (Agreement with GC/MS)	Reported AMPH Flex® Performance	Interpretation of Acceptance
300	Positive Agreement (Sensitivity)	72/80 = 90%	Implied acceptance if sensitivity is deemed adequate for screening.
	Negative Agreement (Specificity)	49/49 = 100%	Implied acceptance if specificity is deemed adequate for screening.
	Discrepancy Analysis in ng/mL (Total cases: 129)	8 False Negatives (GC/MS Positive, AMPH Flex® Negative) at this cutoff.	Further analysis of false negatives would inform acceptance.
500	Positive Agreement (Sensitivity)	Data for "+" in AMPH Flex® vs. GC/MS is partially missing. The table for GC/MS comparison for cutoff 500 ng/mL does not explicitly show the total positives and negatives from GC/MS. The first row in the table is corrupted but seems to be a header. Manual counting of discrepant values suggests more data points are needed to complete this table.	Cannot calculate without complete table data.
	Negative Agreement (Specificity)	Data for "-" in AMPH Flex® vs. GC/MS is partially missing.	Cannot calculate without complete table data.
	Discrepancy Analysis in ng/mL (Total cases: 129)	14 False Negatives explicitly listed in the discrepant table.	Further analysis of false negatives would inform acceptance.
1000	Positive Agreement (Sensitivity)	Data for "+" in AMPH Flex® vs. GC/MS is partially missing. The table is corrupted.	Cannot calculate without complete table data.
	Negative Agreement (Specificity)	Data for "-" in AMPH Flex® vs. GC/MS is partially missing.	Cannot calculate without complete table data.
	Discrepancy Analysis in ng/mL (Total cases: 169)	14 False Negatives explicitly listed in the discrepant table.	Further analysis of false negatives would inform acceptance.

Note on missing data: The tables for cutoffs 500 ng/mL and 1000 ng/mL comparing AMPH Flex® to GC/MS are significantly corrupted in the provided text, making it impossible to fully populate the performance metrics. For example, for the 500 ng/mL cutoff against GC/MS there's a row 0 | | | | | Amer | A ARA (C (C) (C) (C) AN ANNUAL (C)<br>21 | and the same and the state of the states | | - | ----------------------------------------------------------------------------<br>8 !<br>. instead of proper counts. The 1000 ng/mL cutoff against GC/MS similarly has corrupted table data.

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

Sample Size:
- For 300 ng/mL cutoff: 129 native urine specimens
- For 500 ng/mL cutoff: 129 native urine specimens
- For 1000 ng/mL cutoff: 169 native urine specimens (with 129 having separate amphetamine and methamphetamine values suitable for SAMHSA confirmation guidelines)
Data Provenance: The data consists of "native urine specimens." No country of origin is specified. The study is retrospective, as it analyzes existing urine specimens.

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

The document does not explicitly state the number of experts or their qualifications for establishing the ground truth.
The ground truth was established by Gas Chromatography/Mass Spectrometry (GC/MS). While GC/MS is a laboratory method, expert interpretation of GC/MS results (e.g., "Positives by GC/MS were determined by using the criteria...") is implied. However, the document does not detail the personnel or their qualifications involved in this interpretation.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method involving human reviewers for discrepancies between the AMPH Flex® result and the GC/MS result. Discrepant values are simply listed with their GC/MS and AMPH Flex® (and sometimes predicate device) readings.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size of Human Improvement with AI vs. without AI Assistance

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic test, not an AI-assisted diagnostic tool for human readers. Therefore, the concept of human readers improving with or without AI assistance does not apply.

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

Yes, the performance study effectively represents a standalone performance. The AMPH Flex® reagent cartridge on the Dimension® clinical chemistry system is an automated in-vitro diagnostic device. Its performance is evaluated directly against the reference method (GC/MS) without human interpretation affecting the device's analytical result. The results ("Positives" or "Negatives" by AMPH Flex®) are direct outputs of the automated system.

7. The Type of Ground Truth Used

The ground truth used is Gas Chromatography/Mass Spectrometry (GC/MS), which is considered the preferred confirmatory method for amphetamines in urine. The criteria for defining a positive by GC/MS are explicitly stated for each cutoff level (e.g., "amphetamine plus methamphetamine > 300 ng/mL" for the 300 ng/mL cutoff). This can be classified as a definitive laboratory method (gold standard).

8. The Sample Size for the Training Set

The document does not provide any information regarding a training set or its sample size. This type of regulatory submission (510(k)) for a laboratory diagnostic test typically focuses on validation data to demonstrate substantial equivalence, rather than detailing the internal development and training of a machine learning algorithm.

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

As no information about a training set is provided, the method for establishing its ground truth is also not described.

Summary

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510(k) Summary for the Dimension® Urine Amphetamines/Methamethamine Screen Flex® (DF91B)

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.

510(k) Number: K040133

Analyte: Amphetamines/Methamethamine

Type of Test: qualitative or quantitative homogeneous enzyme immunoassay

A. Applicant: Dade Behring Inc.

Submitter's Name Andrea M. Tasker Building 500, Mailbox 514 P.O.Box 6101 Newark, DE 19714-6101
Submission Preparation Date January 20, 2004

B. Proprietary and Established Names: Dimension® Urine Amphetamines/Methamethamine Screen Flex® reagent cartridge

C. Regulatory Information:

1.Regulation section: 21CFR §862.3100 Amphetamine test system

1. Classification: Class II
1. Product Code: DKZ
1. Panel: Toxicology (91)

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D. Intended Use:

Indications for Use: The AMPH Flex® reagent cartridge used on the Dimension clinical chemistry system provides reagents for an in vitro diagnostic test intended for the qualitative and semi-quantitative determination of amphetamines in human urine using a cutoff of either 300, 500 or 1000ng/mL. Measurements obtained with the AMPH method are used in the diagnosis and treatment of amphetamines use or overdose.
Special conditions for use statements: The AMPH method 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. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

E. Device Description:

F. Substantial Equivalence Inforamtion:

1. Predicate Device: Syva® Emit® II Plus Amphetamine Assay
1. Predicate K Number(s): K031004
1. Comparision with Predicate: This product is substantially equivalent to other Amphetamine enzyme immunoassys, such as the Syva® Emit® II Plus Amphetamine Assay (K031004).

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I. Device Performance Characteristics: Method Comparison (cutoff=300 ng/mL)

129 native urine specimens were tested with the AMPH Flex® cartridge on the Dimension system (cutoff=300 ng/mL ) and with the Syva® Emit® II Plus Amphetamines Assay (9C309UL) on the Syva 30R Biochemical System (cutoff=300 ng/mL ). All 129 specimens were also analyzed by GC/MS. Positives by GC/MS were determined by using the criteria of amphetamine plus methamphetamine > 300 ng/mL since there are no SAMSHA confirmation guidelines for the 300 cutoff. 24 of these had total amphetamines by GC/MS within 25% of the 300 ng/mL cutoff.

Comparison to Predicate Method

Syva 30R® Biochemical System (cutoff 300 ng/mL)

AMPH Flex® Reagent Cartridge on the Dimension® clinical chemistry system (cutoff 300 ng/mL )

	+	-
+	70	2
-	2	55

Discrepants (ng/mL):

GC/MS	GC/MS	GC/MS	Dim	Syva
Meth	Amph	Total	AMPH	30R
242	61.1	303	315	273
433	<lod	433	325	298
275	70.2	345	278	300
363	<lod	363	204	301

< lod : less than the limit of detection, < 25 ng/mL

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Comparison to Reference Method

GCMS

(cutoff 300 ng/mL methamphetamine and amphetamine)

AMPH Flex®Reagent Cartridgeon Dimension®clinical chemistrysystem (cutoff 300ng/mL)	+	-
+	72	0
-	8	49

Discrepants (ng/mL):

GC/MS	GC/MS	GC/MS	Dim
Meth	Amph	Total	AMPH
253	47.2	300	95
311	< lod	311	240
326	< lod	326	189
313	< lod	313	240
363	< lod	363	204
255	67.3	322	271
275	70.2	345	278
279	71	350	296

< lod: less than the limit of detection of 25 ng/mL

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Method Comparison (cutoff=500 ng/mL )

129 native urine specimens were tested with the AMPH Flex® cartridge on the Dimension® system (cutoff=500 ng/mL ) and with the Syva® Emit® II Plus Amphetamines Assay (9C309UL) on the Syva 30R® Biochemical System (cutoff=500 ng/mL ). All 129 specimens were also analyzed by GC/MS. Positives by GC/MS were determined using the newly proposed SAMHSA guidelines by following the criteria of ≥ 250 ng/mL methamphetamine and ≥ 100 ng/mL amphetamine or > 250 ng/mL amphetamine regardless of the methamphetamine concentration. 28 of these had total amphetamines by GC/MS within 25% of the 500 ng/mL cutoff.

Comparison to Predicate Method

Syva 30R® Biochemical System (cutoff 500 ng/mL)

AMPH Flex® + Reagent Cartridge 43 0 on the Dimension® clinical chemistry system (cutoff 500 1 85 ng/mL )

Discrepants (ng/mL):

GC/MS	GC/MS	Dim	Syva
Meth	Amph	AMPH	30R
556	62.7	405	598

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Comparison to Reference Method

GCMS

(cutoff ≥ 250 ng/mL amphetamine

≥ 250 ng/mL metamphetamine and

≥ 100 ng/mL amphetamine)



Amer	A ARA (C (C) (C) (C) AN ANNUAL (C)21	and the same and the state of the states
	-	----------------------------------------------------------------------------8 !.

AMPH Flex® Reagent Cartridge on Dimension® clinical chemistry system (cutoff 500 ng/mL )

Discrepants (ng/mL):

GC/MS	GC/MS	Dim
Meth	Amph	AMPH
410	36.7	550
506	43.6	572
513	44.8	564
528	47.9	572
561	48.6	507
577	50.5	574
514	56.1	534
495	58.4	548
598	64.5	561
286	169	366
281	173	388
254	174	344
300	179	398
315	186	393

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Method Comparison (cutoff=1000 ng/mL )

169 native urine specimens were tested with the AMPH Flex® cartridge on the Dimension system (cutoff=1000 ng/mL ) and with the Syva® Emit® II Plus Amphetamines Assay (9C309UL) on the Syva 30R® Biochemical System (cutoff=500 ng/mL ). Total amphetamine and methamphetamine values by GC/MS were reported for these 169 specimens. Positives by Confirmation GC/MS were determined according to the SAMHSA requirements by following the criteria of > 500 ng/mL methamphetamine and ≥ 200 ng/mL amphetamine or ≥ 500 ng/mL amphetamine regardless of the methamphetamine concentration.

Separate amphetamine and methamphetamine values were available for only 129 of thes 169 specimens. Since separate amphetamine and methamphetamine values are required for confirmation testing according to the SAMSHA guidelines, only those 129 samples were represented in the box plot shown in Table 10. Of these 129, there were 9 which had total amphetamines by GC/MS within 25% of the 1000 ng/mL cutoff.

Comparison to Predicate Method

Syva 30R® Biochemical System (cutoff 1000 ng/mL)

	+
AMPH Flex®Reagent Cartridgeon the Dimension®	62	0
clinical chemistrysystem (cutoff 1000ng/mL )		102

Discrepants (ng/mL):

GC/MS	GC/MS	Dim	Syva
Meth	Amph	AMPH	30R
713	534	929	1134
494	844	922	aar

aar: above assay range, > 2000 ng/mL

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Comparison to Reference Method

GC/MS

(cutoff ≥ 500 ng/mL amphetamine

≥ 500 ng/mL metamphetamine and ≥ 200 ng/mL amphetamine)

AMPH Flex® Reagent Cartridge on Dimension® clinical chemistry system (cutoff 1000 ng/mL )

	-
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Discrepants (ng/mL):

GC/MS	GC/MS	Dim
Meth	Amph	AMPH
1223	118	1264
1209	127	1347
1112	172	1395
1183	174	1314
1213	177	1414
1194	180	1367
631	202	627
652	214	375
713	534	929
496	615	682
390	624	681
333	635	648
494	844	922
161	1032	770

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird-like figure, with three stylized lines representing its wings or body.

Public Health Service

APR - 8 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Andrea M. Tasker Senior Regulatory Affairs and Compliance Manger Dade Behring, Inc Chemistry/ Immunochemistry Glasgow Business Community; BLDG. 500 PO Box 6101 Newark, DE 19714

Re: K040133

Trade/Device Name: Dimension® Urine Amphetamine/ Methamphetamine Screen Flex® reagent cartridge (DF91B) Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine Test System Regulatory Class: Class II Product Code: DKZ Dated: January 20, 2004 Received: January 21, 2004

Dear Ms. Tasker :

We have reviewed vour 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 enclosurc) 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 complics 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); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820).

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Page 2

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 predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Jean M. Cooper, MS, DVM.

Yean M. Cooper, MS, D.V.M. 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 Statement

Device Name:

K040133

Dimension@ Urine Amphetamine/Methamphetamine Screen Flex® reagent cartridge (DF91B)

Indications for Use:

The AMPH Flex® reagent cartridge used on the Dimension® clinical chemistry system provides reagents for an in virro diagnostic test intended for the qualitative and semi-quantitative determination of amphetamines in human urine using a cutoff of either 300, 500 or 1000ng/mL. Measurements obtained with the AMPH method are used in the diagnosis and treatment of amphetamines use or overdose.

Jm. T

Andrea M. Tasker Regulatory Affairs and Compliance Manager

January 20, 2004

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109)

Over-the-counter Use (Optional format 1-2-96)

Carol Benson
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

stnka K040133

Page #

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).