The CEDIA® DAU EDDP Assay is a homogeneous enzy me immunoassay for the in vitro qualitative and semiquantitative determination of EDDP in human urine on automated clinical chemistry analy zers. Measurements are used as an aid in the diagnosis and treatment of methadone use or overdose.

Device Description

Homogeneous enzyme immunoassay for the determination of EDDP levels in urine.

AI/ML Overview

The provided text describes the Boehringer Mannheim CEDIA® DAU EDDP Assay, a homogeneous enzyme immunoassay for determining EDDP levels in human urine. The information presented is part of a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device rather than a comprehensive study report with detailed acceptance criteria and standalone performance.

Here's an analysis of the available information against your requested points:

1. Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in the traditional sense of a predefined threshold that the device must meet to be considered successful. Instead, it presents performance characteristics (Precision, Qualitative Sensitivity, Rate Separation, Accuracy, and Specificity) and compares them to a predicate device and/or a reference method (HPLC). The implicit "acceptance" is based on demonstrating comparable or improved performance relative to the predicate device or established analytical methods.

Since explicit acceptance criteria are not provided, the table below lists the reported performance data for the CEDIA® DAU EDDP Assay.

Performance Characteristic	Reported Device Performance (CEDIA® DAU EDDP Assay)
Precision
Intra assay 75 ng/ml	N=21, %CV=1.1
Intra assay 100 ng/ml	N=21, %CV=1.0
Intra assay 125 ng/ml	N=21, %CV=1.3
Qualitative Sensitivity	6.3 ng/mL (3 S.D.)
Rate Separation
Negative Calibrator/Low Control to Cutoff (75-100 ng/mL)	19.4 mAU/min
Cutoff to High Calibrator/Control (100-125 ng/mL)	13.2 mAU/min
Accuracy (at 100 ng/mL Cutoff)
Relative Sensitivity vs. DRI EIA	81.6%
Relative Specificity vs. DRI EIA	95.1%
Relative Sensitivity vs. HPLC	95.4%
Relative Specificity vs. HPLC	98.2%
Specificity (Conc. which gives a positive result)
EDDP	100 ng/mL
EMDP (Obs. ng/ml)	7.4 ng/mL (% Cross-reactivity: 0.004)
Methadone (Obs. ng/ml)	98.6 ng/mL (% Cross-reactivity: 0.016)

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

Sample Size for Test Set:
- For Precision: N=21 for each of the three concentration levels (75 ng/ml, 100 ng/ml, 125 ng/ml).
- For Accuracy (Relative Sensitivity/Specificity): The document mentions comparisons to the DRI EIA and HPLC. It does not specify the number of samples (cases) used for these comparisons. It only provides the resulting percentages.
- For Specificity (Cross-reactivity): The specific number of samples for each interfering substance is not explicitly stated, nor is the methodology (e.g., spike-recovery studies).
Data Provenance: The document does not provide information on the country of origin of the data or whether the studies were retrospective or prospective.

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

This specific submission (510(k) summary) does not involve human experts establishing ground truth for image interpretation or clinical diagnosis. The "ground truth" for this in-vitro diagnostic device (immunoassay) is established by:

Reference Methods: The predicate device (DRI Methadone Metabolite EIA) and an analytical gold standard (HPLC - High-Performance Liquid Chromatography).
Known Concentrations: Precision studies use samples with known target concentrations (e.g., 75 ng/ml). Specificity studies involve known concentrations of potential interfering substances (e.g., EMDP, Methadone).

Therefore, there were no human "experts" in the sense of radiologists or pathologists establishing ground truth as might be seen in imaging studies.

4. Adjudication Method for the Test Set

Not applicable. As described above, the ground truth is based on analytical reference methods and known chemical concentrations, rather than human review or consensus that would require an adjudication method.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for devices that assist human readers (e.g., AI in radiology). The CEDIA® DAU EDDP Assay is an in-vitro diagnostic (IVD) assay that directly measures a substance in urine; it does not involve human readers interpreting results in a way that would be augmented by AI.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, the performance data presented (Precision, Qualitative Sensitivity, Rate Separation, Accuracy, Specificity) for the CEDIA® DAU EDDP Assay are standalone performance of the assay itself. Since it's a chemical immunoassay, it inherently operates without "human-in-the-loop" interpretation in the AI context. The results are quantitative or semi-quantitative measurements directly output by the analytical equipment.

7. Type of Ground Truth Used

The types of ground truth used are:

Analytical Reference Method (HPLC): For Accuracy (Relative Sensitivity and Specificity), comparison was made against HPLC, which serves as a highly accurate and precise reference method for EDDP quantification.
Predicate Device (DRI Methadone Metabolite EIA): For Accuracy (Relative Sensitivity and Specificity), comparison was also made against another commercially available and legally marketed device.
Known Concentrations: For Precision and Specificity, the ground truth is established by preparing samples with known, precise concentrations of the analyte (EDDP) or potential interfering substances (EMDP, Methadone).

8. Sample Size for the Training Set

The document does not provide information about a "training set" for the device. As an immunoassay, this device relies on chemical reactions and optical detection, not a machine learning algorithm that typically requires a training set. If there were method development or optimization studies, those details are not part of this 510(k) summary.

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

Not applicable, as there is no mention of a "training set" in the context of an AI/machine learning algorithm for this immunoassay.

Summary

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BOEHRINGER MANN

.........

1/14/98 14:23 FAX 510 225 0654 BOEHRINGER MANN

MAY 26 1998 K980746

510(k) Summary

Introduction According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.

1) Submitter name, address, contact	Boehringer Mannheim Corporation4300 Hacienda DrivePleasanton, CA 94588-2722(510) 730-8240Fax: (510) 225-0654
	Contact Person: Betsy Soares-MaddoxDate Prepared: February 24, 1998
2) Device name	Proprietary name: CEDIA ® DAU EDDP AssayCommon name: Homogeneous enzyme immunoassay for the determination of EDDP levels in urine.Classification name: Methadone test system
3) Predicate device	We claim substantial equivalence to the Methadone Metabolite Enzyme Immunoassay (K931780) manufactured by Diagnostic Reagents, Inc.

Continued on next page

Boehringer Mannheim Corporation CEDIA DAU EDDP Assay page 25

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510(k) Summary, Continued

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510(k) Summary, Continued

The Boehringer Mannheim CEDIA® DAU EDDP Assay is substantially 6) Comparison equivalent to other products in commercial distribution intended for similar to predicate use. Most notably it is substantially equivalent to the currently marketed device Methadone Metabolite Enzyme Immunoassay (K931780) manufactured by Diagnostic Reagents, Inc (DRI). The following table compares the CEDIA® DAU EDDP Assay with the

predicate device, Methadone Metabolite Enzyme Immunoassay. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device in provided in attachment 6.

Similarities:

Both assays are for the qualitative and semi-quantitative determination of . EDDP levels in human urine.
Both assays utilize a monoclonal antibody. .
Both are enzyme immunoassays. .
Both assays may be used on the same instrumentation. .
Both assays have a similar assay range. .

Differences:

The two assays have different cutoff concentrations. .
Continued on next page

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510(k) Summary, Continued

Performance Characteristics: 6) Comparison to predicate device, (cont.)

Feature	DRI Methadone Metabolite EIA			CEDIA® DAU EDDP
Precision	Intra assay			Intra assay
Concentration LevelN%CV	Negative100.1	300 ng/ml100.1	2000 ng/ml100.3	75 ng/ml211.1	100 ng/ml211.0	125 ng/ml211.3
QualitativeSensitivity	75 ng/mL (2 S.D.)			6.3 ng/mL (3 S.D.)
Rate Separation
Negative Calibratoror Low Control toCutoff	18 mAU/min(0-300 ng/mL)			19.4 mAU/min(75-100 ng/mL)
Cutoff to HighCalibrator or Control	81 mAU/min(300-2000 ng/mL)			13.2 mAU/min(100-125 ng/mL)
Accuracy	300 ng/mL Cutoff:			100 ng/mL Cutoff:
Relative SensitivityRelative Specificity	Not reportedNot reported			vs. DRI EIA81.6%95.1%		vs. HPLC95.4%98.2%
Specificity		Concentration which gives apositive result (ng/mL)		Conc.(ng/mL)	[EDDP]Obs. ng/ml	% Cross-reactivity
EDDP		300		100	100	100
EMDP		400		200000	7.4	0.004
Methadone		5000		600000	98.6	0.016

Boehringer Mannheim Corporation CEDIA DAU EDDP Assay page 28

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Image /page/4/Picture/2 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features the department's name encircling a symbol. The symbol is a stylized representation of a bird or eagle, with three overlapping lines forming its body and wings. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA".

MAY 26 1998

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Julie A. Smith Boehringer Mannheim Corporation 4300 Hacienda Drive P.O. Box 9002 Pleasanton, California 94566-0900

K980746 Re: CEDIA® EDDP® Assay Requlatory Class: II DJR Product Code: Dated: April 24, 1998 Received: April 28, 1998

Dear Ms. Smith:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act 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 (Premarket Approval), it may be subject to such additional controls. Existing major requlations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ਨਾ substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact. the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

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 for information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Gutman

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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510(k) Number (if known): N/A

Device Name: CEDIA® DAU EDDP Assay

Indications For Use:

	Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use	OR	Over-The-Counter Use
(Per 21 CFR 801.109)		(Optional Format 1-2-96)

510(k) Number _

(Division Sign-Off)
Division of Clinical Laboratory Devices

Regulation Number and Section

§ 862.3620 Methadone test system.

(a)
Identification. A methadone test system is a device intended to measure methadone, an addictive narcotic pain-relieving drug, in serum and urine. Measurements obtained by this device are used in the diagnosis and treatment of methadone use or overdose and to determine compliance with regulations in methadone maintenance treatment.(b)
Classification. Class II (special controls). A methadone 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).