The Modified CEDIA DAU Benzodiazepine Assay is a homogeneous enzyme immunoassay for the qualitative and semi-quantitative assay of benzodiazepines in human urine. Measurements are used as an aid in the diagnosis and treatment of benzodiazepine use or overdose.

Device Description

The modified CEDIA® DAU Benzodiazepine Assay is an in-vitro enzyme immunoassay used for the qualitative and homogeneous semiquantitative measurement of benzodiazepines in urine. It is based on competitive binding concepts employing benzodiazepine derivative labeled (ß-galactosidase) competing with sample enzymatic fragments benzodiazepines for the benzodiazepine-specific antibody. Using recombinant DNA techniques, the B-galactosidase molecule has been split into two totally inactive polypeptide subunits called enzyme acceptor and enzyme donor. A benzodiazepine derivative has been covalently linked to the enzyme donor in a manner that does not prevent spontaneous reassociation of the subunits to vield active B-galactosidase enzyme. Benzodiazepine-specific antibody, by binding to the benzodiazepine derivative on the enzyme donor will inhibit enzyme reassociation, thereby regulating the level of B-galactosidase formed. The amount of enzyme formed is proportional to the amount of benzodiazepines as monitored by the hydrolysis of the substrate chlorophenol red-B-D-galactopyranoside (CPRG). The optional b-Glucuronidase reagent, when added to the Enzyme Acceptor reagent and mixed with sample on the analyzer, hydrolyzes glucuronide metaboliotes of benzodiazepines, thereby increasing the recognition of samples containing benzodiazepine metabolites.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the CEDIA DAU Benzodiazepine Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Feature	Acceptance Criteria (Implied / Predicate Device)	Modified CEDIA DAU Benzodiazepine Assay Performance
Precision (Within-Run %CV)	Should be comparable to or better than predicate device (CEDIA DAU Benzodiazepine Assay)	0.8% - 0.9% (at 150, 200, 250 ng/mL)
Precision (Total %CV)	Should be comparable to or better than predicate device (CEDIA DAU Benzodiazepine Assay)	5.8% - 6.0% (at 150, 200, 250 ng/mL)
Sensitivity (LOD)	Should be comparable to or better than predicate device (CEDIA DAU Benzodiazepine Assay)	12.3 ng/mL (vs. 10.8 ng/mL for predicate)
Sensitivity (LOQ)	Should be comparable to or better than predicate device (CEDIA DAU Benzodiazepine Assay)	12.1 ng/mL (vs. 10.7 ng/mL for predicate)
Accuracy (vs. CEDIA Benzodiazepine Assay)	100.0% (Implied benchmark from comparison)	100.0%
Specificity	Should be comparable to or better than predicate device (CEDIA DAU Benzodiazepine Assay)	95.1% (vs. 99.1% for predicate)
Tolerance to Interfering Substances	Less than 10% error at specified concentrations	Less than 10% error at various specified concentrations (e.g., Acetone: 1 g/dL, Glucose: 3 g/dL)

Notes on Acceptance Criteria: The document primarily focuses on demonstrating substantial equivalence to a predicate device (CEDIA DAU Benzodiazepine Assay, K954626). Therefore, the "acceptance criteria" are largely implied by the performance of the predicate device, with the modified device needing to perform comparably or better, especially for new features like increased sensitivity to conjugated compounds. The "Accuracy" row explicitly states "Vs. CEDIA Benzodiazepine Assay 100.0%", suggesting this was a direct comparison for accuracy.

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

Sample Size: For precision, a sample size (N) of 120 was used for each concentration level (150, 200, 250 ng/mL) for both within-run and total precision across both the modified and predicate devices.
Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective. It only mentions that the data was "generated from modified CEDIA DAU Benzodiazepine assay used the ß-Glucuronidase application."

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

This information is not provided in the document. The study focuses on comparing the performance of the modified assay to a predicate device and other assay methods (like EMIT II), not on establishing a ground truth based on expert consensus for individual samples.

4. Adjudication Method for the Test Set

This information is not provided as the study design does not appear to involve adjudication of results from human readers. The data presented is from a chemical assay.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study was not conducted. This document describes an in-vitro diagnostic assay for benzodiazepines, not an imaging device or AI-assisted diagnostic tool that would involve human readers.

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

This device is a standalone diagnostic assay. The performance metrics presented (precision, sensitivity, specificity, interference) are all measures of the algorithm's (assay's) performance without human interpretation or intervention in the results generation.

7. The Type of Ground Truth Used

The ground truth for the performance evaluations (e.g., accuracy, sensitivity, specificity) appears to be established through comparison to other established predicate assays or laboratory standards.
- Accuracy: Evaluated "Vs. CEDIA Benzodiazepine Assay" (predicate device) and "Vs. EMIT II Benzodiazepine Assay". This suggests the results from these established methods served as a reference or "ground truth" for evaluating the new device's accuracy.
- Precision: Evaluated against "Modified NCCLS (mA/min) Cutoff Protocol," indicating a standardized laboratory methodology.
- Interfering Substances: Likely tested by spiking known concentrations of substances into samples and measuring the effect on assay results.

8. The Sample Size for the Training Set

This information is not applicable and not provided. This is an immunoassay, not a machine learning model that requires a "training set." The assay's performance is determined by its chemical reagents and reaction kinetics.

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

This information is not applicable as there is no "training set" for this type of in-vitro diagnostic assay.

Summary

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K9627354

DEC 1 0 1996

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Diagnostics

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 Corporation2400 Bisso LaneConcord, CA 94524(510) 674-0667
	Contact Person: Betsy Soares-Maddox
	Date Prepared: July 11, 1996
2) Device name	Proprietary name: CEDIA DAU Benzodiazepine Assay
	Common name: Homonogeneous enzyme immunoassay for the determination of benzodiazepine levels in urine.
	Classification name: Benzodiazepine test system
3) Predicate device	We claim substantial equivalence to the CEDIA DAU Benzodiazepine Assay (K954626)

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4) Device The modified CEDIA® DAU Benzodiazepine Assay is an in-vitro Description enzyme immunoassay used for the qualitative and homogeneous semiquantitative measurement of benzodiazepines in urine. It is based on competitive binding concepts employing benzodiazepine derivative labeled (ß-galactosidase) competing with sample enzymatic fragments benzodiazepines for the benzodiazepine-specific antibody. Using recombinant DNA techniques, the B-galactosidase molecule has been split into two totally inactive polypeptide subunits called enzyme acceptor and enzyme donor. A benzodiazepine derivative has been covalently linked to the enzyme donor in a manner that does not prevent spontaneous reassociation of the subunits to vield active B-galactosidase enzyme. Benzodiazepine-specific antibody, by binding to the benzodiazepine derivative on the enzyme donor will inhibit enzyme reassociation, thereby regulating the level of B-galactosidase formed. The amount of enzyme formed is proportional to the amount of benzodiazepines as monitored by the hydrolysis of the substrate chlorophenol red-B-D-galactopyranoside (CPRG). The optional b-Glucuronidase reagent, when added to the Enzyme Acceptor reagent and mixed with sample on the analyzer, hydrolyzes glucuronide metaboliotes of benzodiazepines, thereby increasing the recognition of samples containing benzodiazepine metabolites.

Intended u se

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Q) Comparison to predicate device

The Boehringer Mannheim modified CEDIA DAU Benzodiazepine Assay is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Boehringer Mannheim CEDIA DAU Benzodiazepine Assay (K954626).

The following table compares the modified CEDIA DAU Benzodiazepine Assay with the predicate device, CEDIA DAU Benzodiazepine Assay. Specific data on the performance of the test have been incorporated into the draft labeling in attachment 5. Labeling for the predicate device is provided in attachment 6.

Similarities:

· Both Assays use the same kit
· Both assays are used on the BM/Hitachi 717 analyzer using the same chemistry parameters

· Both assays are for qualitative and semiquantitative determination of benzodiazepines in urine.

Differences:

· Addition of B-Glucuronidase to the reconstituted Enzyme Acceptor reagent. (This component is sold separately.)

· Higher sensitivity to conjugated benzodiazepine compounds
· When B-Glucuronidase is utilized, only the 200 ng/mL cutoff is available.

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Comparison to predicate device, (cont.) Performance Characteristics: (note: data generated from modified CEDIA DAU Benzodiazepine assay used the ß-Glucuronidase application.)

Feature	Modified CEDIA DAUBenzodiazepine			CEDIA DAUBenzodiazepine
Precision	Modified NCCLS(mA/min):200 ng/mL Cutoff Protocol			Modified NCCLS(mA/min):200 ng/mL Cutoff Protocol
ConcentrationLevel	150	200	250	150	200	250
N	120	120	120	120	120	120
Within-Run	303.0	331.7	363.1	299.6	324.3	362.1
%CV	0.8	0.8	0.9	0.9	0.8	0.9
Total	303.0	331.7	363.1	299.6	324.3	362.1
%CV	5.9	6.0	5.8	3.5	3.5	3.5
Sensitivity (LOD)200 ng/mL Cutoff	12.3 ng/mL			10.8 ng/mL
Sensitivity (LOQ)200 ng/mL Cutoff	12.1 ng/mL			10.7 ng/mL
Accuracy200 ng/mL CutoffSensitivity	Vs. CEDIA BenzodiazepineAssay100.0%			Vs. EMIT IIBenzodiazepine Assay98.2%
Specificity	95.1%			99.1%

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Comparison
to predicate
device (cont.)

Feature	Modified CEDIA DAUBenzodiazepine	CEDIA DAUBenzodiazepine
Interferingsubstances	Less than 10% error at:	Less than 10% error at:
Acetone	1 g/dL	1 g/dL
Ascorbic Acid	0.15 g/dL	0.15 g/dL
Creatinine	0.5 g/dL	0.5 g/dL
Ethanol	1 g/dL	1 g/dL
Galactose	10 mg/dL	10 mg/dL
y-globulin	0.5 g/dL	0.3 g/dL
Glucose	3 g/dL	1.5 g/dL
Hemoglobin	0.3 g/dL	0.3 g/dL
Human SerumAlbumin	0.5 g/L	0.5 g/L
Oxalic Acid	0.1g/dL	0.1g/dL
Riboflavin	7.5 mg/dL	7.5 mg/dL
Sodium Chloride	6 g/dL	6 g/dL
Urea	4 g/dL	6 g/dL
Specificity	Multiple benzodiazepinecompounds	Multiple benzodiazepinecompounds

Regulation Number and Section

§ 862.3170 Benzodiazepine test system.

(a)
Identification. A benzodiazepine test system is a device intended to measure any of the benzodiazepine compounds, sedative and hypnotic drugs, in blood, plasma, and urine. The benzodiazepine compounds include chlordiazepoxide, diazepam, oxazepam, chlorzepate, flurazepam, and nitrazepam. Measurements obtained by this device are used in the diagnosis and treatment of benzodiazepine use or overdose and in monitoring levels of benzodiazepines to ensure appropriate therapy.(b)
Classification. Class II (special controls). A benzodiazepine 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).