The modified CEDIA® DAU PCP Assay is a homogeneous enzyme immunoassay for the in vitro qualitative and semiquantitative assay of PCPs in human urine. Measurements are used as an aid in the diagnosis and treatment of PCP use or overdose.

Device Description

The CEDIA DAU PCP assay uses recombinant DNA technology (US Patent No. 4708929) to produce a unique homogeneous enzyme immunoassay system. This assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically. In the assay, drug in the sample competes with drug conjugated to one inactive fragment of B-galactosidase for antibody binding site. If drug is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If drug is not present in the sample, antibody binds to drug conjugated on the inactive fragment, inhibiting the reassociation of inactive B-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are proportional to the amount of drug present in the sample.

AI/ML Overview

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

1. Table of Acceptance Criteria and Reported Device Performance

Feature	Acceptance Criteria (Implicit from Predicate & Comparison)	Modified CEDIA DAU PCP Performance (Test Device)	Predicate CEDIA DAU PCP Performance
Precision (25 ng/mL Cutoff, 19 Concentration Level)	At least equivalent to predicate (238.4 mA/min Total, 4.3% CV Total)	281.1 mA/min Total, 1.5% CV Total	238.4 mA/min Total, 4.3% CV Total
Precision (25 ng/mL Cutoff, 25 Concentration Level)	At least equivalent to predicate (276.4 mA/min Total, 5.3% CV Total)	323.1 mA/min Total, 1.5% CV Total	276.4 mA/min Total, 5.3% CV Total
Precision (25 ng/mL Cutoff, 31 Concentration Level)	At least equivalent to predicate (316.3 mA/min Total, 5.0% CV Total)	370.4 mA/min Total, 1.4% CV Total	316.3 mA/min Total, 5.0% CV Total
Qualitative Sensitivity (25 ng/mL Cutoff)	At least equivalent to predicate (1.7 ng/mL)	1.05 ng/mL	1.7 ng/mL
Semiquantitative Sensitivity (25 ng/mL Cutoff)	(Not explicitly stated for predicate in quantitative terms, but implied to be effective)	0.96 ng/mL	N/A (Not reported quantitatively for predicate)
Accuracy (25 ng/mL Cutoff Sensitivity)	At least equivalent to predicate (99.1% vs. Commercially available EIA Assay)	96.9% (Vs. CEDIA PCP Assay)	99.1% (Vs. Commercially available EIA Assay)
Specificity	100.0%	100.0%	100.0%
Interfering Substances (Acetone)	Less than 10% error at 1 g/dL	Less than 10% error at 1 g/dL	Less than 10% error at 1 g/dL
Interfering Substances (Ascorbic Acid)	Less than 10% error at 1.5 g/dL	Less than 10% error at 1.5 g/dL	Less than 10% error at 1.5 g/dL
Interfering Substances (Creatinine)	Less than 10% error at 0.5 g/dL	Less than 10% error at 0.5 g/dL	Less than 10% error at 0.5 g/dL
Interfering Substances (Ethanol)	Less than 10% error at 1 g/dL	Less than 10% error at 1 g/dL	Less than 10% error at 1 g/dL
Interfering Substances (Galactose)	Less than 10% error at 10 mg/dL	Less than 10% error at 10 mg/dL	Less than 10% error at 10 mg/dL
Interfering Substances (y-globulin)	Less than 10% error at 0.5 g/dL	Less than 10% error at 0.5 g/dL	Less than 10% error at 0.5 g/dL
Interfering Substances (Glucose)	Less than 10% error at 3 g/dL	Less than 10% error at 3 g/dL	Less than 10% error at 3 g/dL
Interfering Substances (Hemoglobin)	Less than 10% error at 0.3 g/dL	Less than 10% error at 0.3 g/dL	Less than 10% error at 0.3 g/dL
Interfering Substances (Human Serum Albumin)	Less than 10% error at 0.5 g/L	Less than 10% error at 0.5 g/L	Less than 10% error at 0.5 g/L
Interfering Substances (Oxalic Acid)	Less than 10% error at 0.1g/dL	Less than 10% error at 0.1g/dL	Less than 10% error at 0.1g/dL
Interfering Substances (Riboflavin)	Less than 10% error at 7.5 mg/dL	Less than 10% error at 7.5 mg/dL	Less than 10% error at 7.5 mg/dL
Interfering Substances (Sodium Chloride)	Less than 10% error at 6 g/dL	Less than 10% error at 6 g/dL	Less than 10% error at 6 g/dL
Interfering Substances (Urea)	Less than 10% error at 3 g/dL (for predicate, modified specifies 5 g/dL)	Less than 10% error at 5 g/dL	Less than 10% error at 3 g/dL
Specificity (PCP Compounds)	Multiple PCP compounds detected	Multiple PCP compounds detected	Multiple PCP compounds detected

Explanation of Acceptance Criteria: The acceptance criteria are implicitly defined by demonstrating "substantial equivalence" to the predicate device (CEDIA DAU PCP Assay, K935650). This means the new device's performance characteristics should be comparable to or better than the predicate's, with any differences not raising new questions of safety or effectiveness. For precision, the modified device shows better or equivalent %CV. For sensitivity, the modified device shows better performance. For accuracy, it's compared to the predicate, which in turn was compared to a commercially available EIA. Interfering substances are shown to have similar, acceptable interference levels.

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

Precision (Test Set):
- For the modified CEDIA DAU PCP, at each concentration level (19, 25, 31 ng/mL): N = 126.
- For the predicate CEDIA DAU PCP, at each concentration level (19, 25, 31 ng/mL): N = 120.
Accuracy (Test Set): The sample size for the accuracy comparison (96.9% sensitivity for the modified device vs. the predicate, and 99.1% for the predicate vs. a commercial EIA) is not explicitly stated in terms of number of samples.
Data Provenance: The document does not specify the country of origin of the data. It is a submission to the FDA, suggesting the studies were conducted to meet US regulatory requirements, but the origin of the samples is not mentioned. The studies appear to be prospective, as performance characteristics are being generated for a new device.

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 studies described are analytical performance studies of an in vitro diagnostic device, not studies involving human interpretation or clinical outcomes adjudicated by experts.

4. Adjudication Method for the Test Set

This information is not applicable as the studies are analytical and do not involve human adjudication of results. The results are quantitative measurements and comparisons of sensitivity, specificity, and precision.

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, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in vitro diagnostic assay, not an 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

The entire study described is a standalone performance evaluation of the device (assay), without human-in-the-loop performance being a relevant factor for this type of test. The device itself performs the measurement.

7. The Type of Ground Truth Used

The ground truth for the performance characteristics appears to be established by:

Analytically determined concentrations: For precision, samples were prepared at specific concentrations (19, 25, 31 ng/mL).
Comparison to a predicate device: For accuracy, the modified device was compared against the existing CEDIA DAU PCP Assay, and the predicate itself was compared against a "Commercially available EIA Assay." This implies that the predicate assay's results, or the commercial EIA's results, served as a reference standard (ground truth) for establishing accuracy.
Known concentrations of interfering substances and PCP compounds: For interfering substances and specificity, the ground truth would be the known concentration of the substance and the presence of specific PCP compounds.

8. The Sample Size for the Training Set

This information is not applicable/not provided. The CEDIA DAU PCP Assay is a homogeneous enzyme immunoassay based on recombinant DNA technology. It is not an AI/machine learning algorithm that requires a "training set" in the conventional sense. The "training" of this system is inherent in its biochemical design and optimization during development, rather than through data-driven machine learning.

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 device in the context of machine learning. The principles of its operation (enzyme immunoassay) are based on established biochemical reactions, and optimization would involve laboratory experiments to determine optimal reagents and conditions, rather than a "ground truth" derived from expert consensus or pathology on a training dataset.

Summary

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SEP 2 2 1997

;

K972963

BOEHRINGER

MANNHEIM

CORPORATION

510(k) Summary

![boehringer mannheim logo](boehringer mannheim logo.png)

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 Corporation 2400 Bisso Lane Concord, CA 94524 (510) 674-0667 Fax: (510) 687-1850 Contact Person: Yvette Lloyd
	Date Prepared: August 8, 1997
2) Device name	Proprietary name: CEDIA DAU PCP Assay Common name: Homonogeneous enzyme immunoassay for the determination of PCP levels in urine. Classification name: PCP test system
3) Predicate device	We claim substantial equivalence to the CEDIA DAU PCP Assay (K935650).

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BOEHRI Summarv. Continued ORPORATION

Image /page/1/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo consists of a black square with the word "mannheim" written vertically on the left side. Inside the square is a white circle with the word "boehringer" written inside it. The text is in a simple, sans-serif font.

The CEDIA DAU PCP assay uses recombinant DNA technology (US Patent 4) Device Description No. 4708929) to produce a unique homogeneous enzyme immunoassay sy stem. This assay is based on the bacterial enzyme ß-galactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically . In the assay, drug in the sample competes with drug conjugated to one inactive fragment of B-galactosidase for antibody binding site. If drug is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If drug is not present in the sample, antibody binds to drug conjugated on the inactive fragment, inhibiting the reassociation of inactive B-galactosidase fragments, and no active enzyme is formed. The amount of active enzyme formed and resultant absorbance change are proportional to the amount of drug present in the sample.

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

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Summary, Continued

Image /page/2/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo consists of a white circle with the word "boehringer" inside it. To the left of the circle, the word "mannheim" is written vertically. The background of the logo is black.

() Comparison to predicate device

The Boehringer Mannheim modified CEDIA DAU PCP 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 PCP Assay (K935650).

The following table compares the modified CEDIA DAU PCP Assay with the predicate device, CEDIA DAU PCP 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.

Similaritics:

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

· Same chemistry parameters

Differences:

· The modified CEDIA DAU PCP assay uses a different antibody and EDconjugate

· The modified CEDIA DAU PCP assay has lower crossreactivity to diphenhydramine.

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Summary, Continued ORATION

Image /page/3/Picture/1 description: The image shows a logo with the word "mannheim" written vertically on the left side. To the right of the word is a circle with the word "boehringer" inside. The background of the logo is black, and the text and circle are white.

Performance Characteristics:

Comparison
to predicate

device, (cont.)

Feature	Modified CEDIA DAU PCP	CEDIA DAU PCP
Precision	Modified NCCLS(mA/min):25 ng/mL CutoffProtocol	Modified NCCLS(mA/min):25 ng/mL CutoffProtocol
ConcentrationLevel	19	19
N	126	120
Within-Run	281.1	238.4
%CV	0.7	1.0
Total	281.1	238.4
%CV	1.5	4.3
ConcentrationLevel	25	25
N	126	120
Within-Run	323.1	276.4
%CV	0.7	1.2
Total	323.1	276.4
%CV	1.5	5.3
ConcentrationLevel	31	31
N	126	120
Within-Run	370.4	316.3
%CV	0.6	1.1
Total	370.4	316.3
%CV	1.4	5.0
QualitativeSensitivity25ng/mL Cutoff	1.05 ng/ml	1.7 ng/ml
SemiquantitativeSensitivity25ng/mL Cutoff	0.96 ng/ml	N/A
Accuracy	Vs. CEDIA PCP Assay	Vs. Commercially available EIA Assay
25 ng/mL CutoffSensitivity	96.9%	99.1
Specificity	100.0%	100.0%

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BOEHRIN (k) Summary, Continued CORPORATION

Image /page/4/Picture/1 description: The image shows a logo for Boehringer Mannheim. The logo consists of a black square with a white circle inside. The word "boehringer" is written in white inside the circle. The word "mannheim" is written vertically in white on the left side of the square.

Comparison

to predicate
device (cont.)

Feature	Modified CEDIA DAUPCP	CEDIA DAU PCP
Interferingsubstances	Less than 10% error at:	Less than 10% error at:
Acetone	1 g/dL	1 g/dL
Ascorbic Acid	1.5 g/dL	1.5 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	0.5 g/dL
Glucose	3 g/dL	3 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	5 g/dL	3 g/dL
Specificity	Multiple PCP compounds	Multiple PCP compounds

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Image /page/5/Picture/2 description: The image is a black and white seal for the Department of Health & Human Services USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. In the center of the seal is a stylized image of three human profiles facing to the right, with flowing lines beneath them.

SEP 22 1997

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Yvette Lloyd .Regulatory Affairs Specialist Boehringer Mannheim Corporation 2400 Bisso Lane P.O. Box 4117 94524-4117 Concord, California

Re : K972963 CEDIA DAU PCP Assay Requlatory Class: II Product Code: LCM Dated: August 8, 1997 Received: August 11, 1997

Dear Ms. Lloyd:

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, Druq, 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, qood 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 regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. ਰੇ 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 Reqister. 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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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 to
premarket notification" (21 CFR 807.97). Other general 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 Bitman

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

lxvice Name: CEDIA® DAU PCP Assay

Indications For Use:

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

(Division Sign-Off
Division of Clinic
510(k) Number. AK2963

Regulation Number and Section

N/A