The CEDIA® N-acetylprocainamide 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, N-acetylprocainamide in the sample competes with analyte conjugated to one inactive frayment of B-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed.

AI/ML Overview

The Boehringer Mannheim Corporation's CEDIA® N-acetylprocainamide Assay is a homogeneous enzyme immunoassay for the quantitative determination of N-acetylprocainamide in human serum and plasma. The study aimed to demonstrate its substantial equivalence to the predicate device, the Abbott TDx® N-acetylprocainamide Assay (K830206).

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the comparison to the predicate device. The performance characteristics of the CEDIA® Assay are presented and compared to those of the Abbott TDx® Assay.

Feature	Acceptance Criteria (Implied by Predicate Performance)	Reported CEDIA® N-acetylprocainamide Performance
Precision (Modified NCCLS)	Comparable to Abbott TDx® (e.g., %CV, mean values)
Level 1 Within run mean (%CV)	4.06 (3.3%)	1.91 (5.84%)
Level 2 Within run mean (%CV)	9.18 (1.7%)	4.41 (3.35%)
Level 3 Within run mean (%CV)	23.80 (2.3%)	10.75 (2.29%)
Level 1 Total mean (%CV)	4.06 (3.1%)	1.91 (7.35%)
Level 2 Total mean (%CV)	9.18 (2.4%)	4.41 (4.08%)
Level 3 Total mean (%CV)	23.80 (5.5%)	10.75 (2.87%)
Lower Detection Limit	0.6 µg/dL	0.6 µg/dL
Linearity	0.0 - 30.0 µg/dL	0.6 - 30 µg/dL
Method Comparison (vs. Predicate)	r = 0.986 (y = 1.06x - 0.60)	r = 0.994 (y = 1.04x + 0.21) (Least Squares)
		r = 0.9940 (y = 1.04x + 0.18) (Deming's)
Interfering Substances (No interference at:)
Bilirubin	15 mg/dL	66 mg/dL
Hemoglobin	1000 mg/dL	1000 mg/dL
Lipemia	1200 mg/dL	1200 mg/dL
Total Protein	9.5 mg/dL	13 g/dL
Rheumatoid Factor	N/A	85 IU/mL
Specificity (% Cross-reactivity)
Procainamide	None detected	0.1
Desethyl-N-Acetyl-procainamide	18.2	21.7
Desethyl-procainamide	Not tested	0.1

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

Precision: For precision studies, 120 measurements were performed for each of three levels (Level 1, Level 2, Level 3) for the CEDIA® assay. This is comparable to the 120 measurements for each of three levels reported for the predicate TDx assay.
Method Comparison: A sample size of N=125 was used for the method comparison of the CEDIA® Assay against the Abbott TDx® N-acetylprocainamide.
Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. It is implied to be a prospective study conducted by the manufacturer for regulatory submission.

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

This type of immunoassay device does not typically involve expert review for establishing ground truth in the same way as imaging or diagnostic interpretation devices. The ground truth for quantitative assays is established through reference methods or the performance of a well-established predicate device. In this comparison study, the Abbott TDx® N-acetylprocainamide Assay served as the reference for method comparison.

4. Adjudication Method for the Test Set

Not applicable for this type of quantitative immunoassay device. The results are numerical values, and direct comparison to a reference method or predicate device provides the basis for evaluation, not expert adjudication of classifications.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret results, and the AI's impact on reader performance is evaluated. The CEDIA® Assay is a quantitative laboratory test.

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

Yes, the performance data presented (precision, lower detection limit, linearity, method comparison, interfering substances, specificity) are all characteristics of the device itself, functioning in a standalone capacity (i.e., the "algorithm" or assay chemistry) without human intervention in the result determination beyond operating the instrument.

7. The Type of Ground Truth Used

The ground truth for the CEDIA® N-acetylprocainamide Assay's performance was established primarily through:

Comparison to a Predicate Device: The Abbott TDx® N-acetylprocainamide Assay served as the reference standard for method comparison.
Internal Validation Studies: Precision, linearity, lower detection limit, interfering substances, and specificity were likely determined through internal validation studies following standard laboratory practices and guidelines (e.g., NCCLS).

8. The Sample Size for the Training Set

The document does not specify a separate "training set" sample size. For an in vitro diagnostic device like this, the development process involves extensive research and development to optimize the assay's chemistry and components (reagents, enzyme fragments, antibodies). However, there isn't a "training set" in the machine learning sense. The assay's parameters are established through laboratory experimentation and optimization.

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

As there isn't a "training set" in the conventional machine learning sense, the concept of establishing ground truth for it doesn't directly apply. The "ground truth" for developing the assay's performance characteristics is intrinsically built into the chemical and biological principles of the assay and its optimization process by ensuring accurate and reliable measurement of N-acetylprocainamide concentrations. This involves:

Using known concentrations of N-acetylprocainamide for calibration and quality control.
Testing various reagent formulations to achieve desired sensitivity, specificity, and precision.
Comparing preliminary assay results against established reference methods or known concentrations.

Summary

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K963306

OCT 2 9 1996

17:58

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. Boehringer Mannheim Corporation Submitter 2400 Bisso Lane name, address, P.O. Box 4117 contact Concord, CA 94524-4117 (510) 674 - 0690, extension 8240 Contact Person: Betsy Soares-Maddox Date Prepared: October 10, 1996 2. Proprietary name: CEDIA® N-acetylprocainamide Assay Device name Common name: Homogeneous enzyme immunoassay for the determination of N-acetylprocainamide. Classification name: Enzyme immunoassay, N-acety|procainamide 3. The Boehringer Mannheim CEDIA® N-acetylprocainamide is substantially Predicate equivalent to other products in commercial distribution intended for similar device use. Most notably it is substantially equivalent to the currently marketed Abbott TDx® N-acety|procainamide Assay (K830206).

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510(k) Summary, Continued

Device Description The CEDIA® N-acetylprocainamide 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, N-acetylprocainamide in the sample competes with analyte conjugated to one inactive frayment of B-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed.

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510(k) Summary, Continued

5.Intended use	Immunoassay for the in vitro quantitative determination of N-acetylprocainamide in human serum and plasma.
6.Comparison topredicatedevice	The Boehringer Mannheim CEDIA® N-acetylprocainamide Assay issubstantially equivalent to other products in commercial distribution intendedfor similar use. Most notably it is substantially equivalent to the currentlymarketed Abbott TDx® N-acetylprocainamide Assay (K830206).
	The following table compares the CEDIA® N-acetylprocainamide Assaywith the predicate device, Abbott TDx® N-acetylprocainamide Assay.Specific data on the performance of the test have been incorporated into thedraft labeling in attachment 5. Labeling for the predicate device is providedin attachment 6.
	Similarities:
	•Intended Use: Immunoassay for the in vitro quantitative determinationof N-acetylprocainamide
	• Sample type: Serum and plasma
	•Assay range: 0.6 - 30 µg/mL

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Differences:

Comparison to
predicate
device cont.

Feature	CEDIA®N-acetylprocainamide	TDxN-acetylprocainamide
Reaction testprinciple	Spectrophotometric570 nm	Fluorescence Polarization
Instrumentrequired	Hitachi 911	Abbott TDx

Performance Characteristics:

Feature	CEDIA®N-acetylprocainamide			TDxN-acetylprocainamide
Precision	Modified NCCLS (µg/mL):			NCCLS (µg/mL):
Level	Level 1	Level 2	Level 3	Low	Mid	High
N	120	120	120	120	120	120
Within run mean	1.91	4.41	10.75	4.06	9.18	23.80
%CV	5.84	3.35	2.29	3.3	1.7	2.3
Total mean	1.91	4.41	10.75	4.06	9.18	23.80
%CV	7.35	4.08	2.87	3.1	2.4	5.5

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510(k) Summary, Continued

Performance Characteristics:

Comparison to
predicate
device, (cont.)

Feature	CEDIA®N-acetylprocainamide	TDxN-acetylprocainamide
LowerDetectionLimit	0.6 µg/dL	0.6 µg/dL
Linearity	0.6 - 30 µg/dL	0.0 - 30.0 µg/dL
MethodComparison	Vs Abbott TDxN-acetylprocainamideLeast Squaresy =1.04x + 0.21r=0.994N=125Deming's:y=1.04x + 0.18r=0.9940N=125	Vs Enzyme ImmunoassayN-acetylprocainamidey =1.06x - 0.60r=0.986N=96

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510(k) Summary, Continued

Performance Characteristics:

Comparison to
predicate
device, (cont.)

Feature	CEDIA®N-acetylprocainamide	TDxN-acetylprocainamide
Interferingsubstances	No interference at:(±10% of error)	No interference at:
Bilirubin	66 mg/dL	15 mg/dL
Hemoglobin	1000 mg/dL	1000 mg/dL
Lipemia	1200 mg/dL	1200 mg/dL
Total Protein	13 g/dL	9.5 mg/dL
RheumatoidFactor	85 IU/mL	N/A
Specificity	% Cross-reactivity	% Cross-reactivity
Procainamide	0.1	None detected
Desethyl-N-Acetyl-procainamide	21.7	18.2
Desethyl-procainamide	0.1	Not tested

Regulation Number and Section

§ 862.3320 Digoxin test system.

(a)
Identification. A digoxin test system is a device intended to measure digoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.(b)
Classification. Class II.