The CEDIA® Procainamide Assay is based on the bacterial enzyme ßgalactosidase, 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, procainamide in the sample competes with analyte conjugated to one inactive fragment of ß-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

This document describes the Boehringer Mannheim CEDIA® Procainamide Assay, a homogeneous enzyme immunoassay for the quantitative determination of procainamide in human serum and plasma. The information provided outlines the device's technical characteristics and performance compared to a predicate device, the Abbott TDx® Procainamide Assay.

Here's an analysis of the provided information regarding acceptance criteria and the supporting study:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct pass/fail thresholds in this summary. Instead, the performance characteristics of the CEDIA® Procainamide Assay are presented and implicitly compared to those of the predicate device (Abbott TDx® Procainamide Assay) to demonstrate substantial equivalence. The "acceptance criteria" can be inferred to be performance comparable to or better than the predicate device.

Feature	Acceptance Criteria (Inferred from Predicate Device Performance)	CEDIA® Procainamide Performance
Precision (Level 1 %CV)	Total %CV: ~5.4% (TDx Low)	Total %CV: 3.1%
Precision (Level 2 %CV)	Total %CV: ~4.2% (TDx Mid)	Total %CV: 3.0%
Precision (Level 3 %CV)	Total %CV: ~4.6% (TDx High)	Total %CV: 2.8%
Lower Detection Limit	≤ 0.1 µg/dL	0.4 µg/dL
Linearity Range	0.0 - 20.0 µg/dL	0.4 - 20 µg/dL
Method Comparison (r-value vs. predicate)	r ≥ 0.990 (TDx vs. EIA)	r = 0.9914 (CEDIA vs. TDx)
Bilirubin Interference	No interference at 15 mg/dL	No interference at 66 mg/dL
Hemoglobin Interference	No interference at 1000 mg/dL	No interference at 1000 mg/dL
Lipemia Interference	No interference at 1200 mg/dL	No interference at 1000 mg/dL
Protein Interference	No interference at 9.5 mg/dL	No interference at 6.5 g/dL Albumin, 10 g/dL IgG
N-Acetyl-procainamide Cross-reactivity	1.0 %	1.0 %
Desethyl-procainamide Cross-reactivity	15 %	16.3 %

Summary of Performance vs. Inferred Criteria:

Precision: The CEDIA® assay demonstrates better or comparable precision (lower %CV) across all levels compared to the predicate device.
Lower Detection Limit: The CEDIA® assay's lower detection limit (0.4 µg/dL) is higher than the predicate's (0.1 µg/dL), indicating potentially slightly less sensitivity at very low concentrations.
Linearity: The linearity range is similar, though the CEDIA's lower bound is 0.4 µg/dL compared to 0.0 µg/dL for the predicate.
Method Comparison: A strong correlation (r=0.9914) is shown between the CEDIA® assay and the predicate TDx assay, indicating good agreement.
Interfering Substances: The CEDIA® assay shows improved tolerance to bilirubin interference and comparable tolerance to hemoglobin and lipemia, with different protein interference concentrations reported.
Specificity/Cross-reactivity: The cross-reactivity for N-Acetyl-procainamide is identical, and for Desethyl-procainamide, it is very similar. Additional cross-reactivity for Procaine HCl is reported for CEDIA®.

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

Precision Test Set:
- N: 120 for each of 3 levels (Total N = 360 individual runs for CEDIA® assay precision testing).
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). This is a common omission in 510(k) summaries for in-vitro diagnostics where the studies are typically conducted internally by the manufacturer using controlled samples. It is implied to be prospective testing conducted for the submission.
Method Comparison Test Set:
- N: 122 samples for the comparison between CEDIA® Procainamide and Abbott TDx Procainamide.
- Data Provenance: Not explicitly stated. Likely prospective testing given the nature of method comparison studies.
Interfering Substances, Specificity/Cross-reactivity, Lower Detection Limit, Linearity: No specific N values are given for these tests, but they involve a series of experiments.

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

This type of information is generally not applicable for an in-vitro diagnostic (IVD) assay like the CEDIA® Procainamide Assay.

For IVDs that measure an analyte concentration, the "ground truth" is typically the reference method (e.g., mass spectrometry, or in this case, the predicate device if it's considered a reliable standard) or the known concentration within a manufactured control sample.
There are no "experts" establishing ground truth in the sense of image interpretation or clinical diagnosis. The "truth" is the measured chemical concentration.

4. Adjudication Method for the Test Set

This is not applicable for this type of IVD performance study. Adjudication methods (like 2+1, 3+1) are used in clinical trials or studies where human interpretation or consensus is required to establish a clinical endpoint or diagnosis, not for analytical performance testing of an enzyme immunoassay measuring circulating drug levels.

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

This is not applicable. An MRMC study is relevant for imaging devices or AI-assisted diagnostic tools where human interpretation is a key component. This document describes an automated laboratory assay for measuring drug levels, which does not involve human readers interpreting results in the same way an imaging study would.

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

Yes, this entire submission describes the standalone performance of the CEDIA® Procainamide Assay. This is an automated diagnostic test that provides a quantitative result based on its internal enzymatic reactions and spectrophotometric measurements. There isn't a "human-in-the-loop" in the sense of interpreting raw output, but rather a human operating the instrument and using the numeric result for clinical decision-making.

7. The Type of Ground Truth Used

The ground truth used for these analytical studies is:

Known concentrations: For precision, linearity, lower detection limit, interfering substances, and cross-reactivity, the "ground truth" is typically established by preparing samples with known, precise concentrations of the analyte (procainamide) and potential interferents. These concentrations are usually verified by a primary reference method if available.
Predicate Device/Reference Method: For method comparison, the "ground truth" for patient samples is essentially the result obtained from the predicate device (Abbott TDx® Procainamide Assay), which is considered the established method for comparison in this context. While not explicitly stated, it's implied that the Abbott TDx® assay served as the comparative standard. The TDx assay itself would have a foundation in comparison to a more definitive "gold standard" method when it was first cleared.

8. The Sample Size for the Training Set

The document does not mention a training set. This is because the CEDIA® Procainamide Assay is a biochemical assay, not a machine learning or AI model that requires a dedicated training set. The assay's performance is based on its chemical and enzymatic design, not on patterns learned from data.

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

As there is no "training set" in the context of this biochemical assay, this question is not applicable.

Summary

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用站 27 1996

Image /page/0/Picture/1 description: The image shows the logo for Boehringer Mannheim Diagnostics. The logo consists of a black square with the words "mannheim boehringer" written in white inside a white circle. To the right of the logo is the text "K962099 Diagnostics" written in black.

510(k) Summary

Introduction	According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence.
1.Submittername,address,contact	Boehringer Mannheim Corporation2400 Bisso LaneP.O. Box 4117Concord, CA 94524-4117(510) 674 - 0690, extension 8415Contact Person: Mary KoningDate Prepared: May 24, 1996
2.Device name	Proprietary name: CEDIA® Procainamide AssayCommon name: Homogeneous enzyme immunoassay for the determination ofprocainamide.Classification name: Enzyme immunoassay, procainamide
3.Predicatedevice	The Boehringer Mannheim CEDIA® Procainamide is substantially equivalentto other products in commercial distribution intended for similar use. Mostnotably it is substantially equivalent to the currently marketed Abbott TDx®Procainamide Assay (K834464).

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Device Description The CEDIA® Procainamide Assay is based on the bacterial enzyme ßgalactosidase, 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, procainamide in the sample competes with analyte conjugated to one inactive fragment of ß-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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Immunoassay for the in vitro quantitative determination of procainamide in న. Intended use human serum and plasma. The Boehringer Mannheim CEDIA® Procainamide 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 Abbott TDx® Procainamide Assay (K834464). The following table compares the CEDIA® Procainamide Assay with the predicate device. Abbott TDx® Procainamide 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: •Intended Use: Immunoassay for the in vitro quantitative determination of procainamide ·Sample type: Serum and plasma •Assay range: 0-420 µg/mL

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Comparison
to predicate device cont.

Differences:

Feature	CEDIA® Procainamide	TDx Procainamide
Reaction test principle	Spectrophotometric570 nm	Fluorescence Polarization
Instrument required	Hitachi 911	Abbott TDx

Performance Characteristics:

Feature	CEDIA® Procainamide			TDx Procainamide
Precision	Modified NCCLS (µg/mL)			Modified NCCLS (µg/mL):
Level	Level 1	Level 2	Level 3	Low	Mid	High
N	120	120	120	80	80	80
Within-Run	2.6	6.2	10.8	2.07	6.92	15.13
%CV	1.7	1.7	1.4	2.5	1.9	2.2
Total	2.6	6.2	10.8	2.07	6.92	15.13
%CV	3.1	3.0	2.8	5.4	4.2	4.6

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Performance Characteristics:

Comparison to predicate
device, (cont.) ,

Feature	CEDIA® Procainamide	TDx Procainamide
LowerDetectionLimit	0.4 µg/dL	0.1 µg/dL
Linearity	0.4 - 20 µg/dL (with adeviation from a linear line of±10%)	0.0 - 20.0 µg/dL
MethodComparison	Vs Abbott TDx ProcainamideLeast Squares$y =1.04x + 0.03$$r=0.9914$$SEE =0.42$$N=122$	Vs Enzyme ImmunoassayProcainamideLeast Squares$y =1.01x - 0.18$$r=0.990$$N=262$
	Deming's:$y =1.04x - 0.01$$r=0.9914$$SEE =0.30$$N=122$

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Performance Characteristics:

Comparison
to predicate device, (cont.)

Feature	CEDIA® Procainamide	TDx Procainamide
Interferingsubstances	No interference at:	No interference at:
Bilirubin	66 mg/dL	15 mg/dL
Hemoglobin	1000 mg/dL	1000 mg/dL
Lipemia	1000 mg/dL	1200 mg/dL
Protein	6.5 g/dL Albumin10 g/dL IgG	9.5 mg/dL
RheumatoidFactor	66 IU/ml	N/A
Specificity	% Cross-reactivity	% Cross-reactivity
N-Acetyl-procainamide	1.0	1.0
Desethyl-N-Acetyl-procainamide	0.1	None Detected
Desethylprocainamide	16.3	15
Procaine HCl	1.7	N/A

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.