Total Immunoglobulin E (IGE) reagent, when used in conjunction with IMMAGE® Immunochemistry Systems and IGE Calibrator, is intended for the quantitative determination of total human immunoglobulin E (IgE) in serum or plasma by rate turbidimetry.

Device Description

AI/ML Overview

The presented document is a 510(k) summary for the IMMAGE® Immunochemistry System Total Immunoglobulin E (IGE) Reagent and Calibrator, submitted by Beckman Coulter, Inc. It describes the device, its intended use, comparison to a predicate device, and a summary of performance data.

Here's an analysis of the acceptance criteria and study information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific thresholds for slope, intercept, r-value, or imprecision percentages. Instead, it presents the results of method comparison and imprecision studies as evidence of substantial equivalence to the predicate device. The implied acceptance is that the device's performance is comparable to or within expected variations for such assays, as demonstrated by the presented data.

Study Type	Metric	Acceptance Criteria (Implied)	Reported Device Performance	Comments
Method Comparison	Slope	Close to 1.0	1.06	Indicates good correlation between the IMMAGE system and the predicate Access Total IgE system.
	Intercept	Close to 0	2.75	A small intercept indicates minimal systematic bias.
	r (correlation coefficient)	High (e.g., >0.95)	0.991	Demonstrates strong linear correlation with the predicate method.
	n (sample size)	Adequacy for statistical significance	125	Generally considered a reasonable sample size for method comparison in diagnostic assays.
Imprecision	%CV (Within-Run)Level 1	Low (e.g., typically <10-15%)	5.8%	Indicates good reproducibility within a single run at a low IgE concentration.
	%CV (Within-Run)Level 2	Low	5.1%	Indicates good reproducibility within a single run at a medium IgE concentration.
	%CV (Within-Run)Level 3	Low	5.2%	Indicates good reproducibility within a single run at a high IgE concentration.
	%CV (Total)Level 1	Low	6.7%	Reflects overall reproducibility, including run-to-run variability, at a low IgE concentration. Typically slightly higher than within-run.
	%CV (Total)Level 2	Low	6.3%	Reflects overall reproducibility at a medium IgE concentration.
	%CV (Total)Level 3	Low	7.3%	Reflects overall reproducibility at a high IgE concentration.

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

Test Set Sample Size:
- Method Comparison: n = 125 samples.
- Imprecision: For each of the three levels tested, n = 80 measurements (implying multiple replicates across multiple runs). The term "N" is used for the number of measurements, not distinct patient samples.
Data Provenance: The document does not explicitly state the country of origin of the data or whether the samples were retrospective or prospective. Given that it's a 510(k) submission to the FDA, it's highly probable the studies were conducted in the US or under comparable standards. "Serum or plasma" is mentioned for the intended use, indicating the biological sample type.

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

This type of information is not applicable to this device. The IMMAGE® Immunochemistry System is an in vitro diagnostic (IVD) device for quantitative determination of a biomarker (Total IgE). The "ground truth" for this kind of device is established by a reference method or through highly controlled, well-characterized samples, not by expert consensus or interpretation of images/clinical data. The predicate device (Access® Total IgE) serves as the reference for the method comparison, meaning its results are considered the "ground truth" for comparative purposes.

4. Adjudication Method for the Test Set

This is not applicable as the ground truth is established by a quantitative reference method (the predicate device) or by direct measurement against known standards, not by human interpretation requiring adjudication.

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 devices where human interpretation plays a significant role (e.g., radiology AI tools). The IMMAGE System is an automated in vitro diagnostic device that produces quantitative results directly.

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

Yes, the studies presented (method comparison and imprecision) represent standalone performance of the IMMAGE® Immunochemistry System. The device directly measures IgE levels in samples; there isn't a "human-in-the-loop" component in terms of result generation for these performance studies. The results are generated by the device itself.

7. The Type of Ground Truth Used

The ground truth used for the performance evaluation can be described as follows:

For Method Comparison: The results obtained from the predicate device (Access® Total IgE) were used as the comparative "ground truth" or reference. The goal was to show concordance between the new device and the established, legally marketed predicate.
For Imprecision: The "ground truth" refers to the expected concentration of IgE in the quality control samples or patient samples used for repeated measurements. These values are typically established through rigorous characterization or use of certified reference materials if available.

8. The Sample Size for the Training Set

The document does not provide information on the sample size for a training set. For IVD devices like this one, "training set" doesn't typically apply in the same way it does for machine learning algorithms. The development of such a system involves extensive R&D, reagent formulation, and analytical validation. However, specific "training sets" in the AI sense are not usually disclosed or relevant for traditional IVD device submissions. The performance data presented (method comparison, imprecision, linearity, stability) are part of the analytical validation, not a "training" or "test" set in an AI context.

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

As noted in point 8, the concept of a "training set" and its associated ground truth in the context of machine learning is generally not applicable to this type of traditional immunochemistry system. The "ground truth" during the development of such assays would involve highly characterized samples, reference materials, and established analytical chemistry principles to ensure the reagents and system accurately detect and quantify the analyte (IgE).

Summary

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1024210
FEB 24 2003

510(k) Summary IMMAGE® Immunochemistry System Total Immunoglobulin E Reagent (IGE) Reagent and Calibrator

1.0 Submitted By:

Annette Hellie Requlatory Affairs Manager Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-104 Brea, California 92822-8000 Telephone: (714) 993-8767 FAX: (714) 961-4123

2.0 Date Submitted:

December 19, 2002

3.0 Device Name(s):

3.1 Proprietary Names

IMMAGE® Immunochemistry System Total Immunoglobulin E (IGE) Reagent IMMAGE® Immunochemistry System IGE Calibrator

3.2 Classification Name

Immunoglobulins A, G, M, D, and E test system (21 CFR § 866.5510) Calibrator (21 CFR § 862.1150)

4.0 Predicate Device:

Candidate(s)	Predicate	Manufacturer	DocketNumber
IMMAGE SystemTotal IGE	Access® Total IgE	BeckmanCoulter, Inc.	K930984

5.0 Description:

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6.0 Intended Use:

Clinical Significance:

IgE is a member of the immunoglobulin family of proteins that was first described in the 1960's. IgE. like all immunodlobulins, is produced by plasma cells in response to antigenic stimuli. IgE is unique however in certain structural aspects and the role it plays in allergic diseases.

Measurement of total serum IgE is often used as a tool in the diagnosis and management of atopic diseases such as asthma, hay fever, atopic dermatitis and urticaria. It has been used to distinguish atopic from non-atopic individuals presenting allergy-like symptoms. In addition, studies have also shown that increased levels of IgE in cord blood and infants may be predictive of future atopic tendencies.

Normal levels of circulating IgE are extremely low in comparison to other immunoqlobulins. Levels of IgE at birth are almost undetectable but increase in non-allergic adults. Elevated levels are commonly seen in cases of allergic diseases, parasitic infections, pulmonary aspergillosis, Wiskott-Aldrich Syndrome, and myeloma.

Serum IqE levels may vary as a result of diet, genetic background, geographical location and other factors. It is therefore recommended that total IqE measurements be used in conjunction with other clinical tests when establishing diagnoses.

7.0 Comparison to Predicate(s):

The following table shows similarities and differences between the predicates identified in Section 4.0 of this summary.

	Similarities
IMMAGE SystemTotal IGE	Intended Use	Same as Access Total IgE
	Liquid stable reagent
	Antibody (mousemonoclonal)
	Differences
IMMAGE SystemTotal IGE	Methodology	The IMMAGE uses rate nephelometry andthe Access uses chemiluminescentimmunoassay
	Measuring range	0.25-3000 IU/mL for Access5.0 - 500 IU/mL (initial dilution) up to30,000 (extended dilution) for IMMAGE

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Summary of Performance Data: 8.0

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison, stability, linearity, and imprecision experiments.

Analyte	Slope	Intercept	r	n	Predicate Method
IMMAGETotal IGE	1.06	2.75	0.991	125	Access Total IgE

Method Comparison Study Results

Sample	Mean (mg/dL)	S.D. (mg/dL)	%C.V.	N
Within-Run Imprecision
Level 1	16.5	0.97	5.8	80
Level 2	145	7.4	5.1	80
Level 3	383	19.9	5.2	80
Total Imprecision
Level 1	16.5	1.11	6.7	80
Level 2	145	9.1	6.3	80
Level 3	383	28.1	7.3	80

IMMAGE System IGE Estimated Imprecision

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of a human figure.

Ms. Annette Hellie Regulatory Affairs Manager Beckman Coulter, Inc. 200 S. Kraemer Boulevard, W-104 P.O. Box 8000 Brea, California 92822-8000

FEB 24 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

024210
Trade/Device Name: IM
Rea
Regulation Number: 21 C
Regulation Name: Immu
Regulatory Class: II

FEB 2 4 2003

Re: K024210

Trade/Device Name: IMMAGE® Immunochemistry System Total Immunoglobulin E Reagent (IGE) Reagent and Calibrator Regulation Number: 21 CFR § 866.5510 Regulation Name: Immunoglobulins A, G, M, D, and E Test System Regulatory Class: II Product Code: DGC Dated: February 11, 2003 Received: February 12, 2003

Dear Ms. Hellie:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate 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) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions 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 (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 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.

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If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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page ___ of _/

510(k) Number (if known): K02 42 /O

Device Name: IMMAGE® Immunochemistry System Total Immunoglobulin E Reagent (IGE) Reagent and Calibrator

Indications for Use:

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (per 21 CFR 801.109)	✓
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Over-the-Counter Use
Optional Format 1-2-96

J. P. Reave for J. Bautista
(Division Sign-Off)
Division of Clinical Laboratory Devices

510(k) Number	1C054210
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Beckman Coulter, Inc., Section 510(k) Notification IMMAGE® Immunochemistry System Total Immunoglobulin E (IGE) IGE510K_Section1.doc, December 2002

Regulation Number and Section

§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.

(a)
Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.(b)
Classification. Class II (performance standards).