For in vitro quantitative determination of immunoglobulin E in human serum and plasma. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Boehringer Mannheim Elecsys 1010 and 2010 immunoassay analyzers. Determination of total serum IgE is useful as an aid in the diagnosis of allergic disease.

Device Description

The Elecsys® IgE test is based on the sandwich principle of heterogeneous immunological complex formation. First Step: Biotinylated monoclonal antibodies (R1) and ruthenium labeled antibodies (R2), both specific for IgE, bind IgE present in the sample forming a sandwich complex Second Step: Microparticles coated with streptavidin (M) bind the biotin portion of the complex and are captured magnetically onto the surface of the electrode. Application of a voltage to the electrode induces chemiluminescent emission, which is measured by a photomultiplier.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Elecsys® IgE Test, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance:

Feature	Acceptance Criteria (Implied / Predicate Performance)	Reported Device Performance (Elecsys® IgE Test)
Precision		Within-Run %CV
	Within-Run %CV: ~2.1% at 102.7 IU/mL ~2.1% at 244.1 IU/mL ~2.8% at 375.4 IU/mL	3.6% at 5.18 IU/mL 2.1% at 105 IU/mL 2.8% at 197 IU/mL 3.2% at 398 IU/mL 2.4% at 1010 IU/mL
	Total %CV	Total %CV
	Total %CV: ~3.4% at 102.7 IU/mL ~3.4% at 244.1 IU/mL ~3.6% at 375.4 IU/mL	4.2% at 5.18 IU/mL 1.9% at 105 IU/mL 3.9% at 197 IU/mL 3.9% at 398 IU/mL 3.1% at 1010 IU/mL
Lower Detection Limit	1.44 IU/mL (Predicate)	0.10 IU/mL
Measuring Range	1.44 - 500 IU/ml (Predicate)	0.10 - 4000 IU/ml
Specificity	No cross-reactions with IgG, IgA, and IgM (Predicate)	No cross-reactivity with the immunoglobulins G, A, and M was detected.
Method Comparison	Evidence of strong correlation (e.g., r close to 1) with the predicate device.	Elecsys IgE vs Enzymun-Test IgE Passing/Bablok: y = -0.53 + 0.97x, r = 1.0, SD (md68) = 2.42, N = 188 Linear regression: y = -1.85 + 1.01x, r = 1.0, Sy.x = 5.86, N = 188
Interfering Substances	No interference at predicate's concentrations: Bilirubin <64.5 mg/dL Hemoglobin <1 g/dL Lipemia <1250 mg/dL Biotin <100 ng/mL	No interference at: Bilirubin: <37 mg/dL Hemoglobin: <1.1 g/dL Lipemia: <2200 mg/dL Biotin: <100 ng/mL

Interpretation of Acceptance Criteria:

The acceptance criteria are generally established by comparison to a legally marketed predicate device. The Elecsys® IgE Test aims to demonstrate "substantial equivalence" to the Enzymun-Test® IgE. This means its performance characteristics should be comparable to or better than the predicate, and any differences should not raise new questions of safety or effectiveness.

Precision: The Elecsys® IgE Test shows comparable or slightly higher %CVs at some points compared to the predicate's reported precision, but also significantly lower %CVs at higher concentrations. The overall precision performance across a wider range of concentrations is provided.
Lower Detection Limit & Measuring Range: The Elecsys® device demonstrates a significantly improved lower detection limit and a substantially wider measuring range compared to the predicate, which would generally be seen as a positive improvement.
Specificity: Both devices report no cross-reactivity with other common immunoglobulins, meeting this criterion.
Method Comparison: The high correlation coefficients (r = 1.0) for both Passing/Bablok and Linear Regression indicate excellent agreement between the Elecsys® IgE Test and the predicate Enzymun-Test® IgE, demonstrating that the new device measures IgE levels similarly to the established method. The 'N = 188' indicates the sample size used for this comparison.
Interfering Substances: The Elecsys® IgE Test demonstrates non-interference at comparable or higher concentrations for some interfering substances (Hemoglobin, Lipemia) and a slightly lower threshold for Bilirubin, while matching the Biotin threshold of the predicate. This demonstrates robust performance in the presence of common interferents.

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

Test Set Sample Size: For the method comparison study, N = 188 samples were used.
Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. It is implied to be data collected to characterize the performance of the new device against the predicate.

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

This is an in vitro diagnostic (IVD) device for quantitative determination of IgE levels. The "ground truth" for the test set (the 188 samples) would be the IgE values obtained using the predicate device (Enzymun-Test® IgE) or a reference method. Therefore, human experts are not directly involved in establishing the ground truth in the same way they would be for image interpretation or clinical diagnosis. The "ground truth" is measured quantitatively by a validated assay.

4. Adjudication Method for the Test Set:

Not applicable as this is a quantitative IVD device. The "truth" is the measured IgE concentration, not a subjective interpretation requiring adjudication.

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. This is an in vitro diagnostic device, not an AI-assisted diagnostic tool that involves human readers interpreting cases. Therefore, an MRMC study is not relevant.

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

Yes. This is a standalone automated immunoassay. The Elecsys® IgE Test operates without human intervention in the measurement process, once the sample is loaded and the test initiated. Its performance characteristics (precision, detection limit, range, specificity, method comparison) are all reported as "standalone" performance.

7. The Type of Ground Truth Used:

The ground truth for evaluating the Elecsys® IgE Test's performance (specifically for the method comparison) was generated by comparison to a legally marketed predicate device (Enzymun-Test® IgE). This is a common practice for demonstrating substantial equivalence for IVD devices. The predicate device itself would have been calibrated against a WHO Standard (as stated in the document), which serves as the ultimate reference for IgE quantification.

8. The Sample Size for the Training Set:

This document is a 510(k) summary for a traditional immunoassay, not an AI/ML device. Therefore, the concept of a "training set" for an algorithm is not applicable. The device's performance is driven by its reagent formulation, instrument design, and chemical reaction principles, not by a trained algorithm.

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

Not applicable as there is no "training set" in the context of this traditional immunoassay.

Summary

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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.
Submittername, address,contact	Roche Diagnostics, doing business in the US as Roche Diagnostics9115 Hague RdIndianapolis, IN 46250(317) 576-3723
	Contact person: Priscilla A. Hamill
	Date prepared: December 2, 1998
Device name	Proprietary name: Elecsys® IgE Test
	Common name: IgE
	Classification name: Immunoglobulins A, G, M, D, and E immunologicaltest system
Predicatedevice	We claim substantial equivalence to the Boehringer Mannheim Enzymun-Test® IgE.
Devicedescription	The Elecsys® IgE test is based on the sandwich principle of heterogeneousimmunological complex formation.
	First Step: Biotinylated monoclonal antibodies (R1) and ruthenium labeledantibodies (R2), both specific for IgE, bind IgE present in the sample forminga sandwich complexSecond Step: Microparticles coated with streptavidin (M) bind the biotinportion of the complex and are captured magnetically onto the surface of theelectrode. Application of a voltage to the electrode induces chemiluminescentemission, which is measured by a photomultiplier.

02/04/99

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510(k) Summary, Continued

Intended use

Comparison to the predicate device

Similarities: The following table compares Boehringer Mannheim ® IgE Test with the predicate device. 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.

Feature	Elecsys® IgE Test	Enzymun-Test® IgE.
Intended use	For the quantitative determination of IgE in human serum and plasma on the Elecsys 1010 and 2010 immunoassay analyzers.	For the quantitative determination of IgE in human serum and plasma on automated immunoassay analyzers
Indications for use	An aid in the diagnosis of allergic diseases	An aid in the diagnosis of allergic diseases
Sample type	Human serum, plasma	Human serum, plasma
Assay reaction principle	Sandwich principle, Heterogeneous immunological complex formation	Sandwich principle, Heterogeneous immunological complex formation, ELISA
Standardized against	WHO Standard	WHO Standard

Continued on next page

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510(k) Summary, Continued

Comparison to the predicate device (cont.)

Differences: The following differences between Elecsys® IgE Test and the predicate device are not significant for purposes of determining substantial equivalence.

Feature	Elecsys® IgE Test	Enzymun-Test® IgE.
Measurement approach	Electrochemiluminescence	Photometric
Instrument required	Boehringer Mannheim Elecsys automated immunoassay analyzer	Boehringer Mannheim ES 300/300 AL automated immunoassay analyzers
Reagent Formulation	Liquid; ready to use	Lyophilized; reconstitution required

Performance characteristics: The performance of the Elecsys® IgE Test is substantially equivalent to other products in commercial distribution intended for similar use. Most notably it is substantially equivalent to the currently marketed Enzymun-Test® IgE.

Feature	Elecsys® IgE Test	Enzymun-Test® IgE.
Precision	Within-Run %CV3.6% at 5.18 IU/mL2.1% at 105 IU/mL2.8% at 197 IU/mL3.2% at 398 IU/mL2.4% at 1010 IU/mLTotal %CV4.2% at 5.18 IU/mL1.9% at 105 IU/mL3.9% at 197 IU/mL3.9% at 398 IU/mL3.1% at 1010 IU/mL	Within-Run %CV2.1% at 102.7 IU/mL2.1% at 244.1 IU/mL2.8% at 375.4 IU/mLTotal %CV3.4% at 102.7 IU/mL3.4% at 244.1 IU/mL3.6% at 375.4 IU/mL
LowerDetectionLimit	0.10 IU/mL	1.44 IU/mL
MeasuringRange	0.10-4000 IU/ml	1.44-500 IU/ml

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510(k) Summary, Continued

Comparison to the predicate device (cont.)

Performance characteristics: continued

Feature	Elecsys® IgE Test	Enzymun-Test® IgE.
Specificity	No cross-reactivity with theimmunoglobulins G, A and M wasdetected.	No cross-reactions with IgG,IgA and IgM was detected.
Methodcomparison	Elecsys IgE vs Enzymun-Test IgEPassing/Babloky = -0.53 + 0.97xr = 1.0SD (md68) = 2.42N = 188Linear regressiony = -1.85 + 1.01xr = 1.0Sy.x = 5.86N = 188
Interferingsubstances:	No interference at:	No interference at:
BilirubinHemoglobinLipemiaBiotin	<37 mg/dL<1.1 g/dL<2200 mg/dL<100 ng/mL	<64.5 mg/dL<1 g/dL<1250 mg/dL<100 ng/mL

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8 1999 FEB

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Priscilla A. Hamill Regulatory Affairs Consultant Roche Diagnostics Corporation 9115 Hague Road P.O. Box 50457 Indianapolis, Indiana 46250-0457

Re: K984326 Trade Name: Elecsys IgE Test Regulatory Class: II Product Code: JHR Dated: December 2, 1998 Received: December 3, 1998

Dear Ms. Hamill:

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 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A 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 action. In addition, FDA may publish further announcements concerning your device in the Federal Register. 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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Page 2

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/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

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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510(k) Number (if known):

Device Name: Elecsys® IgE Test

Indications for Use: For in vitro quantitative determination of immunoglobulin E in human serum and plasma. The electrochemiluminescence inmunoassay "ECLIA" is intended for use on the Bochringer Mannheim Elecsys 1010 and 2010 immunoassay analyzers.

Determination of total serum IgE is useful as an aid in the diagnosis of allergic disease.

Rita E. Maisir

ision of Clinical Laboras

(PLEASE. DO NOT WRITE BEI.OW THIS LINE - CONTINUE ON ANOTHER PAGE IS NEEDED) .............................................................................................................................................................................. Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use V (Per 21 CFR 801.109)

Over-the-Counter Use

(Optional format 1-2-96)

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).