ImmunoCAP Specific IgE is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum or plasma (EDTA or Na-Heparin). ImmunoCAP Specific IgE is to be used with instruments Phadia 100, Phadia 1000, Phadia 2500 and Phadia 5000. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories.

ImmunoCAP Total IgE is an in vitro test system for the quantitative measurement of circulating total IgE in human serum and plasma. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories. ImmunoCAP Total IgE is to be used with the instruments Phadia 100, Phadia 250, Phadia 1000, Phadia 2500 or Phadia 5000.

Device Description

The general ImmunoCAP reagents include ImmunoCAP Specific or Total IgE Conjugate, ImmunoCAP Specific or Total IgE Curve Control, ImmunoCAP Specific or Total IgE Calibrators, Specific or Total IgE anti-IgE, Allergen ImmunoCAP carriers (only for determination of Specific IgE), Development solution, Stop Solution and Washing Solution. The method specific reagents consist of individual purified allergen (native or recombinant), covalently coupled to a support in a plastic housing (only for determination of Specific IgE).

Phadia 100, Phadia 250, Phadia 2500 and Phadia 5000 instruments with associated software process all steps of the assay and calculate results automatically after the assay is completed.

AI/ML Overview

The document describes the ImmunoCAP Specific IgE Assay and ImmunoCAP Total IgE Assay, which are in vitro quantitative assays for measuring allergen-specific and total IgE in human serum or plasma. The primary purpose of this 510(k) submission is to introduce a new Reference Material for the standardization of these assays.

Here's an analysis of the provided information concerning acceptance criteria and the study that proves the device meets them:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly list a table of acceptance criteria with corresponding device performance for the ImmunoCAP Specific IgE Assay and ImmunoCAP Total IgE Assay. The submission is focused on a change in the reference material and proving substantial equivalence to previously cleared devices.

However, the "Conclusion" section (page 6) states: "The safety and effectiveness of the cleared ImmunoCAP Specific and Total IgE systems, intended for the determination of specific and total IgE antibodies, have been established in previous 510(k) submissions. The Reference Material change does not affect the Intended Use or the Indications for Use statements, the fundamental scientific technology, specifications or manufacturing methods of the assays. The verification studies performed demonstrate that the updated ImmunoCAP Specific and Total IgE assays are substantially equivalent to the currently cleared products."

This implies that the acceptance criteria for these assays were established and met in prior 510(k) submissions, and the current submission aims to demonstrate that changing the reference material does not negatively impact the performance against those pre-established criteria. The specific performance metrics themselves (e.g., precision, accuracy, linearity) are not detailed in this document for the current change.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

The document mentions two studies conducted to evaluate the impact of the new reference material:

"Concentration determination of two stock solutions used for production of ImmunoCAP Specific IgE Calibrators"
"Evaluation of clinical negative and positive patient samples in ImmunoCAP Specific IgE"

Sample Size: The exact sample sizes for these studies are not provided in this document.
Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not provided in the document. The studies involve laboratory-based comparisons of calibration and patient samples, rather than subjective interpretation by experts. The "ground truth" here would relate to the accurate measurement of IgE concentration, which is assessed through reference materials and comparative analysis with previously established methods, not expert consensus in the same way it would be for imaging diagnostics.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not applicable and therefore not provided in the document. Adjudication methods like 2+1 or 3+1 are typically used in clinical trials where multiple human readers or experts are involved in interpreting results which are then subject to a consensus process. The studies described are laboratory-based assays comparing different versions of a product.

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

An MRMC comparative effectiveness study was not performed. This type of study is relevant for imaging diagnostics or other AI-assisted diagnostic tools where human interpretation is a key component. The ImmunoCAP assays are in vitro diagnostic tests that produce quantitative results, not interpretations by human readers.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

The ImmunoCAP assays are inherently "standalone" in the sense that they are laboratory tests that generate quantitative results automatically using instruments (Phadia 100, 1000, 2500, 5000) and associated software after the assay procedure. There isn't a human-in-the-loop performance component in the measurement itself, though clinical interpretation of the quantitative results by a healthcare professional is part of their intended use. The performance characteristics would be assessed based on the accuracy and precision of the system's measurements. The document implies laboratory "verification studies" were performed to compare the new device to the predicate.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for the ImmunoCAP assays, as indicated by the "Description of change" (page 6), is linked to international standards for serum IgE. Specifically, the new Reference Material is traceable to the 3rd WHO International Standard (300 WHO IRR) for serum IgE (11/234), replacing the 2nd WHO IRR. This means the accuracy of the device's measurements is evaluated against these established international biological reference standards.

8. The sample size for the training set

This information is not provided in the document. For in vitro diagnostic assays, "training set" is not a standard term in the same way it is for machine learning algorithms. The development and calibration of such assays typically involve optimizing reagents and protocols using a range of known standards and samples, but these are not explicitly referred to as "training sets."

9. How the ground truth for the training set was established

As noted in point 8, the concept of a "training set" with established ground truth is not explicitly addressed in the document in the context of algorithm development. However, the calibration and standardization of the ImmunoCAP assays rely on established WHO International Standards for serum IgE. These standards themselves are developed through extensive collaborative studies involving numerous laboratories and experts to assign specific IgE concentration units, thereby serving as the "ground truth" reference for calibration and measurement accuracy.

Summary

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Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 28, 2016

PHADIA AB MARTIN MANN REGULATORY AFFAIRS MANAGER 4169 COMMERCIAL AVENUE PORTAGE, MI 49002

Re: K161889

Trade/Device Name: ImmunoCAP Specific IgE Assay and ImmunoCAP Total IgE Assay Regulation Number: 21 CFR 866.5750 Regulation Name: Radioallergosorbent (RAST) immunological test system Regulatory Class: Class II Product Code DHB, DGC Dated: July 8, 2016 Received: July 11, 2016

Dear Mr. Mann:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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]); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements

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as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

Kelly Oliner -S

For.

Leonthena Carrington, MS, MBA, MT(ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

Device Name ImmunoCAP Specific IgE

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

	Prescription Use (Part 21 CFR 801 Subpart D)
	Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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Indications for Use

510(k) Number (if known)

Device Name ImmunoCAP Total IgE

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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Special 510(k) Submission, Reference Material Change for ImmunoCAP Total IgE and ImmunoCAP Specific IgE Assays A.7 510k Summary

510(k) Summary

This summary of safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR Part 807.92.

Premarket Notification 510(k) No:

Date of Summary Preparation:	July 7, 2016
Manufacturer:	Phadia ABRapsgatan 7PP.O. Box 6460751 37 Uppsala, Sweden
US Distributor:	Phadia US Inc.4169 Commercial AvenuePortage, MI 49002
Company contact person:	Martin MannRegulatory Affairs ManagerPhadia US Inc.269-492-1957martin.mann@thermofisher.com

Device Name (1):

ImmunoCAP Specific IgE

Common Name:

Automated in vitro quantitative assay for the measurement of allergen specific IgE antibodies.

Classification:Product CodeClassCFR	DHB
	II
	866.5750
Substantial Equivalence to:ImmunoCAP Specific IgE	K051218

Indications For Use / Intended Use Statement

ImmunoCAP Specific IgE is an in vitro quantitative assay for the measurement of allergen specific lgE in human serum or plasma (EDTA or Na-Heparin). ImmunoCAP Specific IgE is to be used with instruments Phadia 100, Phadia 1000, Phadia 2500 and Phadia 5000. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories.

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Special 510(k) Submission, Reference Material Change for ImmunoCAP Total IgE and ImmunoCAP Specific IgE Assays A.7 510k Summarv

Device Name (2): ImmunoCAP Total IgE

Common name:

Automated in vitro quantitative assay for the measurement of Total IgE

Classification:
Product code	DGC
Class	II
CFR	866.5510
Substantial Equivalence to:	K133404
ImmunoCAP Total IgE

Indications For Use / Intended Use Statement

ImmunoCAP Total IgE is an in vitro test system for the quantitative measurement of circulating total lgE in human serum and plasma. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories. ImmunoCAP Total IgE is to be used with the instruments Phadia 100, Phadia 250, Phadia 1000, Phadia 2500 or Phadia 5000.

Device Description

Assav reagents

Instrument System

Phadia 100, Phadia 250, Phadia 2500 and Phadia 5000 instruments with associated software process all steps of the assay and calculate results automatically after the assay is completed.

ImmunoCAP Specific IgE, Test Principle

The allergen of interest, covalently coupled to ImmunoCAP, reacts with the specific IgE in the patient sample. After washing away non-specific IgE, enzyme labeled antibodies against IgE are added to form a complex. After incubation, unbound enzyme-anti-IgE is washed away and the bound complex is then incubated with a developing agent. After stopping the reaction, the fluorescence of the eluate is measured. The higher the response value, the more specific IgE is present in the specimen. To evaluate the test results, the responses for the patient samples are transformed to concentrations with the use of a calibration curve.

lmmunoCAP Total IgE, Test Principle

Anti-IgE covalently coupled to ImmunoCAP, reacts with the total IgE in the patient sample. After washing, enzyme labeled antibodies against IgE are added to form a complex. Following

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Special 510(k) Submission, Reference Material Change for ImmunoCAP Total IgE and ImmunoCAP Specific IgE Assays A.7 510k Summarv

incubation, unbound enzyme-anti IgE is washed away and the bound complex is then incubated with a developing agent. After stopping the reaction, the fluorescence of the eluate is measured. The higher the response value, the more IgE is present in the sample. To evaluate the test results, the responses for the patient samples are transformed to concentrations with the use of a calibration curve.

Description of change

Introduction of a new Reference Material for standardization of ImmunoCAP Specific and Total IgE assays, the 3th WHO International Standard (300 WHO IRR) for serum IgE (11/234). No change of Intended Use/Indications for Use or fundamental scientific technology of the assay system has been made. No change of specifications or manufacturing methods for any assay reagents has been made.

Directions for Use for ImmunoCAP Specific and ImmunoCAP Total IgE will be updated to reflect the change. The update will be phased in over time. During a transition period Phadia intends to supply an intermediate version of labelling containing traceability information to either the old and new reference material.

Performance characteristics

The New Device, IgE calibrators traceable to 30 WHO IRR was compared with the Predicate Device, IgE calibrators traceable to 2nd WHO IRR, in two separate studies:

Concentration determination of two stock solutions used for production of ImmunoCAP ● Specific IgE Calibrators
. Evaluation of clinical negative and positive patient samples in ImmunoCAP Specific IgE

Conclusion

The safety and effectiveness of the cleared ImmunoCAP Specific and Total IgE systems, intended for the determination of specific and total IgE antibodies, have been established in previous 510(k) submissions. The Reference Material change does not affect the Intended Use or the Indications for Use statements, the fundamental scientific technology, specifications or manufacturing methods of the assays. The verification studies performed demonstrate that the updated ImmunoCAP Specific and Total IgE assays are substantially equivalent to the currently cleared products.

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).