The LIAISON® EA IgG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer family* for the qualitative determination of specific IgG antibodies to Epstein-Barr virus (EBV) early antigen-diffuse [EA(D)] in human serum. This assay uses a 47-kDa recombinant antigen expressed in E. coli DH-1 cells. When performed in conjunction with other EBV markers, this assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr Viral Syndrome in patients with signs and symptoms of EBV infectious mononucleosis.

The DiaSorin LIAISON® EA IgG Serum Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® EA IgG assay on the LIAISON® Analyzer family*. The performance characteristics of the LIAISON® EA IgG controls have not been established for any other assay or instrument platforms different from the LIAISON® and LIAISON® XL.

*(LIAISON® and LIAISON® XL)

Device Description

The LIAISON® EA IgG is an indirect chemiluminescence immunassay (CLIA) technology on the LIAISON Analyzer family* for the qualitative determination of IgG antibodies to Epstine-Barr virus (EBV) early antigen-diffuse [ea(D)] in human serum.

The LIAISON® EA IgG Serum Control Set (negative and positive) consists of liquid ready-to-use controls in human serum/defibrinated plasma. The negative control is intended to provide an assay response characteristic of negative patient specimens and the positive control is intended to provide an assay response characteristic of positive patient specimens.

The controls are designed for use with DiaSorin LIAISON® EA IgG assay on the LIAISON® Analyzer family.

AI/ML Overview

The provided document is a 510(k) summary for a medical device called LIAISON® EA IgG and LIAISON® EA IgG Serum Control Set. It details the device's characteristics, intended use, and a comparison to a predicate device, focusing on modifications made to the control set. The information necessary to fully address all parts of your request, particularly those related to detailed study methodologies, expert qualifications, and specific numerical acceptance criteria/results for diagnostic accuracy (like sensitivity/specificity or AUROC), is not present in this 510(k) summary. This document primarily focuses on demonstrating substantial equivalence through performance characteristics of the controls and proving that changes do not introduce new risks to the assay's performance, rather than a full diagnostic accuracy study of the assay itself.

However, I can extract and infer the following:

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

The document states that "Non-clinical verification and validation testing conducted with the LIAISON® EA IgG and LIAISON® EA IgG Serum Control Set demonstrate that the modified device meets predetermined acceptance criteria". While the specific numerical acceptance criteria are not explicitly detailed (e.g., a specific percentage for precision or commutability), the types of performance evaluated and confirmed are listed.

Performance Characteristic Tested (Acceptance Criteria Mentioned but not quantified)	Reported Device Performance
Commutability between samples and controls (matrix effect)	Modified device meets "predetermined acceptance criteria" for commutability between samples and controls.
Precision equivalence between samples and controls (20 Day Precision)	Modified device meets "predetermined acceptance criteria" for precision equivalence between samples and controls.
Control value assignment	Modified device meets "predetermined acceptance criteria" for control value assignment.
Control range definition	Modified device meets "predetermined acceptance criteria" for control range definition.
Shelf-life stability (12 months at 2-8°C)	Real Time Stability testing supports a shelf-life of 12 months at 2-8°C.
Open Use Stability (8 weeks at 2-8°C between uses)	Real Time Stability testing supports 8 weeks open use stability when stored at 2-8°C between uses. (This is an improvement from the predicate's 4 weeks).

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

The document does not provide details on the specific sample sizes used for the "test set" in terms of number of patient samples. The studies mentioned ("Commutability," "Precision equivalence," "Control value assignment," "Control range definition," and "Real Time Stability") relate to the performance of the controls and the assay system with these controls. Information regarding data provenance (country, retrospective/prospective) for these specific validation studies is also not provided.

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 applicable and not provided in the context of this 510(k) summary. The document pertains to a serological assay (LIAISON® EA IgG) and its controls, not an AI or imaging device that uses expert-established ground truth for a test set in the traditional sense of diagnostic accuracy studies. The "ground truth" for a serological assay would typically be established through other laboratory methods, clinical diagnosis, or a composite reference standard, rather than expert interpretation of images or other data that requires such qualifications.

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

This information is not applicable and not provided. See point 3.

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 an AI-assisted device and therefore no MRMC study or AI-related effectiveness study was conducted or reported.

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

This is not an AI algorithm. It is a serological immunoassay kit and its controls.

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

For the LIAISON® EA IgG assay itself (not the controls), the "ground truth" for its intended use is defined by its ability to detect specific IgG antibodies to EBV early antigen-diffuse [EA(D)]. This is a biochemical "truth" established by the immunological reaction in the assay. The assay is intended to be used "in conjunction with other EBV markers" as an aid in clinical laboratory diagnosis of Epstein-Barr Viral Syndrome in patients with signs and symptoms of EBV infectious mononucleosis. Therefore, the ultimate clinical ground truth for the disease diagnosis would involve a combination of various EBV markers and clinical symptoms/outcomes, but the "ground truth" for the device's performance itself is its accuracy in detecting the target antibody. The document does not provide details on how the original assay (K060204) was validated against clinical ground truth or other reference methods in terms of sensitivity and specificity for disease diagnosis. This 510(k) is specifically for modifications to the controls and showing they do not negatively impact the previously cleared assay.

8. The sample size for the training set

This is not an AI algorithm. The concept of a "training set" in the machine learning sense does not apply here. The "training" for such an assay involves method development and optimization using various reagent lots, antigen sources, and panels of known positive/negative samples, but these are not quantified in terms of a "training set" like in AI.

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

Not applicable as described for AI (see point 8). For the development of the assay, the "ground truth" for calibrators and controls would be established through careful characterization using reference methods, purified antigens/antibodies, and panels of clinically characterized patient samples (e.g., samples from confirmed EBV infections and healthy individuals), but specific details are not provided in this summary.

Summary

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

January 04, 2017

DIASORIN INCORPORATED JOHN C. WALTER PRESIDENT 1951 NORTHWESTERN AVE. STILLWATER, MN 55082

Re: K162959

Trade/Device Name: LIAISON® EA IgG and LIAISON® EA IgG Serum Control Set Regulation Number: 21 CFR 866.3235 Regulation Name: Epstein-Barr virus serological reagents Regulatory Class: Class I Product Code: LSE, JJX Dated: October 21, 2016 Received: December 5, 2016

Dear Mr. Walter:

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 as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the

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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 yours, Kristian M. Roth -S 2017.01.04 10:57:01 -05'00'

For: Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology 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) K162959

Device Name LIAISON® EA IgG LIAISON® EA IgG Serum Control Set

Indications for Use (Describe)

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

*(LIAISON® and LIAISON® XL)

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.

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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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DiaSorin LIAISON® EA IgG and LIAISON® EA IgG Serum Control Set Special 510(k): Device Modification

510(k) SUMMARY

SUBMITTED BY:	DiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285
CONTACT:	Sunita TeekasinghRegulatory Affairs ManagerEmail: sunita.teekasingh@diasorin.com
DATE OF PREPARATION:	October 21, 2016
NAME OF DEVICE:
Trade Name:	LIAISON® EA IgGLIAISON® EA IgG Serum Control Set
Common Names/Description:	Immunoassay for the detection of IgG antibodies toEBV early antigen-diffuse [EA(D)]
Classification:	Epstein-Barr virus serological reagents, 21 CFR866.3235; Class I, Microbiology (83)
Product Code:	LSE, JJX
PREDICATE DEVICE:	DiaSorin LIAISON® EA IgG (K060204)

DEVICE DESCRIPTION:

The controls are designed for use with DiaSorin LIAISON® EA IgG assay on the LIAISON® Analyzer family.

INTENDED USE:

The LIAISON EA IgG assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer family* for the qualitative determination of specific IgG antibodies to Epstein-Barr virus (EBV) early antigen-diffuse [EA(D)] in human serum. This assay uses a 47-kDa recombinant antigen expressed in E. coli DH-1 cells. When performed in conjunction with other EBV markers, this assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr Viral Syndrome in patients with signs and symptoms of EBV infection such as infectiousmononucleosis.

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LIAISON®EA IgG Serum Control Set:

*(LIAISON® and LIAISON® XL)

COMPARISON TO THE PREDICATE (Description of the Modifications to the Legally Marketed Device):

The following tables provide a summary of the FDA cleared LIAISON® EA IgG assay.

LIAISON® EA IgG assay
Characteristic	Predicate DeviceDiaSorin LIAISON® EA IgGK060204, Cleared 10/18/2006	DiaSorin LIAISON® EA IgG
IntendedUse/Indications forUse	The LIAISON® EA IgG assay useschemiluminescent immunoassay (CLIA)technology on the LIAISON® Analyzerfamily* for the qualitative determination ofspecific IgG antibodies to Epstein-Barrvirus (EBV) early antigen-diffuse [EA(D)]in human serum. This assay uses a 47-kDa recombinant antigen expressed in E.Coli DH-1 cells. When performed inconjunction with other EBV markers, thisassay can be used as an aid in theclinical laboratory diagnosis of Epstein-Barr Viral Syndrome in patients with signsand symptoms of EBV infection such asinfectious mononucleosis.*(LIAISON® and LIAISON® XL)	No Change
Technology/Assay Principle	Chemiluminescent Immunoassay (CLIA)	No Change
SampleHandling/AssayProcessing	Automated	No Change
Storage	Store at 2-8° C until ready to use	No Change
Measured Analyte	IgG antibodies to Epstein-Barr virus (EBV)early antigen-diffuse [EA(D)].	No Change
Assay PerformanceCharacteristics	No Change	No Change
Labeling (IFU)	References buffer based controls	References serum basedcontrols
Controls	Provided Separately	No Change

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Changes to the DiaSorin LIAISON® EA IgG Serum Control Set include a 100% serum/defibrinated plasma based matrix and the extension of the open use stability claim.

The following table provides a summary of the similarities and differences between the FDA cleared LIAISON® Control EA IgG Control and the modified device, LIAISON® EA IgG Serum Control Set.

Summary of Similarities and Differences LIAISON® EA IgG Serum Control Set
Characteristic	Predicate DeviceDiaSorin LIAISON® Control EA IgGK060204, Cleared 10/18/2006	Modified DeviceDiaSorin LIAISON® EA IgG SerumControl Set
Intended Use	The LIAISON® EA IgG Controls(negative, positive) are used formonitoring substantial reagent failureof the LIAISON® EA IgGchemiluminescent immunoassay(CLIA). The LIAISON® EA IgGquality control material contains onlya 5% serum matrix and may notadequately control the DiaSorinLIAISON® EA IgG assay for serumspecimens. The performance of theLIAISON® EA IgG Controls has notbeen established with any other EAassay or instrument platformsdifferent from LIAISON® andLIAISON® XL.	The DiaSorin LIAISON® EA IgGSerum Control Set is intended foruse as assayed quality controlsamples to monitor the performanceof the LIAISON® EA IgG assay onthe LIAISON® Analyzer family. Theperformance characteristics of theLIAISON® EA IgG controls have notbeen established for any other assayor instrument platforms different fromthe LIAISON® and LIAISON® XL.(LIAISON® and LIAISON® XL)
Negative Control	5% Human serum/defibrinatedplasma not reactive for EA IgGantibodies, diluted in PBS buffer,BSA, with ProClin® 300 as apreservative.	Human serum/defibrinated plasmanon-reactive for EA IgG antibodies,0.1% ProClin® 300 and 0.09%sodium azide.
Positive Control	5% Human serum/defibrinatedplasma reactive for EA IgGantibodies, diluted in PBS buffer,BSA, with ProClin® 300 as apreservative and an inert yellow dye.	Human serum/defibrinated plasmareactive for EA IgG antibodies, 0.1%ProClin® 300 and 0.09% sodiumazide.
ReagentConfiguration	2 vials each level (negative andpositive) 0.7 mL/vial, ready to use.	Same
Storage	Store at 2-8°C	Same
Open UseStability	Once opened controls are stable forfour (4) weeks when properly storedat 2-8°C between uses.	Once opened controls are stable foreight (8) weeks when properly storedat 2-8°C between uses.

ProClin® is a trademark of the Dow Chemical Company (Dow) or an affiliated company.

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SUMMARY OF PERFORMANCE DATA:

Non-clinical verification and validation testing conducted with the LIAISON® EA IgG and LIAISON® EA IgG Serum Control Set demonstrate that the modified device meets predetermined acceptance criteria, supporting equivalency of the modified device to the cleared device. Evidence is demonstrated through the following studies:

Testing of the LIAISON® EA IgG Serum Control Set to validate and verify:

Commutability between samples and controls (matrix effect)
- Precison equivalence between samples and controls
  - o 20 Day Precison
Control value assignment
Control range definition

Real Time Stability testing conducted on the LIAISON® EA IgG Serum Control Set to support the following product claims:

. Shelf-life of 12 months at (2-8°C)
Eight (8) weeks open use stability when stored at 2-8°C between uses ●

Based on the results from the validation and verification activities, the modifications to the LIAISON® EA IgG Serum Control Set do not introduce any new risks to the performance of the device.

CONCLUSION:

As summarized, the LIAISON® EA IgG and LIAISON® EA IgG Serum Control Set is substantially equivalent to the originally cleared device. The device do not constitute new intended/indications for use, or changes to the fundamental scientific technology. Performance testing of the device demonstrates that the device functions as intended, meeting the requirements of design specifications. The device was determined to be substantially equivalent to the previously cleared device.

The material submitted in this Special 510(k) is complete and supports a substantial equivalence decision. The labeling satisfies the requirements of 21 CFR 809.10.

Regulation Number and Section

§ 866.3235 Epstein-Barr virus serological reagents.

(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).