The Elecsys CMV IgG assay is an in vitro qualitative test for the detection of IgG antibodies to CMV in human serum, lithium-heparin plasma, K2-EDTA plasma, and K3-EDTA plasma. The test is intended as an aid in the determination of the serological status to CMV in individuals in which a CMV IgG test was ordered, including pregnant women.

Performance characteristics have not been evaluated in immunocompromised or immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at point of care facilities. This test is not intended for use in screening blood and plasma donors.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

Device Description

Elecsys CMV IgG is a two-step sandwich immunoassay with streptavidin microparticles, biotinylated recombinant CMV-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. The results are determined using a calibration curve which is instrument-specifically generated by a 2-point calibration and a master curve provided via the reagent bar code. Results greater than or equal to 1.0 U/mL are considered reactive CMV IgG antibody. The test system contains the human serum-based calibrators intended for use with the system.

Elecsys PreciControl CMV lgG contains liquid control serum. The controls are used for monitoring the accuracy of the Elecsys CMV IgG immunoassay.

Note: The reagent and calibrators are packaged together in the Elecsys CMV lgG assay kit, while the associated is packaged separately.

AI/ML Overview

Here's an analysis of the provided text regarding the Elecsys CMV IgG device, structured according to your requested information:

Elecsys CMV IgG Device Acceptance Criteria and Supporting Study

The provided 510(k) summary details the performance evaluation of the updated Elecsys CMV IgG assay.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state a quantitative "acceptance criteria" table with specific thresholds (e.g., "sensitivity ≥ X%", "specificity ≥ Y%"). Instead, it describes various studies conducted and concludes that "All performance specifications were met." and "The analytical studies demonstrate that the device is as safe, as effective, and performs as well as the legally marketed predicate device with improved biotin tolerance level up to 1200 ng/mL."

However, based on the studies described, we can infer performance aspects and reported outcomes:

Study Type	Implicit Acceptance Criteria/Goal	Reported Device Performance
Precision	Demonstrate acceptable repeatability and intermediate imprecision.	Repeatability and Intermediate imprecision were calculated according to CLSI EP05-A3. (No specific values provided, but stated that "All performance specifications were met.")
Biotin Interference	Achieve improved biotin tolerance; ensure no significant interference below a certain concentration.	Maximum value with no interference observed was 2400 ng/mL. The method sheet will be set to 1200 ng/mL. (Improvements from ≤ 100 ng/mL to ≤ 1200 ng/mL compared to the predicate.)
Method Comparison to Predicate	Demonstrate substantial equivalence between the updated assay and the predicate (K131605).	Positive Agreement and Negative Agreement were calculated. "The resulting data support the equivalence of the current non-biotin and biotin-updated assay." (No specific agreement percentages provided, but equivalence was concluded.)
Stability	Maintain performance over time under specified conditions.	"The stability data supports Roche Diagnostic's claims as reported in the package labeling." (No specific duration or performance metrics provided, but claims were supported.)

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

Precision Study:
- Sample Size: "3 levels of controls and 5 human serum samples per run, 2 runs per day for 21 days." This totals (3 controls + 5 samples) * 2 runs * 21 days = 336 individual measurements (or 21 days of testing on 8 distinct samples).
- Data Provenance: The text states "human serum samples" and "native human serum pools" for interference studies, implying human origin. No specific country of origin is mentioned. The studies are described as internal performance evaluations, which are typically prospective for the device under development.
Biotin Interference Study:
- Sample Size: "three serum samples (negative, positive close to cut-off, positive)" were used, each subjected to "11 dilution steps." This amounts to 3 samples * 11 dilutions = 33 individual sample preparations for testing.
- Data Provenance: "Native human serum pools" and "a single serum donor." No specific country of origin or retrospective/prospective nature is stated, but it's an analytical study, likely prospective.
Method Comparison to Predicate:
- Sample Size: "A total of 280 samples."
- Data Provenance: Not specified, but likely human serum/plasma samples. The study is analytical and likely prospective.

General Note on Data Provenance: For all studies, the document does not specify the country of origin of the data or explicitly state if the studies were retrospective or prospective, though the nature of these analytical performance studies suggests they were conducted prospectively as part of the device development and validation.

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

The device is an in vitro diagnostic (IVD) for the detection of IgG antibodies to CMV. The "ground truth" for such assays typically relies on established reference methods, a "gold standard" laboratory test result, or classification based on a patient's clinical status (e.g., infected vs. uninfected based on a battery of tests or clinical history).

The provided text does not mention the use of experts (like radiologists) to establish ground truth for any of the studies. For IVDs, "ground truth" is usually analytical (e.g., a sample spiked with a known concentration, or a sample with a confirmed status by a highly sensitive and specific reference method).

4. Adjudication Method for the Test Set

Since the studies described are analytical performance studies for an IVD, and not clinical studies involving interpretation by multiple human readers, there is no mention of an adjudication method like 2+1 or 3+1. Ground truth for these types of studies is typically established by the analytical reference method or preparation of known samples.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for imaging devices where human readers interpret results, sometimes with and without AI assistance, to assess the impact of AI on reader performance. The Elecsys CMV IgG is an automated immunoassay, not an imaging device requiring human interpretation of results in the same manner.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies described are essentially standalone performance evaluations of the device (Elecsys CMV IgG assay). As an automated immunoassay, the "algorithm" (the assay's chemical reactions and instrument's detection/calculation) provides a result directly. The studies like precision, biotin interference, and method comparison assess the performance of the assay itself without human intervention in the result determination process. The output is a quantitative (U/mL) or qualitative (reactive/non-reactive) result.

7. The Type of Ground Truth Used

The types of "ground truth" implicitly used in the analytical studies are:

Known Sample Status/Concentration: For the precision study, controls and samples with a certain expected concentration or qualitative status were used.
Known Biotin Concentration: For the biotin interference study, samples were "spiked with the interfering endogenous substance" (biotin) to known concentrations.
Predicate Device Results: For the method comparison study, the results from the legally marketed predicate device (Elecsys CMV IgG K131605) served as a comparative "ground truth" to demonstrate equivalence.

The document does not mention pathology, expert consensus, or outcomes data as ground truth, which are more common for diagnostic imaging or clinical decision support AI devices.

8. The Sample Size for the Training Set

The Elecsys CMV IgG assay is an immunoassay, not a machine learning or AI algorithm in the contemporary sense that requires a "training set" for model development. The assay relies on established biochemical reactions (electrochemiluminescence immunoassay "ECLIA"), calibration curves, and reagent lot-specific master curves. Therefore, there is no "training set" in the context of typical AI/ML algorithm development.

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

As there is no "training set" for an AI/ML algorithm, this question is not applicable to the Elecsys CMV IgG device as described. The assay's performance is driven by its chemical formulation, reagents, and instrument calibration, not by a learned model from a training dataset.

Summary

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October 12, 2022

Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Roche Diagnostics Bin Sun Regulatory Affairs Program Manager 9115 Hague Road Indianapolis, Indiana 46250

Re: K220911

Trade/Device Name: Elecsys CMV IgG Regulation Number: 21 CFR 866.3175 Regulation Name: Cytomegalovirus Serological Reagents Regulatory Class: Class II Product Code: LFZ Dated: March 28, 2022 Received: March 29, 2022

Dear Bin Sun:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 Part

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801and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Maria Garcia, Ph.D. Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

Submission Number (if known)

Device Name

Elecsys CMV IgG (09118551190)

Indications for Use (Describe)

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

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)

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510(k) Summary

Prepared on: 2022-03-28

Contact Details

21 CFR 807.92(a)(1)

Applicant Name	Roche Diagnostics
Applicant Address	9115 Hague Road Indianapolis IN 46250 United States
Applicant Contact Telephone	317-292-3781
Applicant Contact	Mr. Bin Sun
Applicant Contact Email	bin.sun.bs2@roche.com

21 CFR 807.92(a)(2)

Device Trade Name	Elecsys CMV IgG (09118551190)
Common Name	Cytomegalovirus serological reagents
Classification Name	Enzyme Linked Immunoabsorbent Assay, Cytomegalovirus
Regulation Number	866.3175
Product Code	LFZ

21 CFR 807.92(a)(3)
Legally Marketed Predicate Devices

Predicate #	Predicate Trade Name (Primary Predicate is listed first)	Product Code
K131605	Elecsys CMV IgG Immunoassay	LFZ

21 CFR 807.92(a)(4)
Device Description SummaryElecsys CMV IgG is a two-step sandwich immunoassay with streptavidin microparticles, biotinylated recombinant CMV-specific antigen labeled with a ruthenium complex and electrochemiluminescence detection. The results are determined using a calibration curve which is instrument-specifically generated by a 2-point calibration and a master curve provided via the reagent bar code. Results greater than or equal to 1.0 U/mL are considered reactive CMV IgG antibody. The test system contains the human serum-based calibrators intended for use with the system.

Elecsys PreciControl CMV lgG contains liquid control serum. The controls are used for monitoring the accuracy of the Elecsys CMV IgG immunoassay.

Note: The reagent and calibrators are packaged together in the Elecsys CMV lgG assay kit, while the associated is packaged separately.

Intended Use/Indications for Use

Performance characteristics have not been evaluated in immunosuppressed individuals. This test is not intended for use in neonatal screening or for use at point of care facilities. This test is not intended for use in screening blood and plasma donors.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

Indications for Use Comparison

21 CFR 807.92(a)(5)

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Elecsys CMV IgG (updated assay, Mat. No. 09118551190) is substantially equivalent to Elecsys CMV IgG, cleared under K131605.

The intended use of Elecsys CMV IgG was updated to remove analyzers that are no longer supported for use with Roche assays. The indications for use of updated Elecsys CMV IgG assay did not change from the predicate device.

Technological Comparison

21 CFR 807.92(a)(6)

Roche Diagnostics has updated the current Elecsys CMV IgG assay in order to improve the biotin tolerance from ≤ 100 ng/mL to ≤ 1200 ng/mL and to reduce streptavidin interference. A technical solution was implemented by adding an of the reagents, which allows depletion of bioting free bioting free bioting a streptavidin interference reducing agent to enhance the streptavidin tolerance. No other technological characteristics were changed. The information submitted in this Premarket Notification supports a substantial equivalent decision.

Non-Clinical and/or Clinical Tests Summary & Conclusions 21 CFR 807.92(b)

1. Precision

The precision of the Elecsys CMV IgG assay was evaluated on one cobas e 801 immunoassay analyzer with one reagent lot. The protocol consisted of testing 2 aliquots of each of three levels of controls and 5 human serum samples per run, 2 runs per day for 21 days. The samples were run in randomized order on the analyzer. Repeatability and Intermediate imprecision were calculated according to CLSI EP05-A3 including the 95% confidence interval.

2. Biotin Interference

The effect on quantitation of analyte in the presence of biotin using the updated Elecsys CMV IgG assay was determined using three serum samples (negative, positive close to cut-off, positive) according to CLSI EP07-A3 Appendix A.

Native human serum pools were used for the low and mid concentration samples. The high human serum sample comprises a single serum donor. Samples were divided, and one part of each sample was spiked with the interfering endogenous substance and used as the "interference pool." Another part of the same volume of solvent as the interfering endogenous substance (without interfering substance) and used as the related "dilution pool."

A series of 11 dilution steps were prepared by mixing the interference pools and the related dilution pools.

The mean recovery (absolute deviation or percent recovery) was calculated for each sample compared to the expected value. The maximum value with no interference observed was 2400 ng/mL. The method sheet will be set to 1200 ng/mL.

3. Method Comparison to Predicate

A method comparison study was performed to demonstrate equivalency between the current Elecsys CMV IgG assay and the biotin-updated Elecsys CMV IgG assay on one cobas e 801 analyzer.

A total of 280 samples were measured with one reagent lot of the current Elecsys CMV IgG assay and three different reagent lots of the biotin-updated Elecsys CMV IgG assay in single determination on the cobas e 801 analyzer. Results are presented in a 3x3 table. Positive Agreement and Negative Agreement between the current and updated assay were calculated. The resulting data support the equivalence of the current non-biotin and biotin-updated assay.

4. Stability

The stability studies and acceptance criteria have been reviewed and found to be acceptable. The stability data supports Roche Diagnostic's claims as reported in the package labeling.

All performance specifications were met. The infornation provided in this 510(k) Premarket Notification is complete and supports a substantial equivalence decision. The analytical studies demonstrate that the device is as safe, as effective, and performs as well as the legally marketed predicate device with improved biotin tolerance level up to 1200 ng/mL.

Not Applicable

Regulation Number and Section

§ 866.3175 Cytomegalovirus serological reagents.

(a)
Identification. Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.(b)
Classification. Class II (performance standards).