Elecsys AFP

K220176 · Roche Diagnostics · LOJ · Sep 15, 2022 · Immunology

Device Facts

• Record ID: K220176
• Device Name: Elecsys AFP
• Applicant: Roche Diagnostics
• Product Code: LOJ · Immunology
• Decision Date: Sep 15, 2022
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.6010
• Device Class: Class 2

Intended Use

Immunoassay for the in vitro quantitative determination of α1-fetoprotein in human serum and plasma to aid in the management of patients with non-seminomatous germ cell tumors. The electrochemiluminescence immunoassay “ECLIA” is intended for use on the cobas e immunoassay analyzers.

Device Story

Elecsys AFP is an in vitro diagnostic immunoassay for quantitative determination of alpha-fetoprotein (AFP) in human serum and plasma. Used on cobas e immunoassay analyzers in clinical laboratory settings. Operates via electrochemiluminescence immunoassay (ECLIA) sandwich principle; 18-minute duration. Input: 10 uL sample, biotinylated monoclonal AFP antibody, and ruthenium-labeled monoclonal AFP antibody. Complex binds to streptavidin-coated microparticles; magnetically captured on electrode surface. Voltage application induces chemiluminescent emission measured by photomultiplier. Results calculated via instrument-specific calibration curve. Updated version includes anti-biotin antibody to deplete free biotin and streptavidin interference reducing agent to improve tolerance. Output provides quantitative AFP levels to assist clinicians in monitoring non-seminomatous germ cell tumor management.

Clinical Evidence

No new clinical studies were performed. Substantial equivalence is supported by analytical performance data including precision (within-lab CV 3.4-4.2%, total CV 3.5-9.1%), linearity (R²=0.958), and method comparison against the predicate (Passing-Bablok regression slope 0.965-0.971, Pearson r ≥ 0.999). Interference testing confirmed no significant biotin interference up to 1200 ng/mL.

Technological Characteristics

Quantitative sandwich ECLIA. Reagents: streptavidin-coated microparticles, biotinylated monoclonal anti-AFP antibodies, ruthenium-labeled monoclonal anti-AFP antibodies. Energy source: electrical stimulation of chemiluminescence. Platform: cobas e 601 analyzer. Measuring range: 1.5–1000 IU/mL. Traceable to 1st IRP WHO Reference Standard 72/225.

Indications for Use

Indicated for the management of patients with non-seminomatous germ cell tumors. For use with human serum and plasma samples.

Regulatory Classification

Identification

A tumor-associated antigen immunological test system is a device that consists of reagents used to qualitatively or quantitatively measure, by immunochemical techniques, tumor-associated antigens in serum, plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease.

Special Controls

*Classification.* Class II (special controls). Tumor markers must comply with the following special controls: (1) A guidance document entitled “Guidance Document for the Submission of Tumor Associated Antigen Premarket Notifications (510(k)s) to FDA,” and (2) voluntary assay performance standards issued by the National Committee on Clinical Laboratory Standards.

Predicate Devices

• Elecsys AFP (K981282)

Submission Summary (Full Text)

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September 15, 2022

Roche Diagnostics Jamie Ferguson Regulatory Affairs Principal 9115 Hague Road Indianapolis, Indiana 46250

Re: K220176

Trade/Device Name: Elecsys AFP Regulation Number: 21 CFR 866.6010 Regulation Name: Tumor-Associated Antigen Immunological Test System Regulatory Class: Class II Product Code: LOJ Dated: January 20, 2022 Received: January 21, 2022

Dear Jamie Ferguson:

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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and 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 (OS) 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 ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known) K220176

Device Name Elecsys AFP

Indications for Use (Describe)

Immunoassay for the in vitro quantitative determination of c1-fetoprotein in human serum and in the management of patients with non-seminomatous germ cell tumors.

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

| Type of Use (Select one or both, as applicable) |
|-------------------------------------------------|
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| <div> <span> </span> Prescription Use (Part 21 CFR 801 Subpart D) </div> |
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| <div> <span> </span> Over-The-Counter Use (21 CFR 801 Subpart C) </div> |

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# Elecsys AFP 510(k) Summary

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of 21 CFR 807.92.

In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).

| Submitter Name | Roche Diagnostics |
|--------------------------------------|-------------------------------------------------------------------------------------|
| Address | 9115 Hague Road<br>P.O. Box 50416<br>Indianapolis, IN 46250-0457 |
| Contact | Contact: Jamie Ferguson<br>Phone: [phone]<br>Email: [e-mail] |
| Date Prepared | September 15, 2022 |
| Proprietary Name | Elecsys AFP |
| Common Name | Tumor-associated antigen immunological test system |
| Classification Name | Kit, Test, Alpha-Fetoprotein for Testicular Cancer |
| Product Codes,<br>Regulation Numbers | LOJ, 21 CFR 866.6010 |
| Predicate Devices | K981282, Elecsys AFP |

The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the Elecsys AFP.

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#### 1. DEVICE DESCRIPTION SUMMARY

Immunoassay for the in vitro quantitative determination of αι-fetoprotein in human serum and plasma to aid in the management of patients with non-seminomatous germ cell tumors.

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

Elecsys AFP utilizes a sandwich test principle and has a total test duration of 18 minutes.

- 1st incubation: 10 uL of sample, a biotinylated monoclonal AFP specific antibody, and . a monoclonal AFP specific antibody labeled with a ruthenium complex® react to form a sandwich complex.
- 2nd incubation: After addition of streptavidin-coated microparticles, the complex . becomes bound to the solid phase via interaction of biotin and streptavidin.
- The reaction mixture is aspirated into the measuring cell where the microparticles are . magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell/ProCell M. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier.
- Results are determined via a calibration curve which is instrument-specifically . generated by 2 point calibration and a master curve provided via the reagent barcode or e barcode.
- a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy) )

The reagent rackpack (M, R1, R2) is labeled as AFP:

- M: Streptavidin-coated microparticles (transparent cap), 1 bottle. 12 mL: Streptavidin-. coated microparticles 0.72 mg/mL; preservative.
- R1: Anti-AFP-Ab~biotin (gray cap), 1 bottle, 17 mL: Biotinylated monoclonal anti-. AFP antibodies (mouse) 4.5 mg/L; phosphate buffer 100 mmol/L, pH 6.0; preservative.

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- R2: Anti-AFP-Ab~Ru(bpy) (black cap), 1 bottle, 17 mL: Monoclonal anti-AFP . antibodies (mouse) labeled with ruthenium complex 12.0 mg/L; phosphate buffer 100 mmol/L, pH 6.0; preservative.
#### INTENDED USE/INDICATIONS FOR USE 2.

Immunoassay for the in vitro quantitative determination of a1-fetoprotein in human serum and plasma to aid in the management of patients with non-seminomatous germ cell tumors.

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

#### INDICATIONS FOR USE COMPARISON 3.

Elecsys AFP (updated assay, Mat. No. 09015086160) is substantially equivalent to Elecsys AFP, cleared under K981282.

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

#### TECHNOLOGICAL COMPARISON 4.

Roche Diagnostics has updated the current Elecsys AFP assay in order to improve the biotin tolerance from ≤ 60 ng/mL to ≤ 1200 ng/mL and to reduce streptavidin interference. A technical solution was implemented by adding an anti-biotin antibody to one of the reagents, which allows depletion of biotin in patient samples by binding free biotin, and by adding 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 5.

Precision measurements were conducted for both 21 days and 5 days with the Elecsys AFP assay to evaluate repeatability (within-run precision) and intermediate precision (within-laboratory

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precision) according the CLSI guideline EP05-A3. All predefined acceptance criteria was met for the precision experiments.

Lot-to-lot reproducibility was performed for the Elecsys AFP assay using three reagent lots. All predefined acceptance criteria was met for the lot-to-lot reproducibility experiment.

The Limit of Blank (LoB) was determined according to CLSI EP17-A2. The LoB claim in the labeling will be set to 0.75 IU/mL.

The Limit of Detection (LoD) was determined according to CLSI EP17-A2. The LoD claim in the labeling will be set to 1.5 IU/mL.

The Limit of Quantitation (LoQ) was determined according to CLSI EP17-A2. The LoQ claim in the labeling will be set to 1.5 IU/mL.

Linearity was evaluated according to CLSI EP06-A with the Elecsys AFP assay on one cobas e 601 analyzer. Linearity was confirmed in the range of 0.58 IU/mL - 1129 IU/mL, and a measuring range of 1.50-1000 IU/mL will be claimed in the labeling.

The high-dose hook effect (HDHE) of the Elecsys AFP assay was assessed on one cobas e 601 analyzer in two-fold determination. No hook effect was seen up to 1,000,000 for both samples.

Seven endogenous substances were evaluated for potential interference with the Elecsys AFP assay on the cobas e 601 analyzer. All predefined acceptance criteria was met, and the proposed labeling claims for each endogenous substance can be found below:

Biotin ≤ 1200 ng/mL Lipemia (Intralipid) ≤ 1500 mg/dL Hemoglobin < 2200 mg/dL Bilirubin ≤ 65 mg/dL Rheumatoid Factor ≤ 1500 IU/mL Serum Albumin ≤ 7 g/dL IgG < 7 g/dL

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An exogenous interference study was conducted to evaluate 17 commonly used and ten specially used pharmaceutical compounds for potential interference with the Elecsys AFP assay on the cobas e 601 analyzer. The predefined acceptance criteria was met for all drugs tested, and no interference was observed.

A method comparison was performed with the current Elecsys AFP assay (material number 04481798190) and the candidate Elecsys AFP assay (material number 09015060160), using a total of 181 serum sample concentrations were between 1.58 and 966 IU/mL. The results can be found below:

Linear regression

- v = -0.148 + 0.969x r = 0.999
Passing/Bablok

y = 0.101 + 0.965x

tau = 0.985

The effect on quantitation of analyte in the presence of anticoagulants with Elecsys AFP was determined by comparing values obtained from native, single-donor samples drawn into serum, Li-Heparin, K2-EDTA, and K3-EDTA plasma primary tubes. All predefined acceptance criteria was met, supporting the labeling claim that serum, Li-Heparin, K2-EDTA and K3-EDTA plasma primary tubes are acceptable sample types.

On-board reagent stability for the Elecsys AFP assay was tested on one cobas e 601 analyzer. Elecsys AFP reagent kits can be stored on-board the analyzers for up to 28 days (4 weeks). A new calibration of the kit kept on-board is recommended every 7 days.

Lot calibration frequency for the Elecsys AFP assay was tested on one cobas e 601 analyzer. Calibrations of an Elecsys AFP reagent lot is recommended every 4 weeks (1 month). During that time period, fresh reagent kits of the same lot can be used without calibration using the calibration curve of the day 0 reagent kit.

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The information provided in this 510(k) Premarket Notification supports the determination that the updated Elecsys AFP is substantially equivalent to the predicate device, Elecsys AFP (K981282).