Elecsys Anti-HCV II (08837031190)

K221693 · Roche Diagnostics · MZO · Jan 4, 2023 · Microbiology

Device Facts

• Record ID: K221693
• Device Name: Elecsys Anti-HCV II (08837031190)
• Applicant: Roche Diagnostics
• Product Code: MZO · Microbiology
• Decision Date: Jan 4, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3169
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

lmmunoassay for the in vitro qualitative detection of antibodies to hepatitis C virus (HCV) in human adult and pediatric (ages 18 months through 21 years) serum and plasma (potassium EDTA, lithium heparin, sodium heparin, and sodium citrate). Assay results, in conjunction with other laboratory results and clinical information, may be used to aid in the presumptive diagnosis of HCV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis C infection. The test does not determine the state of infection or associated disease. The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.

Device Story

In vitro diagnostic immunoassay; detects total antibodies to HCV in human serum/plasma. Uses two-step sandwich ECLIA technology; 18-minute duration. Input: 50 µL sample + biotinylated HCV antigens + ruthenium-labeled HCV antigens. Process: formation of sandwich complex; binding to streptavidin-coated microparticles; magnetic capture on electrode; chemiluminescent emission induced by voltage; measured by photomultiplier. Used in clinical laboratories on cobas e immunoassay analyzers. Software automatically compares signal to calibration cut-off to determine qualitative result. Updated version includes streptavidin interference reducing agent to improve biotin tolerance (up to 1200 ng/mL). Results aid clinicians in presumptive diagnosis of HCV infection; supports clinical decision-making when combined with other laboratory/clinical data.

Clinical Evidence

Bench testing only. Precision studies (single and multi-analyzer) confirmed reproducibility with CV < 4.5%. Interference testing validated biotin tolerance up to 1200 ng/mL. Method comparison study (n=219) between current and updated assay showed overall PPA of 96.33% (95% CI: 90.94-98.56%) and NPA of 99.63% (95% CI: 95.27-100.00%). Regression analysis and bias estimation confirmed comparability.

Technological Characteristics

Two-step sandwich electrochemiluminescence immunoassay (ECLIA). Reagents: biotinylated HCV antigens, ruthenium-labeled HCV antigens, streptavidin-coated microparticles. Includes streptavidin interference reducing agent. Analyzers: cobas e series. Detection: photomultiplier-based chemiluminescence. Biotin tolerance: ≤ 1200 ng/mL. Software: automated signal processing and cut-off comparison.

Indications for Use

Indicated for in vitro qualitative detection of anti-HCV antibodies in human serum and plasma (potassium EDTA, lithium heparin, sodium heparin, sodium citrate) for adults and pediatric patients (18 months to 21 years). Used to aid presumptive diagnosis of HCV infection in symptomatic individuals or those at risk. Does not determine infection state or disease status.

Regulatory Classification

Identification

A hepatitis C virus (HCV) antibody test is identified as an in vitro diagnostic device intended for use with human serum, plasma, or other matrices as a prescription device that aids in the diagnosis of HCV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis C infection. The test is not intended for screening blood, plasma, cell, or tissue donors.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the test is not intended for the screening of blood, plasma, and cell or tissue donors. (ii) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: (A) When appropriate, the performance characteristics of the test have not been established in populations of immunocompromised or immunosuppressed patients or, other special populations where test performance may be affected. (B) The detection of HCV antibodies indicates a present or past infection with hepatitis C virus, but does not differentiate between acute, chronic, or resolved infection. (C) The specimen types for which the device has been cleared, and that use of the test with specimen types other than those specifically cleared for this device may result in inaccurate test results. (D) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results. (E) A non-reactive test result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the test. (iii) A detailed explanation of the principles of operation and procedures for performing the test. (2) Design verification and validation must include the following: (i) A detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, and design of the antigen(s) and capture antibody(ies) sequences, rationale for the selected epitope(s), degree of amino acid sequence conservation of the target, and the design and nature of all primary, secondary, and subsequent standards used for calibration. (ii) Documentation and characterization ( *e.g.,* supplier, determination of identity, and stability) of all critical reagents (including description of the antigen(s) and capture antibody(ies)), and protocols for maintaining product integrity throughout its labeled shelf life.(iii) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (iv) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (v) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vi) All stability protocols, including acceptance criteria. (vii) Final release test results for each lot used in clinical studies. (viii) Multisite reproducibility study that includes the testing of three independent production lots. (ix) Analytical performance studies and results for determining the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility) including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, specimen stability, reagent stability, and cross-genotype antibody detection sensitivity, when appropriate. (x) Analytical sensitivity of the test is the same or better than that of other cleared or approved tests. (xi) Detailed documentation of clinical performance testing from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved HCV antibody test, or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with an acceptable number of HCV positive and negative samples in applicable risk categories. Additional relevant patient groups must be validated as appropriate. The samples may be a combination of fresh and repository samples, sourced from geographically diverse areas. The study designs, including number of samples tested, must be sufficient to meet the following criteria: (A) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 95 percent. (B) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 96 percent. (3) For any HCV antibody test intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Clinical studies must be conducted at PoC sites. (ii) Additional labeling must include a brief summary of the instructions for use that are appropriate for use in a PoC environment.

Predicate Devices

• Elecsys Anti-HCV II Immunoassay (P140021)

Submission Summary (Full Text)

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January 4, 2023

Image /page/0/Picture/1 description: The image shows 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: K221693

Trade/Device Name: Elecsys Anti-HCV II (08837031190) Regulation Number: 21 CFR 866.3169 Regulation Name: Hepatitis C Virus Antibody Tests Regulatory Class: Class II Product Code: MZO Dated: June 9, 2022 Received: June 10, 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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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 (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 ([e-mail]) or phone [phone] 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 Anti-HCV II (08837031190)

#### Indications for Use (Describe)

lmmunoassay for the in vitro qualitative detection of antibodies to hepatitis C virus (HCV) in human adult and pediatric (ages 18 months through 21 years) serum and plasma (potassium EDTA, lithium heparin, sodium heparin, and sodium citrate). Assay results, in conjunction with other laboratory results and clinical information, may be used to aid in the presumptive diagnosis of HCV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis C infection. The test does not determine the state of infection or associated disease.

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: 2022-06-09

### 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 | [e-mail] |

Device Name
21 CFR 807.92(a)(2)

| Device Trade Name | Elecsys Anti-HCV II (08837031190) |
|---------------------|-------------------------------------------------------|
| Common Name | Hepatitis C virus antibody tests |
| Classification Name | Assay, Enzyme Linked Immunosorbent, Hepatitis C Virus |
| Regulation Number | 866.3169 |
| Product Code | MZO |

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

| Predicate # | Predicate Trade Name (Primary Predicate is listed first) | Product Code |
|-------------|----------------------------------------------------------|--------------|
| P140021 | Elecsys Anti-HCV II Immunoassay | MZO |

Device Description Summary 21 CFR 807.92(a)(4)
Immunoassay for the in vitro qualitative detection of antibodies to hepatitis C virus (HCV) in human adult and pediatric (ages 18 months through 21 years) serum and plasma (potassium EDTA, lithium heparin, sodium heparin, and sodium citrate). Assay results, in conjunction with other laboratory results and clinical information, may be used to aid in the presumptive diagnosis of HCV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis C infection. The test does not determine the state of infection or associated disease.
The electrochemiluminescence immunoassay "ECLIA" is intended for use on cobas e immunoassay analyzers.
The Elecsys Anti-HCV II Immunoassay employs "ECLIA" technology and is a qualitative serologic, two step sandwich assay. The assay detects total antibodies to HCV in serum and plasma samples. The total duration of the assay is 18 minutes. The basic device methodology is as follows:
1. 1st incubation: 50 µL of sample, 55 µL of a reagent containing biotinylated HCV antigens, and 55 µL of a reagent containing HCV antigens labeled with a ruthenium complex react to form a sandwich complex.
2. 2nd incubation: After addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.
3. 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. Application of a voltage to the electrode then induces chemiluminescent emission, which is measured by a photomultiplier.
4. Results are determined automatically by the Elecsys software by comparing the electrochemiluminescence signal obtained from the sample with the cut-off value obtained by the anti-HCV calibration.
Intended Use/Indications for Use 21 CFR 807.92(a)(5)lmmunoassay for the in vitro qualitative detection of antibodies to hepatitis C virus (HCV) in human adult and pediatric (ages 18 months

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through 21 years) serum and plasma (potassium EDTA, lithium heparin,

sodium heparin, and sodium citrate). Assay results, in conjunction with other laboratory results and clinical information, may be used to aid in the presumptive diagnosis of HCV infection in persons with signs and

symptoms of hepatitis and in persons at risk for hepatitis C infection. The test does not determine the state of infection or associated disease.

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

### Indications for Use Comparison

Elecsys Anti-HCV II (updated assay, Mat. No. 08837031190) is substantially equivalent to Elecsys Anti-HCV II, approved under P14021.

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

### Technological Comparison

Roche Diagnostics has updated the current Elecsys Anti-HCV II assay in order to improve the biotin tolerance from ≤ 44 ng/mL to ≤ 1200 ng/mL and to reduce streptavidin interference. A technical solution was implemented by adding an the reagents, which allows depletion of biotin in patient samples by binding 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

### 1. Precision

The precision of the Elecsys Anti-HCV II assay was evaluated on one cobas e 601 immunoassay analyzer with one reagent lot. The protocol consisted of testing 2 aliquots of each of controls and 5 human serum samples per run, 2 runs per day for 12 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. All predefined acceptance criteria was met for the precision experiments.

### 2. Biotin Interference

The effect on measuring of analyte in the presence of biotin using the Elecsys Anti-HCV I assay was determined using three serum samples (negative, low positive and moderate positive) with three lots according to CLSI EP07-A3 Appendix A.

Unique negative serum was used for negative and moderate positive samples were each prepared from unique negative serum spiked with unique anti-HCV positive serum. 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 17 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. No biotin interference was observed up to 2520 ng/mL. The biotin claim in 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 performance of the current Elecsys Anti-HCV II assay and the biotin-updated Elecsys Anti-HCV II assay on one cobas e 601 analyzer.

A total of 219 samples were measured with one reagent lot of the current Elecsys Anti-HCV II assay and three different reagent lots of the biotin-updated Elecsys Anti-HCV II assay in single determination on the cobas e 601 analyzer. Results are presented in a 3x3 table. Positive Agreement and Negative Agreen 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.

On-board reagent stability for the Elecsys Anti-HCV II assay was tested on one cobas e 601 analyzer. Elecsys Anti-HCV II reagent kits can be stored on-board the analyzers for up to 31 days.

Lot calibration frequency for the Elecsys Anti-HCV II was tested on one cobas e 601 analyzer. The study confirm calibration stability of one month (28 days) with multiple kits from the same reagent lot. Calibrations of an Elecsys Anti-HCV I reagent lot is recommended every 4 weeks when using the same reagent lot.

Real-time stability was tested on one cobas e 601 analyzer. Data supporting a shelf-life of 12 months.

#### Not Applicable

## 21 CFR 807.92(a)(5)

21 CFR 807.92(a)(6)

21 CFR 807.92(b)