U.S. Food & Drug Administration 10903 New Hampshire Avenue Doc ID# 04017.04.06 Silver Spring, MD 20993 www.fda.gov Roche Diagnostics August 13, 2019 Jamie Ferguson Regulatory Affairs Principal 9115 Hague Road Indianapolis, Indiana 46250 Re: K190428 Trade/Device Name: Elecsys Anti-HAV II Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A Virus (HAV) Serological Assays Regulatory Class: Class II Product Code: LOL, QCH Dated: February 20, 2019 Received: February 22, 2019 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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U.S. Food & Drug Administration
10903 New Hampshire Avenue D o c I D # 0 4 0 1 7 . 0 4 . 0 6
Silver Spring, MD 20993
www.fda.gov
Roche Diagnostics August 13, 2019
Jamie Ferguson
Regulatory Affairs Principal
9115 Hague Road
Indianapolis, Indiana 46250
Re: K190428
Trade/Device Name: Elecsys Anti-HAV II
Regulation Number: 21 CFR 866.3310
Regulation Name: Hepatitis A Virus (HAV) Serological Assays
Regulatory Class: Class II
Product Code: LOL, QCH
Dated: February 20, 2019
Received: February 22, 2019
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
For the Elecsys Anti-HAV II, the establishment registration number for Roche Diagnostics GmbH in Mannheim, Germany is 9610126, and for Penzberg, Germany, 9610529. The establishment registration number for Roche Diagnostics in the United States is 1823260.
• AHAV 2 Cal2: Positive Calibrator 2 (anti-HAV (human), approximately 60 IU/L in
human serum)
PreciControl Anti-HAV II is a ready-for-use control serum based on human serum both in the
negative and positive concentration range. The controls are used for monitoring the performance
of the Elecsys Anti-HAV II immunoassay. PreciControl Anti-HAV II is sold separately from the
Elecsys Anti-HAV II immunoassay reagent.
2. INTENDED USE
Immunoassay for the in vitro qualitative detection of total antibodies (IgG and IgM) to hepatitis
A virus (HAV) in human pediatric (ages 2 through 21 years) and adult serum and plasma (Li-
Heparin, potassium EDTA, Na-Citrate, Na-Heparin). The assay, in conjunction with other
Roche Diagnostics Elecsys Anti-HAV II Indianapolis, IN 46250 510(k) Summary
Page 4
serological and clinical information, is indicated as an aid in the clinical laboratory diagnosis of
acute or past hepatitis A virus infection in persons with signs or symptoms of hepatitis and in
persons at increased risk for hepatitis A infection, or as an aid to identify HAV susceptible
individuals and to determine the presence of an antibody response to HAV in vaccine recipients.
The electrochemiluminescence immunoassay “ECLIA” is intended for use on the cobas e
immunoassay analyzers.
Assay performance characteristics have not been established for immunocompromised or
immunosuppressed patients. This assay has not been FDA cleared or approved for the screening
of blood or plasma donors.
3. TECHNOLOGICAL CHARACTERISTICS
Elecsys Anti-HAV II utilizes electrochemiluminescence “ECLIA” technology for the qualitative
detection of total antibodies (IgG and IgM) to the hepatitis A virus (HAV) in human pediatric
(ages 2 through 21 years) and adult serum and plasma on the cobas e 601 immunoassay
analyzer.
The following tables compare the Elecsys Anti-HAV II with its predicate device, Elecsys Anti-
HAV (K100903).
Roche Diagnostics Elecsys Anti-HAV II Indianapolis, IN 46250 510(k) Summary
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Table 1: Assay Comparison
Feature Elecsys Anti-HAV (K100903) Elecsys Anti-HAV II
Intended Use/Indications for Use
Immunoassay for the in vitro qualitative detection of total antibodies (IgM and IgG) to hepatitis A virus in human serum and plasma (K2-EDTA). The assay is intended for use as an aid in the laboratory diagnosis of past or acute/recent hepatitis A infection. Assay results, in conjunction with other laboratory results and clinical information, may be used to provide presumptive evidence of infection with hepatitis A virus in persons with signs or symptoms of hepatitis and in persons at risk for hepatitis A infection, or used as an aid to determine the presence of antibody response to HAV in vaccine recipients. The electrochemiluminescence immunoassay “ECLIA” is intended for use on Elecsys and cobas e immunoassay analyzers. This assay is not intended for screening blood or solid or soft tissue donors. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. The users are responsible for establishing their own assay performance characteristics in these populations.
Immunoassay for the in vitro qualitative detection of total antibodies (IgG and IgM) to hepatitis A virus (HAV) in human pediatric (ages 2 through 21 years) and adult serum and plasma (Li-Heparin, potassium EDTA, Na-Citrate, Na-Heparin). The assay, in conjunction with other serological and clinical information, is indicated as an aid in the clinical laboratory diagnosis of acute or past hepatitis A virus infection in persons with signs or symptoms of hepatitis and in persons at increased risk for hepatitis A infection, or as an aid to identify HAV susceptible individuals and to determine the presence of an antibody response to HAV in vaccine recipients. The electrochemiluminescence immunoassay “ECLIA” is intended for use on cobas e immunoassay analyzers. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients. This assay has not been FDA cleared or approved for the screening of blood or plasma donors.
Assay Method Competition principle binding protein Same
Detection Method Electrochemiluminescence Same
Applications/Test Time 18 minutes Same
Instrument Platform Elecsys 2010, cobas e 411, cobas e 601, cobas e 602, and MODULAR ANALYTICS E170
Calibrator Anti-HAV Cal1 and Cal2 (packed in kit) Anti-HAV II Cal1 and Cal2 (packed in kit)
Calibration Method 2-point calibration Same
Roche Diagnostics Elecsys Anti-HAV II Indianapolis, IN 46250 510(k) Summary
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Feature Elecsys Anti-HAV (K100903) Elecsys Anti-HAV II
Calibration Interval
Calibration must be performed once per reagent lot using fresh reagent (i.e. not more than 24 hours since the reagent kit was registered on the analyzer). Renewed calibration is recommended as follows:
• after 1 month (28 days) when using the same reagent lot
• after 7 days (when using the same reagent kit on the analyzer)
• as required: e.g. quality control findings outside the defined limits
Same
Controls PreciControl Anti-HAV PreciControl Anti-HAV II
Traceability/Standardization Second International Standard for Anti Hepatitis A, Immunoglobulin, Human, NIBSC code: 97/646
Same
Reagent Stability
Store at 2-8°C. Do not freeze. Store the Elecsys reagent kit upright in order to ensure complete availability of the microparticles during automatic mixing prior to use. Unopened at 2-8°C, up to stated expiration date. After opening at 2-8°C, 8 weeks. On the analyzers at 20-25°C, 7 days or 4 weeks when stored alternative in the refrigerator and on the analyzer, with the total time onboard on the analyzer not exceeding 40 hours.
Store at 2-8°C. Do not freeze. Store the Elecsys reagent kit upright in order to ensure complete availability of the microparticles during automatic mixing prior to use. Unopened at 2-8°C, up to stated expiration date. After opening at 2-8°C, 8 weeks. On the analyzers at 20-25°C, 8 weeks.
Roche Diagnostics Elecsys Anti-HAV II Indianapolis, IN 46250 510(k) Summary
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Feature Elecsys Anti-HAV (K100903) Elecsys Anti-HAV II
Limitations
Bilirubin < 855 µmol/L or < 50 mg/dL Hemolysis < 0.623 mmol/L or < 1.0 g/dL Lipemia < 1500 mg/dL Biotin < 205 nmol/L or < 50 ng/mL Criterion: Recovery within +/- 20% of initial value Samples should not be taken from patients receiving therapy with high biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin administration. In vitro tests were performed on 18 commonly used pharmaceuticals (Acetylcystein, Ampicillin, Ascorbic acid, Ca Dobesilate, Cyclosporine, Cefoxitin, Heparin, Intralipid, Levodopa, Methyldopa, Metronidazole, Phenylbutazone, Tetracycline, Acetylsalicylic Acid, Rifampicin, Acetaminophen, Ibuprofen and Theophylline). No interference with the assay was found. In rare cases, interference due to extremely high titers of antibodies to analyte specific antibodies, streptavidin or ruthenium can occur. These effects are minimized by suitable test design.
Bilirubin < 1129 µmol/L or ≤ 66 mg/dL Hemoglobin ≤ 0.621 mmol/L or ≤ 1000 mg/dL Intralipid ≤ 2000 mg/dL Rheumatoid Factors ≤ 1400 IU/mL IgG ≤ 7.0 g/dL IgA ≤ 1.6 g/dL IgM ≤ 1.0 g/dL Serum Albumin ≤ 7 g/dL Criterion: > 1.0 COI +/- 20% recovery, ≤ 1.0 COI +/- 0.20 recovery Negative specimens with biotin concentrations up to 100 ng/mL demonstrated ≤ 11 % negative bias in COI values. Biotin concentrations greater than 100 ng/mL lead to higher negative bias and in consequence can lead to false positive Elecsys Anti-HAV II results. Some studies have shown that serum concentrations of biotin can reach up to 355 ng/mL within the first hour after ingestion for subjects consuming supplements of 20 mg biotin per day and up to 1160 ng/mL in plasma for subjects consuming a single dose of 300 mg biotin. In vitro tests were performed on 18 commonly used pharmaceuticals (Acetylcystein, Ampicillin-Na, Ascorbic acid, Ca Dobesilate, Cyclosporine, Cefoxitin, Doxycycline, Heparin, Levodopa, Methyldopa +1.5, Metronidazole, Phenylbutazone, Tetracycline, Acetylsalicylic Acid, Rifampicin, Acetaminophen, Ibuprofen and Theophylline). No interference with the assay was found. In rare cases, interference due to extremely high titers of antibodies to analyte specific antibodies, streptavidin or ruthenium can occur. These effects are minimized by suitable test design.
Roche Diagnostics Elecsys Anti-HAV II Indianapolis, IN 46250 510(k) Summary
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4. NON-CLINICAL PERFORMANCE EVALUATION
Non-clinical performance evaluation for Elecsys Anti-HAV II is briefly summarized below.
4.1. Precision
4.1.1. Repeatability and Within-Laboratory Precision
Precision measurements were conducted to evaluate repeatability (within-run precision) and
within-laboratory precision (intermediate precision) in a study based on the protocol of CLSI
EP05-A3. Precision was evaluated on a single cobas e 601 immunoassay analyzer. One Elecsys
Anti-HAV II reagent lot was evaluated. The protocol consisted of testing 2 aliquots each of two
levels of control and 5 human sera per run, 2 runs per day for 21 days. Calibration was
performed on day 1 and on day 17. Serum samples were human serum sample pools.
Table 2: Repeatability and Within-Laboratory Precision Results
e) Cutoff of 1.0 COI used for Elecsys Anti-HAV II assay f) Specimens with results in the borderline range of (18.0 ≤ IU/L < 22.0) for Elecsys Anti-HAV assay were counted as discordant with the Elecsys Anti-HAV II assay
5.3. Pre- and Post-HAV Vaccination
Specimens from 49 subjects that were collected both pre- and post-HAV vaccination were
evaluated by the Elecsys Anti-HAV II assay and the predicate assay (Elecsys Anti-HAV). The
post-vaccination specimens were obtained at least 4 weeks, but not more than 10 weeks, after the
completion of the vaccine regimen. Three HAV vaccines, which are currently licensed in the
U.S., were used. No discrepant results were observed.
5.4. Prevalence Study
The Elecsys Anti-HAV II assay was used to evaluate the prevalence of HAV antibodies in an
apparently healthy population (presumed normal, healthy individuals without symptoms derived
by a self-reporting health questionnaire). A statistically significant number of subjects were
collected in a presumed “high prevalence” region, the Western United States, and a presumed
Roche Diagnostics Elecsys Anti-HAV II Indianapolis, IN 46250 510(k) Summary
Page 21
“low prevalence” region, the Eastern United States. Testing based on the predicate assay was
not required.
The collection site representing the Eastern US recruited 431 subjects. Of the 431 subject, 31
were classified as screen failures and therefore did not complete the informed consent process.
A total of 400 subjects satisfied the inclusion/exclusion criteria and proved acceptable specimens
for analysis. The collection site representing the Western US recruited 427 subjects. Of the 427
subjects, 24 were classified as screen failures and therefore did not complete the informed
consent process. An additional three subjects were dropped from enrollment. A subject was
allowed to be dropped from enrollment if defined conditions were met after the screening
process was completed and the informed consent process was successfully completed. Both
collection sites were open to the recruitment/enrollment of subjects for Prevalence cohort only.
Each site was instructed to collect 400 evaluable specimens, which was accomplished.
The results were consistent with a higher prevalence of reactive HAV results reported in the
Western US, 53.75%, versus the Eastern US 29.50%.
6. ADDITIONAL INFORMATION
The Elecsys Anti-HAV II is intended to be used with the following calibrators and controls:
• PreciControl Anti-HAV II
• Anti-HAV II Cal1 and Anti-HAV II Cal2, which is included in the kit
7. CONCLUSIONS
The information provided in this 510(k) Premarket Notification supports a determination of
substantial equivalence for the Elecsys Anti-HAV II. The data from the non-clinical and clinical
tests demonstrate that the device is as safe, as effective, and performs as well as the predicate