ADVIA Centaur HAV IgM Assay

K161964 · Siemens Healthcare Diagnostics, Inc. · LOL · Oct 13, 2016 · Microbiology

Device Facts

• Record ID: K161964
• Device Name: ADVIA Centaur HAV IgM Assay
• Applicant: Siemens Healthcare Diagnostics, Inc.
• Product Code: LOL · Microbiology
• Decision Date: Oct 13, 2016
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3310
• Device Class: Class 2
• Attributes: Pediatric

Indications for Use

The ADVIA Centaur® HAV IgM (aHAVM) assay is an in vitro diagnostic immunoassay for the qualitative determination of IgM response to the hepatitis A virus (HAV) in human pediatric (2 through 21 years) and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur XP, and ADVIA Centaur XPT systems. This assay is intended for use as an aid in the diagnosis of acute or recent infection (usually 6 months or less) with hepatitis A virus. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, or patients less than 2 years of age. The ADVIA Centaur® HAV IgM (aHAVM) assay is an in vitro diagnostic immunoassay for the qualitative determination of IgM response to the hepatitis A virus (HAV) in human pediatric (2 through 21 years) and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur CP system. This assay is intended for use as an aid in the diagnosis of acute or recent infection (usually 6 months or less) with hepatitis A virus. Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, or patients less than 2 years of age.

Device Story

ADVIA Centaur HAV IgM assay is an automated in vitro diagnostic immunoassay for detecting IgM antibodies to hepatitis A virus. It utilizes a 2-pass IgM capture principle on ADVIA Centaur instrument family systems (XP, XPT, CP). Input: human serum or plasma. Process: sample diluted; biotinylated anti-human IgM monoclonal antibody binds patient IgM; complex captured by streptavidin-coated paramagnetic microparticles; washed; detected via sequential addition of HAV antigen and acridinium ester-labeled mouse anti-HAV antibody. Output: qualitative result indicating presence/absence of HAV IgM. Used in clinical laboratories by trained technicians. Results assist physicians in diagnosing acute or recent HAV infection. Benefits include automated, standardized testing for pediatric and adult populations.

Clinical Evidence

Clinical study evaluated 132 pediatric serum samples (ages 2-21) from suspected positive or high-risk populations. Compared ADVIA Centaur HAV IgM assay against a commercially available assay. Results: 90.9% positive agreement (95% CI: 75.67%–98.08%) and 98.98% negative agreement (95% CI: 94.45%–99.97%).

Technological Characteristics

IgM capture immunoassay using chemiluminescence. Reagents: biotinylated anti-human IgM monoclonal antibody, streptavidin-coated paramagnetic microparticles, HAV antigen, and acridinium ester-labeled mouse anti-HAV monoclonal antibody (Fab fragments). Automated system (ADVIA Centaur family).

Indications for Use

Indicated for qualitative determination of IgM response to hepatitis A virus (HAV) in human pediatric (2-21 years) and adult serum or plasma. Used as an aid in diagnosis of acute or recent (≤6 months) HAV infection. Not established for immunocompromised/immunosuppressed patients, cord blood, or children <2 years.

Regulatory Classification

Identification

HAV serological assays are devices that consist of antigens and antisera for the detection of hepatitis A virus-specific IgM, IgG, or total antibodies (IgM and IgG), in human serum or plasma. These devices are used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis to determine if an individual has been previously infected with HAV, or as an aid to identify HAV-susceptible individuals. The detection of these antibodies aids in the clinical laboratory diagnosis of an acute or past infection by HAV in conjunction with other clinical laboratory findings. These devices are not intended for screening blood or solid or soft tissue donors.

Special Controls

*Classification.* Class II (special controls). The special control is “Guidance for Industry and FDA Staff: Class II Special Controls Guidance Document: Hepatitis A Virus Serological Assays.” See § 866.1(e) for the availability of this guidance document.

Predicate Devices

• VITROS® Anti-HAV Immunodiagnostic Products IgM Reagent Pack (K060770)

Submission Summary (Full Text)

{0}

1

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number: K161964
B. Purpose for Submission: To support the addition of the pediatric population testing to the Intended Use/Indications for Use for the ADVIA Centaur® HAV IgM assay cleared under K081716 (originally approved under PMA P040018).
C. Measurand: Hepatitis A virus (HAV) IgM antibodies
D. Type of Test: Enzyme immunoassay
E. Applicant: Siemens Healthcare Diagnostics
F. Proprietary and Established Names: ADVIA® Centaur HAV IgM Assay

## G. Regulatory Information:

1. Regulation section: 21 CFR §866.3310; Hepatitis A virus (HAV) serological assays
2. Classification: Class II
3. Product code: LOL; Hepatitis A test (antibody and IgM antibody)
4. Panel: Microbiology

## H. Intended Use:

1. Intended use(s):

**ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT systems:**

The ADVIA Centaur® HAV IgM (aHAVM) assay is an in vitro diagnostic immunoassay for the qualitative determination of IgM response to the hepatitis A virus (HAV) in human pediatric (2 through 21 years) and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT systems. This assay is intended for use as an aid in the diagnosis of acute or recent infection (usually 6 months or less) with hepatitis A virus.

Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, or patients less than 2 years of age.

**ADVIA Centaur CP system:**

The ADVIA Centaur® HAV IgM (aHAVM) assay is an in vitro diagnostic immunoassay for the qualitative determination of IgM response to the hepatitis A virus (HAV) in human pediatric (2 through 21 years) and adult serum or plasma (potassium EDTA,

{1}

lithium or sodium heparinized) using the ADVIA Centaur CP system. This assay is intended for use as an aid in the diagnosis of acute or recent infection (usually 6 months or less) with hepatitis A virus.

Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, cord blood, or patients less than 2 years of age.

2. Indication(s) for use:

Same as Intended Use

3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

ADVIA Centaur, ADVIA Centaur XP, ADVIA Centaur XPT, or ADVIA Centaur CP system.

I. Device Description:

The ADVIA Centaur HAV IgM assay is an IgM capture immunoassay. In the first step, the sample is diluted using Multi-Diluent 2. After sample dilution, biotinylated anti-human IgM monoclonal antibody is added to the cuvette binding IgM from the diluted patient sample. The IgM complex is then captured by the addition of streptavidin coated magnetic latex particles (MLP). The IgM-MLP is washed and resuspended. The anti-HAV IgM captured on the Solid Phase is then detected by the sequential addition of HAV antigen and acridinium ester-labeled mouse anti-HAV antibody.

J. Substantial Equivalence Information:

1. Predicate device name(s):

VITROS® Anti-HAV Immunodiagnostic Products IgM Reagent Pack

2. Predicate 510(k) number(s):

K060770

{2}

3

3. Comparison with predicate:

Similarities:

| Item | Modified Device: ADVIA Centaur HAV IgM Assay | Predicate Device: VITROS Immunodiagnostic Products Anti-HAV IgM Reagent |
| --- | --- | --- |
| Intended Use | For the qualitative determination of IgM response to hepatitis A virus (anti-HAV IgM) in human, pediatric (2 through 21 years) and adult samples | For the qualitative determination of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human adult and pediatric samples |
| Indications for Use | This assay is intended for use as an aid in the diagnosis of acute or recent infection (usually 6 months or less) with hepatitis A virus. | The assay is indicated for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis. Assay results, in conjunction with other clinical information, may be used for the laboratory diagnosis of individuals with acute or recent hepatitis A. |
| Sample type | Serum and Plasma | Same |
| Measurement | Qualitative | Same |
| Assay Principle | IgM capture immunoassay | Same |
| Technology | Chemiluminescence | Same |

Differences:

| Item | Modified Device: ADVIA Centaur HAVT Assay | Predicate Device: VITROS Immunodiagnostic Products Anti-HAV IgM Reagent |
| --- | --- | --- |
| Standardization / Traceability | The cutoff for the ADVIA Centaur HAV IgM assay was verified based on results of Receiver-Operator characteristics (ROC) Curve and clinical agreement generated from the clinical studies. | Traceable to an in-house reference calibrator which has been value assigned to optimize the clinical sensitivity and specificity performance. |
| Detection Antibody | Mouse monoclonal anti-HAV antibody Fab fragments labeled with acridinium ester | Mouse monoclonal anti-HAV antibody labeled with horseradish peroxidase (HRP) |
| Capture Antibody | Mouse monoclonal to anti-human IgM antibody labeled with biotin | Mouse monoclonal to anti-human IgM antibody labeled with biotin |

K. Standard/Guidance Document Referenced (if applicable): N/A

L. Test Principle: Enzyme Immunoassay

{3}

M. Performance Characteristics (if/when applicable):

NOTE: Performance Characteristics of the ADVIA Centaur HAV IgM assay other than the pediatric population studies have been established under parent documents, P040018 and K081716.

1. Analytical performance:

a. Precision/Reproducibility:
See the Summary of Safety and Effectiveness Data for P040018.

b. Linearity/assay reportable range: N/A
c. Traceability, Stability, Expected values (controls, calibrators, or methods): N/A
d. Detection limit: N/A
e. Analytical specificity:
Cross Reactivity: See the Summary of Safety and Effectiveness Data for P040018.
Interferences: See the Summary of Safety and Effectiveness Data for P040018.
f. Assay cut-off:
See the Summary of Safety and Effectiveness Data for P040018.

2. Comparison studies:

a. Method comparison with predicate device:
Pediatric Patient Testing: The following comparison study was performed to demonstrate that the pediatric population can be used in the ADVIA Centaur HAV IgM assay. One hundred and thirty-two (132) pediatric serum samples (male and female, age range from 2 to 21 years), from suspected positive or high risk population were evaluated with the ADVIA Centaur HAV IgM assay and another commercially available assay. The percent agreement results are shown in the following table:

4

{4}

5

Comparative anti-HAV IgM Assay

| ADVIA Centaur
Anti-HAV IGM Assay | Reactive | Borderline
Reactive | Non- reactive | Total |
| --- | --- | --- | --- | --- |
| Reactive | 30 | 0 | 0 | 30 |
| Equivocal | 0 | 1 | 1 | 2 |
| Non- reactive | 1 | 2* | 97 | 100 |
| Total | 31 | 3 | 98 | 132 |

* Included in the total number of samples (n=33) in the calculation of % Positive Agreement

% Positive Agreement = 90.9% (30/33)

95% Confidence Interval = 75.67% to 98.08%

% Negative Agreement = 98.98% (97/98)

95% Confidence Interval = 94.45% to 99.97%

Prospective Study: See the Summary of Safety and Effectiveness Data for P040018.

b. Matrix comparison: N/A

3. Clinical studies:

a. Clinical Sensitivity: N/A
b. Clinical specificity: N/A
c. Other clinical supportive data (when a. and b. are not applicable): N/A

4. Clinical cut-off: N/A

5. Expected values/Reference range:

See the Summary of Safety and Effectiveness Data for P040018.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.