The ADVIA Centaur HAV Total (HAVT) assay is an in vitro diagnostic immunoassay for the qualitative deternination of total antibodies to hepatitis A virus (anti-HAV) in human neonatal, pediatric, and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur XP systems. This anti-HAV assay is indicated as an aid in the diagnosis of previous or ongoing hepatitis A viral infection or HAVsusceptible individuals for vaccination.

Assay performance characteristics have not been established for immunosompromised or immunosuppressed patients.

WARNING: This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

United States federal law restricts this device to sale by or on the order of a physician.

ADVIA Centaur CP system:

The ADVIA Centaur HAV Total (HAVT) assay is an in vitro diagnostic immunoassay for the qualitative deternination of total antibodies to hepatitis A virus (anti-HAV) in human neonatal, pediatric, and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur CP system. This anti-HAV assay is indicated as an aid in the diagnosis of previous or ongoing hepatitis A viral infection of HAV-susceptible individuals for vaccination.

Assay performance characteristics have not been established for immunosuppressed patients.

WARNING: This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

United States federal law restricts this device to sale by or on the order of a physician.

Device Description

The ADVIA Centaur HAVT reagent kit contains the following:

ReadyPack primary reagent pack containing ADVIA Centaur HAVT Lite Reagent, Solid Phase Reagent, and Antigen Reagent
ReadyPack ancillary pack containing ADVIA Centaur HAVT Ancillary Reagent
ADVIA Centaur HAVT Low Calibrator
ADVIA Centaur HAVT High Calibrator
ADVIA Centaur systems HAVT Master Curve card
ADVIA Centaur systems HAVT Calibrator Assigned Value Card

The HAVT ReadyPack consists of the following:

Primary reagent pack

The Lite Reagent is an anti-human HAV monoclonal antibody (~1.0 ug/mL) labeled with acridinium ester and biotinylated monoclonal mouse anti-HAV Fab fragment (~0.08 µg/mL) in phosphate buffer with bovine serum albumin, sodium azide (< 0.1%) and preservatives
The Solid Phase is a streptavidin coated paramagnetic microparticles in phosphate buffer with bovine serum albumin, sodium azide (< 0.1%) and preservatives
The Antigen Reagent is HAV antigen (~0.06 µg/mL) in tricine buffer with bovine serum albumin, stabilizers, sodium azide (< 0.1%) and preservatives

Ancillary pack

The Ancillary Reagent is cysteine in citrate buffer with EDTA and preservatives

HAVT Calibrators

Processed human plasma positive for anti-HAV antibodies with sodium azide (< 0.1%)

AI/ML Overview

This document describes the request to add neonate and pediatric populations to the intended use statement of the ADVIA® Centaur HAV Total Assay. The submission focuses on demonstrating that the assay's performance remains acceptable for these new populations without requiring a full re-evaluation of all analytical performance characteristics.

Here's the breakdown of the acceptance criteria and study information provided:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state formal acceptance criteria with numerical targets. Instead, it presents study results and implies that "substantially equivalent in principle and performance" to the predicate device (VITROS Immunodiagnostic Products Anti-HAV Total Reagent Pack) for these new populations is the underlying acceptance criterion. The performance data focuses on demonstrating comparable results between adult, neonate, and pediatric samples, and concordance with an existing cleared assay.

Here's a table summarizing the reported device performance for the introduced data:

Study/Metric	Acceptance Criteria (Implied)	Reported Device Performance
Spike/Recovery - Neonatal Cord Blood vs. Adult Serum	Bias distribution demonstrating acceptable similarity.	Negative (0.6 Index): 0.0% ≤ 10% bias, 33.3% > 10% to ≤ 20%, 33.3% > 20% to ≤ 30%, 33.3% > 30%Cut-off (1.0 Index): 16.7% ≤ 10% bias, 33.3% > 10% to ≤ 20%, 50.0% > 20% to ≤ 30%, 0.0% > 30%Low Pos. (1.7 Index): 83.3% ≤ 10% bias, 16.7% > 10% to ≤ 20%, 0.0% > 20% to ≤ 30%, 0.0% > 30%High Pos. (5.8 Index): 83.3% ≤ 10% bias, 16.7% > 10% to ≤ 20%, 0.0% > 20% to ≤ 30%, 0.0% > 30%Total: 53.33% ≤ 10% bias, 23.33% > 10% to ≤ 20%, 16.67% > 20% to ≤ 30%, 6.67% > 30%
Spike/Recovery - Pediatric vs. Adult Serum	Bias distribution demonstrating acceptable similarity.	Negative (0.6 Index): 0.0% ≤ 10% bias, 0.0% > 10% to ≤ 20%, 0.0% > 20% to ≤ 30%, 100.0% > 30%Cut-off (1.0 Index): 66.7% ≤ 10% bias, 16.7% > 10% to ≤ 20%, 16.7% > 20% to ≤ 30%, 0.0% > 30%Low Pos. (1.7 Index): 50.0% ≤ 10% bias, 41.7% > 10% to ≤ 20%, 0.0% > 20% to ≤ 30%, 8.3% > 30%High Pos. (5.8 Index): 83.3% ≤ 10% bias, 16.7% > 10% to ≤ 20%, 0.0% > 20% to ≤ 30%, 0.0% > 30%Total: 50% ≤ 10% bias, 23.33% > 10% to ≤ 20%, 3.33% > 20% to ≤ 30%, 23.33% > 30%
Concordance Study - Pediatric Samples	High positive and negative agreement with comparative assay.	% Positive Agreement: 84.62% (11/13)95% Confidence Interval:* 54.55 to 98.08%% Negative Agreement: 97.62% (41/42)95% Confidence Interval: 87.43 to 99.94%*Note: The 2 borderline results from the comparative assay are scored as discordant results in the %Positive Agreement calculation.

2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

Spike/Recovery studies (Neonatal and Pediatric):
- Test Set Sample Size: 30 neonatal cord blood samples and 30 pediatric serum samples. In both studies, these were compared against 30 adult serum samples.
- Data Provenance: Not specified (e.g., country of origin). The data appears to be prospective in nature, as samples were "spiked with anti-HAV positive stock to yield samples at different analyte levels."
Concordance Study (Pediatric):
- Test Set Sample Size: 55 pediatric serum samples (male and female, age range from 2 to 21 years), including samples from a high-risk population.
- Data Provenance: Not specified (e.g., country of origin). The study "evaluated...samples with the ADVIA Centaur HAVT assay and another commercially available assay," suggesting a retrospective evaluation of collected samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

The studies described in the document do not rely on expert-established ground truth in the traditional sense.

For the spike/recovery studies, the "ground truth" is based on the known spiking concentrations of anti-HAV antibodies and comparison to adult serum samples.
For the concordance study, the "ground truth" is established by a "commercially available assay" which serves as the comparator. No information is provided about experts involved in establishing the results of this comparative assay.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not applicable. The studies are based on quantitative (spike/recovery) or comparative (concordance with another assay) measurements, rather than subjective expert interpretations requiring adjudication.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

Not applicable. This is an in-vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic device that involves human readers interpreting cases.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies presented represent the standalone performance of the ADVIA Centaur HAV Total Assay. It's an automated immunoassay, and its output is a direct measurement (index value) or a qualitative result (Reactive/Nonreactive). There is no human interpretation integrated into the assay's performance evaluation as described.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

Spike/Recovery studies: The ground truth is effectively the known concentration of spiked analyte and the comparison against a referencable population (adult serum).
Concordance study: The ground truth is established by a comparative commercially available assay.

8. The sample size for the training set

The document does not detail specific "training set" information for the submitted studies. The original ADVIA Centaur HAVT assay was approved under PMA P040017, and the current submission is an amendment. The original PMA would have involved extensive studies using a large number of samples for assay development, optimization, and establishment of performance characteristics (which could be considered analogous to a training phase in machine learning, though it's not explicitly called that here). The current submission leverages that prior approval and focuses on bridging data for new populations.

9. How the ground truth for the training set was established

As above, explicit "training set" and its ground truth establishment are not detailed in this specific document. For an IVD assay like this, the "ground truth" for the original PMA approval would typically involve:

Reference materials: Use of well-characterized positive and negative samples, often with known HAV infection status confirmed by other methods (e.g., PCR for viral load, clinical diagnosis, seroconversion panels).
Clinical correlation: Samples from patients with confirmed HAV infections (acute, past) and uninfected individuals.
Comparison to established gold standards: Benchmarking against widely recognized and validated assays.

The goal is to ensure the assay accurately detects the presence or absence of anti-HAV antibodies.

Summary

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December 5, 2014

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

SIEMENS HEALTHCARE DIAGNOSTICS, INC. PHILIP LIU SENIOR MANAGER, REGULATORY AFFAIRS AND COMPLIANCE 511 BENEDICT AVENUE TARRYTOWN NY 10591

Re: K142758

Trade/Device Name: ADVIA® Centaur HAV Total Assay Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A virus (HAV) serological assays Regulatory Class: II Product Code: LOL Dated: September 23, 2014 Received: September 25, 2014

Dear Mr. Liu:

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. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. 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

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Stephen J. Lovell -S for

Sally A. Hojvat. M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K142758

Device Name ADVIA Centaur® HAV Total Assay

Indications for Use (Describe) ADVIA Centaur and ADVIA Centaur XP systems:

Assay performance characteristics have not been established for immunosompromised or immunosuppressed patients.

WARNING: This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

United States federal law restricts this device to sale by or on the order of a physician.

ADVIA Centaur CP system:

The ADVIA Centaur HAV Total (HAVT) assay is an in vitro diagnostic immunoassay for the qualitative deternination of total antibodies to hepatitis A virus (anti-HAV) in human neonatal, pediatric, and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur CP system. This anti-HAV assay is indicated as an aid in the diagnosis of previous or ongoing hepatitis A viral infection of HAV-susceptible individuals for vaccination.

Assay performance characteristics have not been established for immunosuppressed patients.

WARNING: This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

United States federal law restricts this device to sale by or on the order of a physician.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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510(k) Summary for the

ADVIA® Centaur Hepatitis A Total (HAVT) Assay

This 510(k) summary is being submitted in accordance with 21 CFR 807.92.

A. 510(k) Number: K142758

B. Date of Preparation: December 5, 2014

C. Proprietary and Established Names:

ADVIA® Centaur HAV Total Assay

D. Applicant:

Siemens Healthcare Diagnostics Inc., 511 Benedict Ave, Tarrytown, NY 10591 Philip Liu, Senior Manager, Requlatory Affairs and Compliance Office: (914) 524-2443 Fax: (914) 524-3579

E. Regulatory Information:

1. Regulation section: 21 CFR § 866.3310
1. Classification: Class II
1. Product Code: LOL, Hepatitis A virus (HAV) serological assays
1. Panel: Microbiology

F. Purpose of this Submission

The purpose of this submission is to add the neonate and pediatric populations to the Intended Use statement of the ADVIA Centaur HAV Total assay approved under PMA P040017.

G. Predicate Device:

The ADVIA® Centaur HAV Total Assay is substantially equivalent to the VITROS Immunodiagnostic Products Anti-HAV Total Reagent Pack cleared under 510(k) K060678.

H. Device Description:

The ADVIA Centaur HAVT reagent kit contains the following:

. ReadyPack® primary reagent pack containing ADVIA Centaur HAVT Lite Reagent, Solid Phase Reagent, and Antigen Reagent
ReadyPack ancillary pack containing ADVIA Centaur HAVT Ancillary Reagent
ADVIA Centaur HAVT Low Calibrator .
ADVIA Centaur HAVT High Calibrator ●
ADVIA Centaur systems HAVT Master Curve card

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. ADVIA Centaur systems HAVT Calibrator Assigned Value Card
The HAVT ReadyPack consists of the following:

Primary reagent pack

. The Lite Reagent is an anti-human HAV monoclonal antibody (~1.0 ug/mL) labeled with acridinium ester and biotinylated monoclonal mouse anti-HAV Fab fragment (~0.08 µg/mL) in phosphate buffer with bovine serum albumin, sodium azide (< 0.1%) and preservatives
The Solid Phase is a streptavidin coated paramagnetic microparticles in . phosphate buffer with bovine serum albumin, sodium azide (< 0.1%) and preservatives
The Antigen Reagent is HAV antigen (~0.06 µg/mL) in tricine buffer with bovine serum albumin, stabilizers, sodium azide (< 0.1%) and preservatives

Ancillary pack

The Ancillary Reagent is cysteine in citrate buffer with EDTA and preservatives .

HAVT Calibrators

Processed human plasma positive for anti-HAV antibodies with sodium azide . (< 0.1%)

I. Intended Use / Indications for Use:

ADVIA Centaur and ADVIA Centaur XP systems:

The ADVIA Centaur HAV Total (HAVT) assay is an in vitro diagnostic immunoassay for the qualitative determination of total antibodies to hepatitis A virus (anti-HAV) in human neonatal, pediatric, and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur and ADVIA Centaur XP systems. This anti-HAV assay is indicated as an aid in the diagnosis of previous or onqoing hepatitis A viral infection or in the identification of HAV-susceptible individuals for vaccination.

Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients.

WARNING: This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

United States federal law restricts this device to sale by or on the order of a physician.

ADVIA Centaur CP system:

The ADVIA Centaur HAV Total (HAVT) assay is an in vitro diagnostic immunoassay for the qualitative determination of total antibodies to hepatitis A virus (anti-HAV) in human neonatal, pediatric, and adult serum or plasma (potassium EDTA, lithium or sodium heparinized) using the ADVIA Centaur CP system. This anti-HAV assay is indicated as an aid in the diagnosis of previous or ongoing hepatitis A viral infection or in the identification of HAV-susceptible individuals for vaccination.

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Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients.

WARNING: This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

United States federal law restricts this device to sale by or on the order of a physician.

The assay is also being marketed on the ADVIA Centaur instrument family members, ADVIA Centaur XP and ADVIA Centaur CP, following FDA's Replacement Reagent and Instrument Family Policy (December 11, 2003).

J. Substantial Equivalence Information:

Both the ADVIA Centaur HAVT and the VITROS Immunodiagnostic Products Anti-HAV Total Reagent Pack (cleared under 510(k) K060678) employ the prepackaged reagents for use on automated test systems. The Intended Use / Indications for Use. Assay Principle and reagent formulations (use of mouse monoclonal antibodies) are very similar. The major differences between the Device and Predicate Devices are the standardization / traceability and the differences in conjugation of the monoclonal antibodies. A comparison of the important similarities and differences of these assays is shown in the following tables:

Assay:

Similarities:

ltem	Modified Device:ADVIA Centaur HAV Total Assay	Predicate Device:VITROS Anti-HAV Total Reagent
Intended Use	For the qualitative determination oftotal antibodies to hepatitis A virus(anti-HAV) in human neonate,pediatric, and adult samples	For the qualitative detection of totalantibody (IgG and IgM) tohepatitis A virus (total anti-HAV) inhuman adult and pediatric samples
Indications forUse	An aid in the diagnosis of previousor ongoing hepatitis A viral infectionor in the identification of HAV-susceptible individuals forvaccination	Aid in the clinical laboratorydiagnosis of individuals with acuteor past hepatitis A virus infection, oras an aid in the identification ofHAV-susceptible individuals prior toHAV vaccination. The detection ofHAV-specific antibodies in humanserum or plasma is laboratoryevidence of acute or recent HAVinfection.
Sample type	Serum and Plasma	Same
Measurement	Qualitative	Same
Assay Principle	Competitive immunoassay	Same
Technology	Chemiluminescence	Same

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Differences:

ltem	Modified Device:ADVIA Centaur HAVT Assay	Predicate Device:VITROS Anti-HAV Total Reagent
Standardization /Traceability	Assay cutoff (Index Value 1.00) isequivalent to 20 mIU/mLstandardized to the WHO 200International Standard for Anti-Hepatitis A Immunoqlobulin (97/646)	Traceable to an in-house referencecalibrator which has been valueassigned to optimize the clinicalsensitivity and specificityperformance.
DetectionAntibody	Mouse monoclonal anti-HAVantibody labeled with acridiniumester	Mouse monoclonal anti-HAVantibody labeled with horseradishperoxidase (HRP)
Capture Antibody	Fab fragment of mouse monoclonalanti-HAV antibody labeled with biotin	Mouse monoclonal anti-HAVantibody labeled with biotin

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

· None Referenced

L. Test Principle

The ADVIA Centaur HAV Total assav is a fully automated, competitive immunoassav using direct, chemiluminescent technology. The assay consists of three reagent addition and incubation steps. First, the sample is pretreated with Ancillary Reagent containing cysteine. Next, HAV antigen is added from the ancillary well (Antigen Reagent). Lite Reagent and Solid Phase are then added. The Lite Reagent contains monoclonal mouse antibody to HAV antigen labeled with acridinium ester and biotinylated Fab fragment of a monoclonal mouse antibody to HAV antigen. The Solid Phase contains streptavidin covalently coupled to paramaqnetic particles. After the final incubation, the immunocomplex formed is washed with Wash 1 prior to initiation of the chemiluminescent reaction.

M. Performance Characteristics

The following studies were performed to demonstrate that the neonate and pediatric populations can be used in the ADVIA Centaur HAV Total assay:

• Spike / recovery of anti-HAV antibodies into neonate samples

A study was conducted to evaluate the results observed when neonatal samples are tested with the ADVIA Centaur HAVT assay. Cord blood serum was used as a surrogate for neonatal serum. A total of thirty (30) cord blood and 30 adult serum samples were spiked with anti-HAV positive stock to vield samples at different analyte levels. The distribution of percent bias between the index values of the cord blood serum samples and the mean observed index values of the adult serum samples are summarized in the following table:

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Distribution of %Bias (Neonatal Cord Blood vs. Adult Serum)
Adult SpikedObserved Mean(Index)	Number Tested (n)	Distribution of % Bias	≤ 10%	> 10% to ≤ 20%	> 20% to ≤ 30%	> 30%
Negative (0.6)	6	0.0%(0/6)	33.3%(2/6)	33.3%(2/6)	33.3%(2/6)
Cut-off (1.0)	6	16.7%(1/6)	33.3%(2/6)	50.0%(3/6)	0.0%(0/6)
Low Pos. (1.7)	12	83.3%(10/12)	16.7%(2/12)	0.0%(0/12)	0.0%(0/12)
High Pos. (5.8)	6	83.3%(5/6)	16.7%(1/6)	0.0%(0/6)	0.0%(0/6)
Total:	30	53.33% (16/30)	23.33% (7/30)	16.67% (5/30)	6.67% (2/30)

Distribution of %Bias (Neonatal Cord Blood vs. Adult Serum)

• Spike / recovery of anti-HAV antibodies into pediatric samples

A study was conducted to evaluate the results observed when pediatric samples are tested with the ADVIA Centaur HAVT assay. A total of thirty (30) pediatric and 30 adult serum samples were spiked at different analyte levels. The distribution of percent bias between the index values of the spiked pediatric serum samples and the mean observed index values of the adult serum samples are summarized in the following table:

Adult SpikedObserved Mean(Index)	Number Tested (n)	≤ 10%	> 10% to ≤ 20%	> 20% to ≤ 30%	> 30%
Negative (0.6)	6	0.0%(0/6)	0.0%(0/6)	0.0%(0/6)	100.0%(6/6)
Cut-off (1.0)	6	66.7%(4/6)	16.7%(1/6)	16.7%(1/6)	0.0%(0/6)
Low Pos. (1.7)	12	50.0%(6/12)	41.7%(5/12)	0.0%(0/12)	8.3%(1/12)
High Pos. (5.8)	6	83.3%(5/6)	16.7%(1/6)	0.0%(0/6)	0.0%(0/6)
Total:	30	50% (15/30)	23.33% (7/30)	3.33% (1/30)	23.33% (7/30)

Distribution of V Rice (Dedictria va Adult Sarum)

· Concordance Study using Pediatric Samples (Clinical)

Fifty-five (55) pediatric serum samples (male and female, age range from 2 to 21 years), including samples from a high risk population, were evaluated with the ADVIA Centaur HAVT assay and another commercially available assay. The percent agreement between the assays is shown as follows:

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		Comparative anti-HAV Total Assay
		Positive	Borderline	Negative	Totals
ADVIA Centauranti-HAV Total Assay	Reactive	11	0	1	12
	Nonreactive	0	2	41	43
	Total	11	2	42	55

Results of Pediatric Population (2 - 21 years) Comparison Study

% Positive Agreement = 84.62% (11/13*)

95% Confidence Interval = 54.55 to 98.08%

% Negative Agreement = 97.62% (41/42)

95% Confidence Interval = 87.43 to 99.94%

The 2 borderline results from the comparative assay are scored as discordant results in the %Positive Agreement calculation. The ADVIA Centaur HAVT assay does not have a borderline or an equivocal zone.

The inclusion of neonate and pediatric populations in the ADVIA Centaur HAVT intended use does not necessitate the collection of additional analytical performance data since there was no change to the assay. All performance data are cross-referenced to the original Premarket Approval for the ADVIA Centaur HAVT assay on the ADVIA Centaur systems (P040017).

Specifically, the following studies are not needed for the purpose of this submission:

I Precision/Reproducibility
I Calibrator/Assay Traceability
l Calibrator/Assay Stability
l Assay Cut-off
l Method Comparison
I Matrix Comparison
I Analytical Sensitivity
l Analytical Specificity

N. Conclusions

Comparative testing of the ADVIA Centaur HAVT assay with the addition of the neonate and pediatric populations is substantially equivalent in principle and performance to the Predicate Device VITROS Immunodiagnostic Products Anti-HAV Total Reagent Pack cleared under 510(k) K060678.

Regulation Number and Section

§ 866.3310 Hepatitis A virus (HAV) serological assays.

(a)
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.(b)
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.