The ARCHITECT HAVAB-G assay is a chemiluminescent microparticle immunoassay (CMIA) for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric serum from patients with signs and symptoms or at risk for hepatitis. The ARCHITECT HAVAB-G assay is used to determine the immune status of individuals to hepatitis A virus infection.

Warning: This assay has not been FDA cleared or approved for the screening of blood or plasma donors. This assay cannot be used for the diagnosis of acute HAV infection.

Assay performance characteristics have not been established when the ARCHITECT HAVAB-G assay is used in conjunction with other hepatitis assays.

Device Description

The ARCHITECT HAVAB-G assay determines the presence of IgG anti-HAV in human serum. After an acute HAV infection, IgG anti-HAV levels rise quickly and may persist for life. The presence of IgG anti-HAV implies past HAV infection (recent or distant) or vaccination against HAV. Detectable levels above the assay cut-off suggest immunity to HAV infection. The ARCHITECT HAVAB-G assay is a two-step immunoassay for the qualitative detection of IgG anti-HAV in human serum using CMIA technology with flexible assay protocols, referred to as Chemiflex. In the first step, sample, assay diluent, and hepatitis A virus (human) coated paramagnetic microparticles are combined. IgG anti-HAV present in the sample binds to the hepatitis A virus (human) coated microparticles. After washing, the anti-human IgG acridinium-labeled conjugate that is added in the second step binds to IgG anti-HAV. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). The presence or absence of IgG anti-HAV in the sample is determined by comparing the chemiluminescent signal in the reaction to the cutoff signal determined from an ARCHITECT HAVAB-G calibration. Specimens with signal to cutoff (S/CO) values > 1.00 are considered reactive for IgG anti-HAV. Specimens with S/CO values < 1.00 are considered nonreactive.

AI/ML Overview

The provided document describes the ARCHITECT HAVAB-G assay, a device for qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV). The study demonstrates its performance relative to existing assays, ARCHITECT HAVAB-M and AxSYM HAVAB 2.0, to establish substantial equivalence.

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a numerical or percentage format. Instead, the performance is presented as Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a "HAV IgG Final Status as determined by ARCHITECT HAVAB-M and AxSYM HAVAB 2.0 assays." The implicit acceptance criterion is that these agreement rates should be sufficiently high to demonstrate substantial equivalence to the predicate devices.

Population	Positive Percent Agreement (PPA)	95% Confidence Interval (PPA)	Negative Percent Agreement (NPA)	95% Confidence Interval (NPA)
Increased risk	94.49% (120/127)	88.97% - 97.76%	100.00% (133/133)	97.26% - 100.00%
Signs and symptoms	95.67% (265/277)	92.55% - 97.74%	96.64% (230/238)	93.48% - 98.54%
Vaccine Recipients	100.00% (48/48)	92.60% - 100.00%	100.00% (2/2)	15.81% - 100.00%
Surplus pediatric population #1	83.33% (10/12)	51.59% - 97.91%	97.96% (96/98)	92.82% - 99.75%
Surplus pediatric population #2	100.00% (72/72)	95.01% - 100.00%	97.69% (127/130)	93.40% - 99.52%
Surplus pediatric population total	97.62% (82/84)	91.66% - 99.71%	97.81% (223/228)	94.96% - 99.28%
Prospective pediatric population	66.67% (2/3)	9.43% - 99.16%	100.00% (20/20)	83.16% - 100.00%

The broad 95% confidence intervals for small sample sizes (e.g., Vaccine Recipients NPA, Prospective pediatric population PPA) indicate less certainty for those specific subgroups, but the overall high agreement percentages across several populations likely met the internal criteria for substantial equivalence.

2. Sample size used for the test set and the data provenance:

Sample Size: A total of 1147 specimens were used for the clinical performance evaluation.
Data Provenance: Specimens were obtained from collection centers and vendors in the United States. The study appears to be retrospective for most populations (e.g., "Surplus pediatric population") and potentially prospective for specific groups ("Prospective pediatric population"). The overall nature is a collection of previously acquired samples and some prospectively collected ones.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

The document does not specify the number of experts or their qualifications for establishing the ground truth. It states that the ground truth ("HAV IgG Final Status") was "determined by ARCHITECT HAVAB-M and AxSYM HAVAB 2.0 assays." These are established diagnostic assays, implying that their results are considered the reference standard, not a subjective interpretation by human experts.

4. Adjudication method for the test set:

Not applicable. The ground truth was established by the results of two predicate assays, ARCHITECT HAVAB-M and AxSYM HAVAB 2.0, not through human adjudication of differing interpretations.

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:

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an automated immunoassay for detecting antibodies, not an AI or imaging-based device requiring human reader interpretation or assistance.

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

Yes, the study presents the performance of the ARCHITECT HAVAB-G assay as a standalone algorithm (the CMIA technology is an automated process). The assay determines the presence or absence of IgG anti-HAV by comparing the chemiluminescent signal to a cutoff. There is no human interpretation or interaction required for the performance results tabulated.

7. The type of ground truth used:

The ground truth was established by the results of two reference diagnostic assays: ARCHITECT HAVAB-M and AxSYM HAVAB 2.0 assays. This is a form of comparative assay reference, where the device under evaluation is compared against an accepted method for determining the presence or absence of the target analyte.

8. The sample size for the training set:

The document does not specify a separate "training set" sample size. The studies listed (e.g., Assay Cut-Off Determination, Within-Laboratory Precision) describe analytical performance evaluations that would contribute to the assay's development and optimization, rather than a distinct 'training set' in the context of machine learning. For an immunoassay, the "training" involves setting assay parameters and cutoffs, which is typically done using various panels of known positive and negative samples, but these are not explicitly quantified as a "training set" in this type of submission.

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

Not explicitly detailed as a separate "training set" with ground truth in the document. For immunoassays, the ground truth for establishing parameters like the assay cutoff would typically involve using panels of well-characterized clinical samples (e.g., confirmed positive for HAV IgG, confirmed negative for HAV IgG) to establish appropriate thresholds for distinguishing positive from negative results. The "Assay Cut-Off Determination" study listed would be the primary mechanism for this.

Summary

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K//13704

JUN 2 8 2012

510(k) Summary

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Applicant Name:

Abbott Laboratories Diagnostics Division Dept. 9V6. AP5N-2 100 Abbott Park Road Abbott Park, IL 60064

Contact person for all communications:

Judith Wallach, ADD, Regulatory Affairs Project Manager . Phone (847) 937-1132 Fax (847) 937-4836 E-Mail judith.r.wallach@abbott.com
or
Grace LeMieux, ADD, Regulatory Affairs Director . Phone (847) 935-0409 Fax (847) 937-4836 E-mail grace.lemieux@abbott.com

Device Name:

Reagent Kit

Classification Name: Hepatitis A virus (HAV) serological assays Trade Name: ARCHITECT HAVAB-G (List No. 6L27) Common Name: Hepatitis A Test (IgG Antibody) Governing Regulation: 866.3310 Device Classification: II Classification Panel: Microbiology Code: LOL

Calibrator Kit Classification Name: Calibrator Trade Name: ARCHITECT HAVAB-G Calibrator Kit (List No. 6L27-01) Common Name: Calibrator Governing Regulation: 862.1150 Device Classification: II Classification Panel: Clinical Chemistry Code: JIS

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Control Kit

Classification Name: Quality control material (assayed and unassayed) Trade Name: ARCHITECT HAVAB-G Control Kit (List No. 6L27-10) Common Name: Control Governing Regulation: 862.1660 Device Classification: I Classification Panel: Microbiology Code: MJY/MJX

Legally marketed device to which equivalency is claimed:

ARCHITECT HAVAB-M (K063329)

FDA Document Numbers of all prior related submissions (regardless of outcome): ARCHITECT HAVAB-G Pre-IDE I00394

Intended Use of Device:

Warning: This assay has not been FDA cleared or approved for the screening of blood or plasma donors. This assay cannot be used for the diagnosis of acute HAV infection.

Device Description:

The ARCHITECT HAVAB-G assay determines.the presence of IgG anti-HAV in human serum. After an acute HAV infection, IgG anti-HAV levels rise quickly and may persist for life. The presence of IgG anti-HAV implies past HAV infection (recent or distant) or vaccination against HAV. Detectable levels above the assay cut-off suggest immunity to HAV infection. 1.2

The ARCHITECT HAVAB-G assay is a two-step immunoassay for the qualitative detection of IgG anti-HAV in human serum using CMIA technology with flexible assay protocols, referred to as Chemiflex.

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In the first step, sample, assay diluent, and hepatitis A virus (human) coated paramagnetic microparticles are combined. IgG anti-HAV present in the sample binds to the hepatitis A virus (human) coated microparticles. After washing, the anti-human IgG acridinium-labeled conjugate that is added in the second step binds to IgG anti-HAV. Following another wash cycle, pre-trigger and trigger solutions are added to the reaction mixture. The resulting chemiluminescent reaction is measured as relative light units (RLUs). The presence or absence of IgG anti-HAV in the sample is determined by comparing the chemiluminescent signal in the reaction to the cutoff signal determined from an ARCHITECT HAVAB-G calibration. Specimens with signal to cutoff (S/CO) values

1.00 are considered reactive for IgG anti-HAV. Specimens with S/CO values < 1.00 are considered nonreactive.

Comparison of Technological Characteristics:

The ARCHITECT HAVAB-G assay utilizes chemiluminescent microparticle immunoassay (CMIA) technology for the qualitative detection of IgG anti-HAV in human adult and pediatric serum. The ARCHITECT HAVAB-M assay utilizes chemiluminescent microparticle immunoassay (CMIA) technology for the qualitative detection of IgM anti-HAV in human serum and plasma.

The analytical performance of the ARCHITECT HAVAB-G assay was demonstrated through the following studies:

· · Assay Cut-Off Determination
. Tube Type
Sample Stability .
Sample On-Board Stability .
Within-Laboratory Precision (20-Day Precision) .
. Analytical Specificity (Other Disease States)
Interferences Bilirubin, Hemoglobin, Protein, and Triglycerides .
Seroconversion Detection .
. High Dose Hook Effect
Reagent On-Board Drift .
Within-Assay Sample Carryover .

ARCHITECT HAVAB-G 510(k) December 2011

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Summary of Clinical Performance:

A total of 1147 specimens were obtained from collection centers and vendors in the United States and distributed among the three clinical centers to evaluate the performance of the ARCHITECT HAVAB-G compared to the HAV IgG Final Status as determined by ARCHITECT HAVAB-M and AxSYM HAVAB 2.0 assays. The following populations were studied: Individuals at increased risk of HAV infection, individuals with signs and symptoms of hepatitis, hepatitis A vaccine recipients, and surplus specimens from a pediatric population. The results are summarized in the table below.

Populations	Positive Percent Agreement(PPA)		Negative Percent Agreement(NPA)
	PPA	95%ConfidenceInterval	NPA	95%ConfidenceInterval
Increased risk	94.49 (120/127)	88.97-97.76	100.00 (133/133)	97.26-100.00
Signs andsymptoms	95.67 (265/277)	92.55-97.74	96.64 (230/238)	93.48-98.54
VaccineRecipients	100.00 (48/48)	92.60-100.00	100.00 (2/2)	15.81-100.00
Surplus pediatricpopulation #1	83.33 (10/12)	51.59-97.91	97.96 (96/98)	92.82-99.75
Surplus pediatricpopulation #2	100.00 (72/72)	95.01-100.00	97.69 (127/130)	93.40-99.52
Surplus pediatricpopulation total	97.62 (82/84)	91.66-99.71	97.81 (223/228)	94.96-99.28
Prospectivepediatricpopulation	66.67% (2/3)	9.43-99.16	100.00 (20/20)	83.16-100.00

Conclusions:

The results of the clinical performance studies, as determined by ARCHITECT HAVAB-M and AxSYM HAVAB 2.0 assays, and the analytical studies demonstrate that the ARCHITECT HAVAB-G assay is substantially equivalent to the ARCHITECT HAVAB-M assay.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of several curved lines.

Food and Drug Administration

10903 New Hampshire Avenue Silver Spring, MD 20993

Abbott Laboratories, Inc. c/o Ms. Judith Wallach 100 Abbott Park Road Dept. 09V6 AP5 North Abbott Park, Illinois 60064-6095

JUN 2 8 2012

Re: K113704

Trade/Device Name: ARCHITECT HAVAB-G ARCHITECT HAVAG-G Calibrator ARCHITECT HAVAG-G Controls Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A virus (HAV) serological assays Regulatory Class: Class II Product Code: LOL, MJY, MJX, JIS Dated: May 18, 2012 Received: May 18, 2012

Dear Ms. Wallach:

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.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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

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Page 2 - Ms. Judith Wallach .

CFR Part 807): labeling (21 CFR Parts 801 and 809): medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Freddie W. Poole
air

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

Enclosure

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Indications for Use Statement

510(k) Number (if known): K113704

Device Name: ARCHITECT HAVAB-G

ARCHITECT HAVAB-G Calibrator

ARCHITECT HAVAB-G Controls

Indications for Use:

ARCHITECT HAVAB-G

Warning: This assay has not been FDA cleared or approved for the screening of blood or plasma donors. This assay cannot be used for the diagnosis of acute HAV infection.

Assay performance characteristics have not been established when the ARCHITECT HAVAB-G assay is used in conjunction with other hepatitis assays.

ARCHITECT HAVAB-G Calibrator:

The ARCHITECT HAVAB-G Calibrator is for the calibration of the ARCHITECT i System, when used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric serum from patients with signs and symptoms or at risk for hepatitis. The ARCHITECT HAVAB-G assay is used to determine the immune status of individuals to hepatitis A virus infection, using the ARCHITECT HAVAB-G Reagent Kit. The performance of the ARCHITECT HAVAB-G Calibrator has not been established with any other IgG anti-HAV assays.

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HAVAB-G Controls:

The ARCHITECT HAVAB-G Controls are used for monitoring the performance of the ARCHITECT i System, when used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric serum from patients with signs and symptoms or at risk for hepatitis. The ARCHITECT HAVAB-G assay is used to determine the immune status of individuals to hepatitis A virus infection, using the ARCHITECT HAVAB-G Reagent Kit. The performance of the ARCHITECT HAVAB-G Controls have not been established with any other IgG anti-HAV assays

Prescription Use X (Part 21 CFR 801 Subpart D) And/Or

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Tauray V. Feldbok

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) Kil 3704

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.