(323 days)
ARCHITECT HAVAB-G (-K113704)
Not Found
No
The summary describes a standard immunoassay for detecting antibodies and does not mention any AI/ML components or methodologies.
No
This device is an in vitro diagnostic test used to detect antibodies to the hepatitis A virus, which helps determine immune status. It does not provide any therapeutic intervention.
Yes
The device is used for the qualitative detection of IgG antibody to hepatitis A virus, which determines the immune status of individuals to HAV infection. This falls under the definition of a diagnostic device as it provides information for diagnosis, even though it cannot be used for the diagnosis of acute HAV infection.
No
The device description explicitly states it is a chemiluminescent microparticle immunoassay (CMIA) and includes reagents (Microparticles, Conjugate, Assay Diluent), Calibrator, and Controls, which are physical components, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the assay is used for the "qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric... serum and plasma". This involves testing biological samples (serum and plasma) in vitro (outside the body) to obtain diagnostic information about a patient's immune status to HAV infection.
- Device Description: The description confirms it's a "chemiluminescent microparticle immunoassay (CMIA)" used for detecting an analyte (IgG anti-HAV) in human samples. It also lists the components of the kit, which are reagents used for laboratory testing.
- Performance Studies: The performance studies describe testing the assay with human serum and plasma samples to evaluate its accuracy and reliability in detecting the target analyte.
All of these characteristics align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system.
The HAVAb IgG II assay is used to determine the immune status of individuals to hepatitis A virus (HAV) infection. Warning: This assay has not been cleared for use in screening blood, plasma, or tissue donors. This assay cannot be used for the diagnosis of acute HAV infection.
Assay performance characteristics have not been established when the HAVAb IgG II assay is used in conjunction with other hepatitis assays.
Product codes (comma separated list FDA assigned to the subject device)
LOL, JIS, QCH
Device Description
The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMIA) for the qualitative detection of IgG anti-HAV. The kit consists of reagents, calibrators, and controls.
Reagents:
- Microparticles: HAV (human) coated microparticles in MOPS / potassium chloride buffer. Minimum concentration: 0.08% solids. Preservative: ProClin 300.
- Conjugate: Anti-human IgG (mouse, monoclonal) acridinium-labeled conjugate in MES / sodium chloride buffer with protein (bovine) stabilizer and surfactants. Minimum concentration: 0.01 µg/mL. Preservatives: ProClin 300 and ProClin 950.
- Assay Diluent: Assay diluent containing protein (goat, mouse, and bovine) stabilizers in TRIS buffer and surfactant. Preservatives: ProClin 300 and ProClin 950.
Calibrator:
- Calibrator 1 contains recalcified human plasma reactive for IgG antibody to hepatitis A virus (IgG anti-HAV), with preservatives ProClin 300 and sodium azide. Target concentration: 50.0 mIU/mL. It is traceable to the WHO 2nd International Standard for Anti-hepatitis A, Immunoglobulin, Human (NIBSC Code: 97/646).
Controls:
- Negative control contains recalcified anti-HAV negative human plasma with protein (bovine) stabilizer.
- Positive control contains recalcified human plasma reactive for IgG anti-HAV.
Both controls contain preservatives ProClin 300 and sodium azide. The positive control is traceable to the WHO 2nd International Standard for Anti-hepatitis A, Immunoglobulin, Human (NIBSC code: 97/646).
Biological Principles of the Procedure:
This is an automated, two-step immunoassay. Sample, HAV (human) coated paramagnetic microparticles, and assay diluent are combined and incubated. IgG anti-HAV in the sample binds to the microparticles. The mixture is washed. Anti-human IgG acridinium-labeled conjugate is added and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added. The resulting chemiluminescent reaction is measured as a relative light unit (RLU). The amount of IgG anti-HAV in the sample is directly related to the RLU. The presence or absence of IgG anti-HAV is determined by comparing the RLU to a cutoff RLU from an active calibration.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Adult and pediatric (4 through 21 years)
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Summary of Performance Studies:
Clinical Performance - Expected Values:
Sample Size: 519 specimens from apparently healthy individuals, 250 specimens from individuals at increased risk of HAV infection, 499 specimens from individuals with signs and symptoms of hepatitis infection, and 105 specimens from the pediatric population.
Data Source:
- Apparently healthy population: collected from multiple sites in Texas, Wisconsin, and New York.
- Adults at increased risk of HAV infection: collected in California, Colorado, Florida, Illinois, Massachusetts, North Carolina, and Texas.
- Adults with signs and symptoms of hepatitis infection: collected in California, Colorado, Florida, Illinois, Massachusetts, and Texas.
- Pediatric population: collected in the US (California and Massachusetts) and Belgium.
Annotation Protocol: Expected values based on the distribution of reactive and nonreactive results observed in these populations.
Analytical Specificity - Potentially Interfering Substances:
Study performed based on guidance from CLSI EP07, 3rd ed. Each substance tested at 2 levels of the analyte (approximately 0.80 S/CO and 1.20 S/CO).
Analytical Specificity - Other Specimen Conditions or Disease States:
Sample Size: 251 specimens from 21 different categories of individuals with medical conditions unrelated to HAV.
Annotation Protocol: All specimens tested nonreactive for IgG anti-HAV as determined by a comparator assay (ARCHITECT HAVAB-G).
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Within-Laboratory Precision (20-Day)
Study type: Precision study (based on CLSI EP05-A3)
Sample size: Not explicitly stated for each sample, but 80 runs were performed for each of 4 samples/controls.
Key results:
- High Negative Panel 1: Mean (S/CO) 0.71, Within-Run SD 0.025, Within-Laboratory SD 0.028 (range 0.026-0.045)
- Low Positive Panel 2: Mean (S/CO) 1.25, Within-Run SD 0.040 (%CV 3.2), Within-Laboratory SD 0.040 (range 0.036-0.078) (%CV 3.2, range 2.9-5.8)
- Negative Control: Mean (S/CO) 0.09, Within-Run SD 0.011, Within-Laboratory SD 0.015 (range 0.011-0.035)
- Positive Control: Mean (S/CO) 2.19, Within-Run SD 0.053 (%CV 2.4), Within-Laboratory SD 0.063 (range 0.055-0.090) (%CV 2.9, range 2.5-4.0)
Analytical Specificity - Potentially Interfering Substances
Study type: Interference testing (based on CLSI EP07, 3rd ed.)
Sample size: Not explicitly stated for each substance.
Key results: No significant interference (interference ≤ +0.10 S/CO for 0.80 S/CO samples and > -10% for 1.20 S/CO samples) was observed at specified concentrations for Bilirubin (Conjugated), Bilirubin (Unconjugated), Biotin, Hemoglobin, Total Protein, and Triglycerides.
Analytical Specificity - Other Specimen Conditions or Disease States
Study type: Specificity evaluation
Sample size: 251 specimens from 21 different categories.
Key results: 241 specimens (96.02%) were nonreactive and 10 specimens (3.98%) were reactive by the HAVAb IgG II assay among specimens from individuals with medical conditions unrelated to HAV that were nonreactive by a comparator assay (ARCHITECT HAVAB-G).
Expected Values
Study type: Clinical performance evaluation
Sample size: Total of 519 apparently healthy individuals, 250 individuals at increased risk of HAV infection, 499 individuals with signs and symptoms of hepatitis infection, and 105 pediatric samples.
Key results: Presented as percentages of reactive and nonreactive results within each population:
- Apparently Healthy Adults (High Prevalence Area for HAV): Reactive 34.46%, Nonreactive 65.54%
- Apparently Healthy Adults (Low Prevalence Area for HAV): Reactive 24.87%, Nonreactive 75.13%
- Apparently Healthy Pediatrics (High Prevalence Area for HAV): Reactive 13.33%, Nonreactive 86.67%
- Apparently Healthy Pediatrics (Low Prevalence Area for HAV): Reactive 13.33%, Nonreactive 86.67%
- Increased Risk of HAV Infection: Reactive 49.19%, Nonreactive 50.81%
- Signs and Symptoms of Hepatitis Infection: Reactive 60.17%, Nonreactive 39.83%
- Pediatric Population: Reactive 86.67%, Nonreactive 13.33%
- For 21 pediatric specimens (4 from increased risk, 17 from signs/symptoms): 9.52% reactive, 90.48% nonreactive.
System Reproducibility
Study type: Reproducibility study (based on CLSI EP05-A3)
Sample size: 360 for each sample/control tested across 3 sites.
Key results:
- High Negative Panel A: Mean (S/CO) 0.66, Repeatability SD 0.037, Within-Laboratory SD 0.042, Reproducibility SD 0.053
- Low Positive Panel B: Mean (S/CO) 1.32, Repeatability SD 0.044 (%CV 3.4), Within-Laboratory SD 0.056 (%CV 4.3), Reproducibility SD 0.069 (%CV 5.2)
- Negative Control: Mean (S/CO) 0.11, Repeatability SD 0.039, Within-Laboratory SD 0.042, Reproducibility SD 0.046
- Positive Control: Mean (S/CO) 2.26, Repeatability SD 0.066 (%CV 2.9), Within-Laboratory SD 0.088 (%CV 3.9), Reproducibility SD 0.106 (%CV 4.7)
Percent Agreement
Study type: Prospective multi-center study comparing HAVAb IgG II to ARCHITECT HAVAB-G.
Sample size:
- Individuals at Increased Risk of HAV Infection: n=250
- Individuals with Signs and Symptoms of Hepatitis Infection: n=499
- Pediatric Population: n=105
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Percent Agreement
- Individuals at Increased Risk of HAV Infection:
- PPA (Positive Percent Agreement): 96.75% (119/123), 95% CI (91.94%, 98.73%)
- NPA (Negative Percent Agreement): 98.43% (125/127), 95% CI (94.44%, 99.57%)
- Individuals with Signs and Symptoms of Hepatitis Infection:
- PPA: 95.39% (290/304), 95% CI (92.42%, 97.24%)
- NPA: 98.97% (193/195), 95% CI (96.34%, 99.72%)
- Pediatric Population:
- PPA: 100.00% (90/90), 95% CI (95.91%, 100.00%)
- NPA: 93.33% (14/15), 95% CI (70.18%, 98.81%)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
ARCHITECT HAVAB-G (-K113704)
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
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Image /page/0/Picture/0 description: The image shows the date August 10, 2023. The text is written in a clear, serif font. The date is presented in a standard format, with the month, day, and year clearly indicated. The text is left-aligned.
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Abbott Laboratories Dominic Tunzi Regulatory Project Manager 100 Abbott Park Road Abbott Park, Illinois 60064
Re: K222850
Trade/Device Name: HAVAb IgG II Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A Virus (HAV) Serological Assays Regulatory Class: Class II Product Code: LOL Dated: September 19, 2022 Received: September 21, 2022
Dear Dominic Tunzi:
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
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 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 (OS) 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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Maria I. Garcia -S
Maria Garcia, Ph.D. Assistant Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K222850
Device Name HAVAb IgG II
Indications for Use (Describe)
The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system.
The HAVAb IgG II assay is used to determine the immune status of individuals to hepatitis A virus (HAV) infection. Warning: This assay has not been cleared for use in screening blood, plasma, or tissue donors. This assay camot be used for the diagnosis of acute HAV infection.
Assay performance characteristics have not been established when the HAVAb IgG II assay is used in conjunction with other hepatitis assays.
| 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
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.
I. 510(k) Number
K22850
II. Applicant Name
Abbott Laboratories Department 09AA, Building CP01 100 Abbott Park Road Abbott Park, IL 60064
Primary contact person for all communications:
Dominic Tunzi, Regulatory Affairs Project Manager Abbott Laboratories dominic.tunzi(@abbott.com Phone (224) 668-3644 Fax (224) 667-4836
Secondary contact person for all communications:
Noah Lermer PhD, Director Regulatory Affairs Abbott Laboratories noah.lermer(@abbott.com Phone (224) 668-7613 Fax (224) 667-1221
Date Summary Prepared: August 9, 2023
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III. Device Name
HAVAb IgG II
Reagent
Trade Name: HAVAb IgG II Reagent Kit Device Classification: Class II Classification Name: Hepatitis A virus (HAV) serological assays Governing Regulation: 21 CFR § 866.3310 Code: LOL
Calibrator
Trade Name: HAVAb IgG II Calibrator Device Classification: Class II Classification Name: Clinical Chemistry Test Systems: Calibrator Governing Regulation: 21 CFR § 862.1150 Code: JIS
Controls
Trade Name: HAVAb IgG II Controls Device Classification: Class II Classification Name: Assayed quality control material for clinical microbiology assays Governing Regulation: 21 CFR § 866.3920 Code: QCH
IV. Predicate Device
Abbott Laboratories: ARCHITECT HAVAB-G (-K113704)
V. Description of Device
A. Reagents
The kit configuration of the HAVAb IgG II reagent kit is described below.
| Tests per cartridge | 100 |
|---|---|
| Number of cartridges per kit | 2 |
| Tests per kit | 200 |
| Microparticles | 6.6 mL |
| Conjugate | 26.5 mL |
| Assay Diluent | 10.4 mL |
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| | Microparticles: HAV (human) coated microparticles in MOPS / potassium chloride
buffer. Minimum concentration: 0.08% solids. Preservative:
ProClin 300. |
|----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Conjugate: | Anti-human IgG (mouse, monoclonal) acridinium-labeled conjugate
in MES / sodium chloride buffer with protein (bovine) stabilizer and
surfactants. Minimum concentration: 0.01 µg/mL. Preservatives:
ProClin 300 and ProClin 950. |
| Assay Diluent: | Assay diluent containing protein (goat, mouse, and bovine)
stabilizers in TRIS buffer and surfactant. Preservatives: ProClin 300
and ProClin 950. |
B. Calibrator
The HAVAb IgG II Calibrator is described below.
Calibrator 1 contains recalcified human plasma reactive for IgG antibody to hepatitis A virus (IgG anti-HAV). Preservatives: ProClin 300 and sodium azide.
The target concentration for the calibrator is provided in the following table.
| Calibrator | Quantity | Color | IgG Anti-HAV
Concentration
(mIU/mL) |
|--------------|------------|--------|-------------------------------------------|
| Calibrator 1 | 1 x 3.0 mL | Greenᵃ | 50.0 |
a Dye: Green (Acid Yellow No. 23 and Acid Blue No. 9)
The HAVAb IgG II Calibrator is traceable to the World Health Organization (WHO) 2nd International Standard for Anti-hepatitis A, Immunoglobulin, Human (NIBSC Code: 97/646).
C. Controls
The HAVAb IgG II Controls are described below.
- . The negative control contains recalcified anti-HAV negative human plasma with protein (bovine) stabilizer.
- . The positive control contains recalcified human plasma reactive for IgG anti-HAV.
Preservatives: ProClin 300 and sodium azide.
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| Control | Quantity | Color | IgG Anti-HAV
Range
(S/CO) |
|------------------|------------|---------|---------------------------------|
| Negative Control | 3 x 3.0 mL | Natural | $ \leq 0.56 $ |
| Positive Control | 3 x 3.0 mL | Blueb | 1.03 - 3.53 |
The target ranges for the controls are provided in the table below. The ranges may be used for individual replicate control specifications on the Alinity i system.
b Dye: Acid Blue No. 9
The HAVAb IgG II positive control is traceable to the WHO 2nd International Standard for Anti-hepatitis A, Immunoglobulin, Human (NIBSC code: 97/646).
D. Biological Principles of the Procedure
This assay is an automated, two-step immunoassay for the qualitative detection of IgG anti-HAV in human adult and pediatric serum and plasma from patients with signs and symptoms or at risk for hepatitis using chemiluminescent microparticle immunoassay (CMIA) technology.
Sample, HAV (human) coated paramagnetic microparticles, and assay diluent are combined and incubated. The IgG anti-HAV present in the sample binds to the HAV (human) coated microparticles. The mixture is washed. Anti-human IgG acridinium-labeled conjugate is added to create a reaction mixture and incubated. Following a wash cycle, Pre-Trigger and Trigger Solutions are added.
The resulting chemiluminescent reaction is measured as a relative light unit (RLU). There is a direct relationship between the amount of IgG anti-HAV in the sample and the RLU detected by the system optics.
The presence or absence of IgG anti-HAV in the sample is determined by comparing the chemiluminescent RLU in the reaction to the cutoff RLU determined from an active calibration.
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VI. Intended Use of the Device
The HAVAb IgG II assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV) in human adult and pediatric (4 through 21 years) serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin separin separator, dipotassium EDTA, and tripotassium EDTA tubes) from patients with signs and symptoms or at risk for hepatitis A on the Alinity i system.
The HAVAb IgG II assay is used to determine the immune status of individuals to hepatitis A virus (HAV) infection.
Warning: This assay has not been cleared for use in screening blood, plasma, or tissue donors. This assay cannot be used for the diagnosis of acute HAV infection.
Assay performance characteristics have not been established when the HAVAb IgG II assay is used in conjunction with other hepatitis assays.
VII. Comparison of Technological Characteristics
The HAVAb IgG II assay (subject device) is an automated immunoassay for the qualitative detection of IgG anti-HAV in human adult and pediatric serum and plasma from patients with signs and symptoms or at risk for hepatitis using CMIA technology on the Alinity i system.
The similarities and differences between the subject device and the predicate device are presented in the following table.
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| Similarities and Differences Between Subject & Predicate Device | ||
|---|---|---|
| Subject Device: | ||
| HAVAb IgG II | Predicate Device: | |
| ARCHITECT HAVAB-G (K113704) | ||
| General Device Characteristic Similarities | ||
| Intended Use and | ||
| Indications for Use | The HAVAb IgG II assay is a | |
| chemiluminescent microparticle | ||
| immunoassay (CMIA) used for the | ||
| qualitative detection of IgG antibody to | ||
| hepatitis A virus (IgG anti-HAV) in | ||
| human adult and pediatric (4 through | ||
| 21 years) serum (collected in serum | ||
| and serum separator tubes) and plasma | ||
| (collected in sodium heparin, lithium | ||
| heparin, lithium heparin separator, | ||
| dipotassium EDTA, and tripotassium | ||
| EDTA tubes) from patients with signs | ||
| and symptoms or at risk for hepatitis A | ||
| on the Alinity i system. | ||
| The HAVAb IgG II assay is used to | ||
| determine the immune status of | ||
| individuals to hepatitis A virus (HAV) | ||
| infection. | ||
| Warning: This assay has not been | ||
| cleared for use in screening blood, | ||
| plasma, or tissue donors. This assay | ||
| cannot be used for the diagnosis of | ||
| acute HAV infection. | ||
| Assay performance characteristics have | ||
| not been established when the HAVAb | ||
| IgG II assay is used in conjunction | ||
| with other hepatitis assays. | 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. | ||
| Methodology | Chemiluminescent Microparticle | |
| Immunoassay | Chemiluminescent Microparticle | |
| Immunoassay | ||
| Antigen Used | HAV (Strain pHM175) | HAV (Strain pHM175) |
| Interpretation of | ||
| Results | Nonreactive: * Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014. |
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B. Analytical Specificity
Potentially Interfering Substances
A study was performed based on guidance from CLSI EP07, 3rd ed. * Each substance was tested at 2 levels of the analyte (approximately 0.80 S/CO and 1.20 S/CO).
No significant interference (interference ≤ +0.10 S/CO for 0.80 S/CO samples and > -10% for 1.20 S/CO samples) was observed at the following concentrations.
| No Significant Interference | ||
|---|---|---|
| Interferent Level | ||
| Potentially Interfering Substance | Default Units | Alternate Units |
| Bilirubin (Conjugated) | 40 mg/dL | 475 $\mu$ mol/L |
| Bilirubin (Unconjugated) | 40 mg/dL | 684 $\mu$ mol/L |
| Biotin | 3600 ng/mL |
|
| Hemoglobin | 1000 mg/dL | 10 g/L |
| Total Protein | 15 g/dL | 150 g/L |
| Triglycerides | 1500 mg/dL | 16.94 mmol/L |
Other Specimen Conditions or Disease States
The HAVAb IgG II assay was evaluated for potential interference using specimens from individuals with medical conditions unrelated to HAV. All specimens tested nonreactive for IgG anti-HAV as determined by a comparator assay (ARCHITECT HAVAB-G). A total of 251 specimens from 21 different categories were evaluated; 241 specimens (96.02%) were nonreactive and 10 specimens (3.98%) were reactive by the HAVAb IgG II assay.
" Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
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| Category | n | HAVAb IgG II (on Alinity i) | |
|---|---|---|---|
| Reactive | Nonreactive | ||
| Anti-cytomegalovirus (anti-CMV) | 15 | 1 | 14 |
| Anti-Epstein-Barr virus (anti-EBV) | 11 | 0 | 11 |
| Anti-Escherichia coli (anti-E coli) | 4 | 1 | 3 |
| Anti-hepatitis B virus (anti-HBV) | |||
| (i.e., anti-HBc, anti-HBs, and HBsAg) | 24 | 2 | 22 |
| Anti-hepatitis C virus (anti-HCV) | 13 | 0 | 13 |
| Anti-mumps virus | 12 | 0 | 12 |
| Anti-nuclear antibodies (ANA) | 13 | 0 | 13 |
| Anti-rubeola (measles) virus | 14 | 0 | 14 |
| Anti-Toxoplasma gondii (anti-T gondii) | 20 | 2 | 18 |
| Anti-varicella zoster virus (anti-VZV) | 12 | 0 | 12 |
| Human anti-mouse antibodies (HAMA) | 9 | 0 | 9 |
| Hemodialysis patients | 2 | 1 | 1 |
| Hepatitis (noninfectious; chronic or acute toxic) | 10 | 0 | 10 |
| Heterophile antibodies (nonspecific) | 5 | 0 | 5 |
| Hyper IgG (monoclonal) | 14 | 2 | 12 |
| Hyper IgM (monoclonal) | 6 | 0 | 6 |
| Hyper IgM (polyclonal) | 3 | 0 | 3 |
| Influenza vaccine recipients | 12 | 0 | 12 |
| Lupus | 10 | 0 | 10 |
| Multiparous pregnant women (all trimesters) | 32 | 1 | 31 |
| Rheumatoid factor (RF) | 10 | 0 | 10 |
| Total | 251 | 10 | 241 |
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IX. Summary of Clinical Performance
A. Expected Values
Studies were performed with the HAVAb IgG II assay on the Alinity i instrument that included a total of 519 specimens from apparently healthy individuals, 250 specimens from individuals at increased risk of HAV infection, 499 specimens from individuals with signs and symptoms of hepatitis infection, and 105 specimens from the pediatric population.
The specimens from the apparently healthy population were collected from multiple sites in Texas, Wisconsin, and New York. The specimens from adults at increased risk of HAV infection were collected in California, Colorado, Florida, Illinois, Massachusetts, North Carolina, and Texas. The specimens from adults with signs and symptoms of hepatitis infection were collected in California, Colorado, Florida, Illinois, Massachusetts, and Texas. The specimens from the pediatric population were collected in the US (California and Massachusetts) and Belgium. The distribution of reactive and nonreactive results are presented in the table below.
| Apparently Healthy | | | | | Increased
Risk of
HAV
Infection | Signs and
Symptoms
of
Hepatitis
Infection | Pediatric
Population |
|--------------------|------------------------------------------|-----------------------------------------|------------------------------------------|-----------------------------------------|------------------------------------------|-------------------------------------------------------|-------------------------|
| Adults | | Pediatrics | | | | | |
| | High
Prevalence
Area(s)
for HAV | Low
Prevalence
Area(s)
for HAV | High
Prevalence
Area(s)
for HAV | Low
Prevalence
Area(s)
for HAV | | | |
| Reactive
(%) | 34.46 | 24.87 | 13.33 | 13.33 | 49.19 | 60.17 | 86.67 |
| Nonreactive
(%) | 65.54 | 75.13 | 86.67 | 86.67 | 50.81 | 39.83 | 13.33 |
In addition, 4 of the 250 specimens collected from individuals at increased risk of HAV infection and 17 of the 499 specimens from individuals with signs and symptoms of hepatitis infection were from pediatric subjects. Of the 21 specimens, 9.52% were reactive and 90.48% were nonreactive.
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B. System Reproducibility
A study was performed based on guidance from CLSI EP05-A3. Testing was conducted at each of 3 testing sites using 3 lots of the HAVAb IgG II reagents, 2 lots of the HAVAb IgG II Calibrator, 2 lots of the HAVAb IgG II Controls, and 1 instrument. Two controls and 2 human serum panels were tested in replicates of 4 at 2 separate times per day on 5 different days.
| Sample | n | Mean
(S/CO) | Repeatability | | Within-Laboratorya | | Reproducibilityb | |
|--------------------------|-----|----------------|---------------|-----|--------------------|-----|------------------|-----|
| | | | SD | %CV | SD | %CV | SD | %CV |
| High Negative
Panel A | 360 | 0.66 | 0.037 | NA | 0.042 | NA | 0.053 | NA |
| Low Positive
Panel B | 360 | 1.32 | 0.044 | 3.4 | 0.056 | 4.3 | 0.069 | 5.2 |
| Negative Control | 360 | 0.11 | 0.039 | NA | 0.042 | NA | 0.046 | NA |
| Positive Control | 360 | 2.26 | 0.066 | 2.9 | 0.088 | 3.9 | 0.106 | 4.7 |
a Includes repeatability (within-run), between-run, and between-day variability.
b Includes repeatability (within-run), between-run, between-instrument variability.
C. Percent Agreement
A prospective multi-center study was conducted to evaluate the ability of the HAVAb IgG II assay to detect IgG anti-HAV in specimens from individuals at increased risk of HAV infection, individuals with signs and symptoms of hepatitis infection, and of the pediatric population. HAVAb IgG II results on the Alinity i system were compared to the results from the ARCHITECT HAVAB-G assay.
Individuals at Increased Risk of HAV Infection
The percent agreement for specimens from individuals at increased risk of HAV infection (n=250) is summarized in the following table.
- Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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| Individuals at Increased Risk of HAV Infection | ||
|---|---|---|
| ARCHITECT HAVAB-G | ||
| HAVAb IgG II (on Alinity i) | Reactive | Nonreactive |
| Reactive | 119 | 2 |
| Nonreactive | 4 | 125 |
PPA = 96.75% (119/123), 95% CI (91.94%, 98.73%)
NPA = 98.43% (125/127), 95% CI (94.44%, 99.57%)
Individuals with Signs and Symptoms of Hepatitis Infection
The percent agreement for specimens from individuals with signs and symptoms of hepatitis infection (n=499) is summarized in the following table.
| Individuals with Signs and Symptoms of Hepatitis Infection | |||
|---|---|---|---|
| ARCHITECT HAVAB-G | |||
| HAVAb IgG II (on Alinity i) | Reactive | Nonreactive | |
| Reactive | 290 | 2 | |
| Nonreactive | 14 | 193 |
PPA = 95.39% (290/304), 95% CI (92.42%, 97.24%)
NPA = 98.97% (193/195), 95% CI (96.34%, 99.72%)
Pediatric Population
The percent agreement for specimens from the pediatric population (n=105) is summarized in the following table.
| Pediatric Population | ||
|---|---|---|
| ARCHITECT HAVAB-G | ||
| HAVAb IgG II (on Alinity i) | Reactive | Nonreactive |
| Reactive | 90 | 1 |
| Nonreactive | 0 | 14 |
PPA = 100.00% (90/90), 95% CI (95.91%, 100.00%)
NPA = 93.33% (14/15), 95% CI (70.18%, 98.81%)
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X. Conclusion Drawn from Nonclinical Laboratory Studies and Clinical Performance
The results presented in this 510(k) premarket notification demonstrate that the performance of the subject device, HAVAb IgG II, is substantially equivalent to the predicate device, ARCHITECT HAVAB-G (K113704).