(323 days)
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.
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 kit includes reagents (Microparticles, Conjugate, Assay Diluent), Calibrator, and Controls. The assay is an automated, two-step immunoassay.
Considering the provided document, the device described is an in vitro diagnostic (IVD) assay (HAVAb IgG II) for the qualitative detection of IgG antibody to hepatitis A virus (IgG anti-HAV). The FDA 510(k) summary focuses on establishing substantial equivalence to a predicate device, not on meeting specific acceptance criteria in the context of an AI/ML medical device's performance evaluation against clinical ground truth.
Therefore, many of the requested criteria (like ground truth establishment by experts, adjudication methods, multi-reader multi-case studies, and separate training/test sets with their ground truth establishment) are generally not applicable to the performance claims made for this in vitro diagnostic device in this FDA submission. The document describes analytical and clinical performance studies typical for an IVD, focusing on agreement with a predicate device and reproducibility/precision, rather than predictive performance of an AI model against a complex clinical endpoint established by human experts.
Based on the provided text, here's a breakdown of the information that is applicable and a clear indication where the requested information is not present or relevant to this type of device submission:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly state "acceptance criteria" in a table format that would typically be found for an AI/ML model for diagnostic imaging (e.g., target sensitivity/specificity values). Instead, it presents performance data for comparison to a predicate device and for reproducibility. The implicit "acceptance criterion" for a 510(k) is demonstrating "substantial equivalence" to a legally marketed predicate device.
However, we can infer some performance metrics presented as evidence of equivalence:
| Performance Metric | Reported Device Performance (HAVAb IgG II) | Predicate Device Performance (ARCHITECT HAVAB-G) (for comparison, not acceptance criteria) |
|---|---|---|
| PPA (Positive Percent Agreement) with Predicate: | ||
| - Increased Risk of HAV Infection Population (n=250) | 96.75% (95% CI: 91.94%, 98.73%) | N/A (this is agreement with the predicate) |
| - Signs and Symptoms of Hepatitis Infection (n=499) | 95.39% (95% CI: 92.42%, 97.24%) | N/A |
| - Pediatric Population (n=105) | 100.00% (95% CI: 95.91%, 100.00%) | N/A |
| NPA (Negative Percent Agreement) with Predicate: | ||
| - Increased Risk of HAV Infection Population (n=250) | 98.43% (95% CI: 94.44%, 99.57%) | N/A |
| - Signs and Symptoms of Hepatitis Infection (n=499) | 98.97% (95% CI: 96.34%, 99.72%) | N/A |
| - Pediatric Population (n=105) | 93.33% (95% CI: 70.18%, 98.81%) | N/A |
| Within-Laboratory Precision (20-Day) | ||
| - High Negative Panel 1 (0.71 S/CO) | SD: 0.028 (Range 0.026-0.045) | N/A (Predicate's Within-Lab Precision: 0.029-0.050 SD for < 1.00 S/CO) |
| - Low Positive Panel 2 (1.25 S/CO) | %CV: 3.2 (Range 2.9-5.8) | N/A (Predicate's Within-Lab Precision: 3.2-4.1 %CV for >= 1.00 S/CO) |
| - Negative Control (0.09 S/CO) | SD: 0.015 (Range 0.011-0.035) | N/A |
| - Positive Control (2.19 S/CO) | %CV: 2.9 (Range 2.5-4.0) | N/A |
| System Reproducibility (Multi-site) | ||
| - High Negative Panel A (0.66 S/CO) | SD: 0.053 | N/A (Predicate's Reproducibility: 0.023-0.116 SD) |
| - Low Positive Panel B (1.32 S/CO) | %CV: 5.2 | N/A (Predicate's Reproducibility: 4.6-10.8 %CV) |
| - Negative Control (0.11 S/CO) | SD: 0.046 | N/A |
| - Positive Control (2.26 S/CO) | %CV: 4.7 | N/A |
2. Sample sizes used for the test set and the data provenance
-
Clinical Performance Test Set (Agreement with Predicate):
- Individuals at Increased Risk of HAV Infection: n=250
- Individuals with Signs and Symptoms of Hepatitis Infection: n=499
- Pediatric Population: n=105
- Total for Agreement Study: 250 + 499 + 105 = 854 specimens.
- Data Provenance: Prospective multi-center study.
- Increased Risk of HAV: collected in California, Colorado, Florida, Illinois, Massachusetts, North Carolina, and Texas.
- Signs and Symptoms of Hepatitis: collected in California, Colorado, Florida, Illinois, Massachusetts, and Texas.
- Pediatric Population: collected in the US (California and Massachusetts) and Belgium.
-
Precision/Reproducibility Test Sets:
- Within-Laboratory Precision: n=80 per sample/control for a representative combination (tested over 20 days, 2 replicates/day). Total tested for this study was 4 reagent/calibrator/instrument combinations.
- System Reproducibility: n=360 per sample/control (tested at 3 sites, with 4 replicates/run, 2 runs/day, 5 days).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not applicable / Not stated. For this IVD device, the "ground truth" for the clinical performance study was the result produced by the legally marketed predicate device (ARCHITECT HAVAB-G). This is a common practice for 510(k) submissions for IVDs. There were no human experts adjudicating results for the purpose of establishing a "ground truth" beyond what the predicate device determined.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Not applicable. As the ground truth was the predicate device's result, no human adjudication method (like 2+1, 3+1) was used or described.
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 assay, not an imaging AI device intended to assist human readers. Therefore, an MRMC study and evaluation of human reader improvement with AI assistance were not performed.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, in spirit. The device (HAVAb IgG II assay) functions as a standalone test; it's an automated immunoassay that generates a qualitative result (Reactive or Nonreactive) without human interpretation in the loop influencing the output beyond sample collection and instrument operation. Its performance was assessed directly against the predicate device's results.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- The "ground truth" for the clinical performance comparison was the results from a legally marketed predicate device (ARCHITECT HAVAB-G assay). In essence, the performance of the new device was compared to the established performance of the predicate. This is a common form of "truth" in demonstrating substantial equivalence for IVDs.
8. The sample size for the training set
- Not explicitly stated in terms of a "training set" for model development. This is an immunoassay, not an AI/ML model where a distinct training dataset size is typically reported. The document describes analytical verification and clinical performance studies, not model training.
9. How the ground truth for the training set was established
- Not applicable. As this is not an AI/ML device in the sense of a machine learning model requiring a training set with a ground truth established by experts for supervised learning, this information is not provided. The development process for an immunoassay does not involve "training data" in the same way an AI/ML model does.
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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
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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 chloridebuffer. Minimum concentration: 0.08% solids. Preservative:ProClin 300. | |
|---|---|
| Conjugate: | Anti-human IgG (mouse, monoclonal) acridinium-labeled conjugatein MES / sodium chloride buffer with protein (bovine) stabilizer andsurfactants. 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 300and 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-HAVConcentration(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-HAVRange(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 andIndications for Use | The HAVAb IgG II assay is achemiluminescent microparticleimmunoassay (CMIA) used for thequalitative detection of IgG antibody tohepatitis A virus (IgG anti-HAV) inhuman adult and pediatric (4 through21 years) serum (collected in serumand serum separator tubes) and plasma(collected in sodium heparin, lithiumheparin, lithium heparin separator,dipotassium EDTA, and tripotassiumEDTA tubes) from patients with signsand symptoms or at risk for hepatitis Aon the Alinity i system.The HAVAb IgG II assay is used todetermine the immune status ofindividuals to hepatitis A virus (HAV)infection.Warning: This assay has not beencleared for use in screening blood,plasma, or tissue donors. This assaycannot be used for the diagnosis ofacute HAV infection.Assay performance characteristics havenot been established when the HAVAbIgG II assay is used in conjunctionwith other hepatitis assays. | The ARCHITECT HAVAB-G assay is achemiluminescent microparticleimmunoassay (CMIA) for the qualitativedetection of IgG antibody to hepatitis Avirus (IgG anti-HAV) in human adult andpediatric serum from patients with signsand symptoms or at risk for hepatitis. TheARCHITECT HAVAB-G assay is used todetermine the immune status of individualsto hepatitis A virus infection.Warning: This assay has not been FDAcleared or approved for the screening ofblood or plasma donors. This assaycannot be used for the diagnosis of acuteHAV infection.Assay performance characteristics havenot been established when theARCHITECT HAVAB-G assay is used inconjunction with other hepatitis assays. |
| Methodology | Chemiluminescent MicroparticleImmunoassay | Chemiluminescent MicroparticleImmunoassay |
| Antigen Used | HAV (Strain pHM175) | HAV (Strain pHM175) |
| Interpretation ofResults | Nonreactive: < 1.00 S/COReactive: ≥ 1.00 S/CO | Nonreactive: < 1.00 S/COReactive: ≥ 1.00 S/CO |
| Calibrator(s) | 1 Calibrator | 1 Calibrator |
| Control(s) | 2 (Negative and Positive) | 2 (Negative and Positive) |
| Within-LaboratoryPrecision | • 0.011 – 0.045 SD(for samples < 1.00 S/CO)• 2.5 – 5.8 %CV(for samples ≥ 1.00 S/CO) | • 0.029 – 0.050 SD(for samples < 1.00 S/CO)• 3.2–4.1 %CV(for samples ≥ 1.00 S/CO) |
| Similarities and Differences Between Subject & Predicate Device | ||
| Subject Device:HAVAb IgG II | Predicate Device:ARCHITECT HAVAB-G (K113704) | |
| Reproducibility | • 0.046–0.053 SD(for samples < 1.00 S/CO)• 4.7–5.2 %CV(for samples ≥ 1.00 S/CO) | • 0.023–0.116 SD(for samples < 1.00 S/CO)• 4.6–10.8 %CV(for samples ≥ 1.00 S/CO) |
| General Device Characteristic Differences | ||
| Type of Specimen | Serum and Plasma | Serum |
| Platform | Alinity i system | ARCHITECT i System |
| Components | Microparticles – HAV (human) coatedmicroparticles in MOPS / potassiumchloride buffer. Minimumconcentration: 0.08% solids.Preservative: ProClin 300.Conjugate – Anti-human IgG (mouse,monoclonal) acridinium-labeledconjugate in MES / sodium chloridebuffer with protein (bovine) stabilizerand surfactants. Minimumconcentration: 0.01 µg/mL.Preservatives: ProClin 300 andProClin 950.Assay Diluent – Assay diluentcontaining protein (goat, mouse, andbovine) stabilizers in TRIS buffer andsurfactant. Preservatives: ProClin 300and ProClin 950. | Microparticles – HAV (human) coatedmicroparticles in TRIS buffer. Minimumconcentration: 0.08% solids. Preservatives:ProClin 300 and antimicrobial agents.Conjugate – Anti-human IgG (mousemonoclonal) acridinium-labeled conjugatein MES buffer with protein (bovine)stabilizer. Minimum concentration:0.01 µg/mL. Preservatives: sodium azideand antimicrobial agents.Assay Diluent – Protein (goat) stabilizer inTRIS buffer. Preservatives: ProClin 300and antimicrobial agents. |
Comparison of Subject Device (HAVAb IgG II) to Predicate Device (ARCHITECT HAVAB-G)
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VIII. Summary of Nonclinical Performance
A. Within-Laboratorv Precision (20-Dav)
A study was performed based on guidance from CLSI EP05-A3. Testing was conducted using 2 lots of the HAVAb IgG II reagents, 2 lots of the HAVAb IgG II Calibrator, 1 lot of the HAVAb IgG II Controls, and 2 instruments. Two controls and 2 human serum panels were tested in a minimum of 2 replicates twice per day on 20 days on 4 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot are paired with 1 instrument. The performance from a representative combination is shown in the following table.
| Within-Run(Repeatability) | Within-Laboratorya | |||||
|---|---|---|---|---|---|---|
| Sample | n | Mean(S/CO) | SD | %CV | SD(Rangeb) | %CV(Rangeb) |
| High Negative Panel 1 | 80 | 0.71 | 0.025 | NA | 0.028(0.026-0.045) | NA |
| Low Positive Panel 2 | 80 | 1.25 | 0.040 | 3.2 | 0.040(0.036-0.078) | 3.2(2.9-5.8) |
| Negative Control | 80 | 0.09 | 0.011 | NA | 0.015(0.011-0.035) | NA |
| Positive Control | 80 | 2.19 | 0.053 | 2.4 | 0.063(0.055-0.090) | 2.9(2.5-4.0) |
NA = Not applicable
a Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV across 4 reagent lot/calibrator lot/instrument combinations.
* 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 | IncreasedRisk ofHAVInfection | Signs andSymptomsofHepatitisInfection | PediatricPopulation | ||||
|---|---|---|---|---|---|---|---|
| Adults | Pediatrics | ||||||
| HighPrevalenceArea(s)for HAV | LowPrevalenceArea(s)for HAV | HighPrevalenceArea(s)for HAV | LowPrevalenceArea(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 NegativePanel A | 360 | 0.66 | 0.037 | NA | 0.042 | NA | 0.053 | NA |
| Low PositivePanel 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).
§ 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.