Who is the manufacturer of HAVAb IgG II?

Abbott Laboratories filed the 510(k) submission for HAVAb IgG II (K222850).

What is the FDA product code for HAVAb IgG II?

LOL. It is classified under 21 CFR 866.3310 as a Class 2 device in the Microbiology panel.

What is the regulatory pathway for HAVAb IgG II?

510(k) clearance (submission type: Traditional).

What are the predicate devices for HAVAb IgG II?

ARCHITECT HAVAB-G assay (K113704).

Who can help prepare an FDA 510(k) submission like HAVAb IgG II?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

HAVAb IgG II

K222850 · Abbott Laboratories · LOL · Aug 10, 2023 · Microbiology

Device Facts

Record ID	K222850
Device Name	HAVAb IgG II
Applicant	Abbott Laboratories
Product Code	LOL · Microbiology
Decision Date	Aug 10, 2023
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.3310
Device Class	Class 2
Attributes	Pediatric

Intended 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.

Device Story

Automated two-step chemiluminescent microparticle immunoassay (CMIA) for qualitative detection of IgG anti-HAV; performed on Alinity i system. Input: human serum or plasma samples. Process: sample, HAV-coated paramagnetic microparticles, and diluent incubated; IgG anti-HAV binds to microparticles; wash; anti-human IgG acridinium-labeled conjugate added; wash; trigger solutions added; chemiluminescent reaction measured as relative light units (RLU). Output: S/CO value compared to cutoff (≥1.00 reactive, <1.00 nonreactive). Used in clinical laboratories by trained personnel. Results assist clinicians in determining patient immune status to HAV. Benefits: aids in identifying individuals with prior exposure or vaccination.

Clinical Evidence

Prospective multicenter study (n=944) compared HAVAb IgG II on Alinity i to ARCHITECT HAVAB-G. Cohorts: increased risk (n=250), signs/symptoms of hepatitis (n=499), pediatric (n=105). Positive percent agreement: 96.75% (risk), 95.39% (symptoms), 100% (pediatric). Negative percent agreement: 98.43% (risk), 98.97% (symptoms), 93.33% (pediatric). Analytical performance included precision (within-lab and multi-site), interference testing, and analytical sensitivity (15.7 mIU/mL at cutoff).

Technological Characteristics

CMIA technology; automated. Reagents: HAV (human) coated paramagnetic microparticles (0.08% solids), anti-human IgG (mouse monoclonal) acridinium-labeled conjugate, assay diluent. Energy: chemiluminescent reaction. Connectivity: Alinity i system. Calibration: 1-point, traceable to WHO 2nd International Standard (NIBSC 97/646). Controls: negative and positive human plasma-based. Software: Alinity i system operating software.

Indications for Use

Indicated for qualitative detection of IgG anti-HAV in human adult and pediatric (4-21 years) serum and plasma. Used to determine immune status to HAV in patients with signs/symptoms or at risk for hepatitis A. Contraindicated for screening blood, plasma, or tissue donors and for diagnosis of acute HAV infection.

Regulatory Classification

Identification

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

Special Controls

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

Predicate Devices

ARCHITECT HAVAB-G assay (K113704)

Related Devices

K113704 — ARCHITECT HAVAB-G · Abbott Laboratories · Jun 28, 2012
K142758 — ADVIA Centaur HAV total assay · Siemens Healthcare Diagnostics, Inc. · Dec 5, 2014

Submission Summary (Full Text)

{0}------------------------------------------------ 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. Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the agency's name on the right. The symbol features a stylized representation of a caduceus, a symbol associated with medicine and healthcare. To the right of the symbol, the text reads "FDA U.S. FOOD & DRUG ADMINISTRATION" in a clear, sans-serif font. The word "ADMINISTRATION" is placed below "U.S. FOOD & DRUG". 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 {2}------------------------------------------------ # 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) #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW!* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ #### 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 {4}------------------------------------------------ ## 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 | {5}------------------------------------------------ | | 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. {6}------------------------------------------------ | 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. {7}------------------------------------------------ #### 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. {8}------------------------------------------------ | 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: < 1.00 S/CO Reactive: ≥ 1.00 S/CO | Nonreactive: < 1.00 S/CO Reactive: ≥ 1.00 S/CO | | Calibrator(s) | 1 Calibrator | 1 Calibrator | | Control(s) | 2 (Negative and Positive) | 2 (Negative and Positive) | | Within-Laboratory Precision | • 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) 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. | Microparticles – HAV (human) coated microparticles in TRIS buffer. Minimum concentration: 0.08% solids. Preservatives: ProClin 300 and antimicrobial agents. Conjugate – Anti-human IgG (mouse monoclonal) acridinium-labeled conjugate in MES buffer with protein (bovine) stabilizer. Minimum concentration: 0.01 µg/mL. Preservatives: sodium azide and antimicrobial agents. Assay Diluent – Protein (goat) stabilizer in TRIS buffer. Preservatives: ProClin 300 and antimicrobial agents. | ## Comparison of Subject Device (HAVAb IgG II) to Predicate Device (ARCHITECT HAVAB-G) {9}------------------------------------------------ {10}------------------------------------------------ ## 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. {11}------------------------------------------------ ## 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. &quot; Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018. {12}------------------------------------------------ | 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 | {13}------------------------------------------------ #### 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. {14}------------------------------------------------ ## 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. {15}------------------------------------------------ | 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%) {16}------------------------------------------------ # 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).