Anti-HCV Next
Device Facts
| Record ID | K252424 |
|---|---|
| Device Name | Anti-HCV Next |
| Applicant | Abbott Laboratories |
| Product Code | MZO · Microbiology |
| Decision Date | Apr 28, 2026 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3169 |
| Device Class | Class 2 |
Indications for Use
The Anti-HCV Next assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of antibodies to hepatitis C virus (anti-HCV) in human adult serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin, lithium heparin separator, sodium citrate, disodium EDTA, tripotassium EDTA, dipotassium EDTA, and dipotassium EDTA separator tubes) on the Alinity i system. The Anti-HCV Next assay results, in conjunction with other laboratory results and clinical information, may be used to aid in the presumptive diagnosis of hepatitis C virus (HCV) infection in persons with signs and symptoms of hepatitis, persons at risk for HCV infection, and pregnant women. The test does not determine the state of infection or associated disease. Not cleared for use in screening blood, plasma, or tissue donors.
Device Story
Automated CMIA assay for qualitative detection of anti-HCV antibodies; utilizes Alinity i system. Input: human serum or plasma. Process: sample, streptavidin-coated paramagnetic microparticles (precomplexed with biotinylated HCV constructs), and acridinium-labeled HCV conjugates incubated to form sandwich; wash cycles; addition of Pre-Trigger and Trigger solutions. Output: chemiluminescent RLU signal proportional to anti-HCV concentration; compared to cutoff RLU from active calibration. Used in clinical laboratories; operated by trained personnel. Results aid clinicians in presumptive HCV diagnosis; does not determine infection state or disease status.
Clinical Evidence
Clinical study of 3,732 specimens (symptomatic, at-risk, pregnant). Overall PPA 99.50% (98.20-99.86% CI); overall NPA 97.24% (96.63-97.74% CI). Performance validated against consensus of comparator and two additional FDA-cleared assays, with HCV RNA testing for indeterminate results. Bench testing included precision (20-day, 6.1% CV for positive control), seroconversion sensitivity, analytical specificity, and high-dose hook effect.
Technological Characteristics
CMIA technology. Reagents: streptavidin-coated paramagnetic microparticles, biotinylated HCV antigens/peptides, acridinium-labeled conjugates. Buffer: pyrophosphate-buffered saline. Automated on Alinity i system. Calibration: 30-day validity via RFID/2D barcode. Sterilization: N/A (reagent kit). Connectivity: Alinity i system integration.
Indications for Use
Indicated for qualitative detection of anti-HCV antibodies in human adult serum and plasma. Used as an aid in presumptive diagnosis of HCV infection in symptomatic individuals, those at risk for HCV, and pregnant women. Not for screening blood, plasma, or tissue donors.
Regulatory Classification
Identification
A hepatitis C virus (HCV) antibody test is identified as an in vitro diagnostic device intended for use with human serum, plasma, or other matrices as a prescription device that aids in the diagnosis of HCV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis C infection. The test is not intended for screening blood, plasma, cell, or tissue donors.
Special Controls
*Classification.* Class II (special controls). The special controls for this device are:(1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the test is not intended for the screening of blood, plasma, and cell or tissue donors. (ii) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: (A) When appropriate, the performance characteristics of the test have not been established in populations of immunocompromised or immunosuppressed patients or, other special populations where test performance may be affected. (B) The detection of HCV antibodies indicates a present or past infection with hepatitis C virus, but does not differentiate between acute, chronic, or resolved infection. (C) The specimen types for which the device has been cleared, and that use of the test with specimen types other than those specifically cleared for this device may result in inaccurate test results. (D) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results. (E) A non-reactive test result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the test. (iii) A detailed explanation of the principles of operation and procedures for performing the test. (2) Design verification and validation must include the following: (i) A detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, and design of the antigen(s) and capture antibody(ies) sequences, rationale for the selected epitope(s), degree of amino acid sequence conservation of the target, and the design and nature of all primary, secondary, and subsequent standards used for calibration. (ii) Documentation and characterization ( *e.g.,* supplier, determination of identity, and stability) of all critical reagents (including description of the antigen(s) and capture antibody(ies)), and protocols for maintaining product integrity throughout its labeled shelf life.(iii) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (iv) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (v) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vi) All stability protocols, including acceptance criteria. (vii) Final release test results for each lot used in clinical studies. (viii) Multisite reproducibility study that includes the testing of three independent production lots. (ix) Analytical performance studies and results for determining the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility) including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, specimen stability, reagent stability, and cross-genotype antibody detection sensitivity, when appropriate. (x) Analytical sensitivity of the test is the same or better than that of other cleared or approved tests. (xi) Detailed documentation of clinical performance testing from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved HCV antibody test, or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with an acceptable number of HCV positive and negative samples in applicable risk categories. Additional relevant patient groups must be validated as appropriate. The samples may be a combination of fresh and repository samples, sourced from geographically diverse areas. The study designs, including number of samples tested, must be sufficient to meet the following criteria: (A) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 95 percent. (B) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 96 percent. (3) For any HCV antibody test intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Clinical studies must be conducted at PoC sites. (ii) Additional labeling must include a brief summary of the instructions for use that are appropriate for use in a PoC environment.
Predicate Devices
- Liaison XL Murex HCV Ab (P190011)
Submission Summary (Full Text)
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY AND INSTRUMENT
## I Background Information:
A 510(k) Number
K252424
B Applicant
Abbott Laboratories
C Proprietary and Established Names
Anti-HCV Next
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| MZO | Class II | 21 CFR 866.3169 - Hepatitis C Virus (HCV) Antibody Test | MI - Microbiology |
## II Submission/Device Overview:
A Purpose for Submission:
Clearance for marketing of the Anti-HCV Next Reagent Kit, Anti-HCV Next Calibrator, and Anti-HCV Next Controls to be used on the Alinity i analyzer.
B Measurand:
Anti-HCV antibodies
C Type of Test:
Chemiluminescent microparticle immunoassay (CMIA)
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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III Intended Use/Indications for Use:
A Intended Use(s):
The Anti-HCV Next assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of antibodies to hepatitis C virus (anti-HCV) in human adult serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin, lithium heparin separator, sodium citrate, disodium EDTA, tripotassium EDTA, dipotassium EDTA, and dipotassium EDTA separator tubes) on the Alinity i system.
The Anti-HCV Next assay results, in conjunction with other laboratory results and clinical information, may be used to aid in the presumptive diagnosis of HCV infection in persons with signs and symptoms of hepatitis, persons at risk for hepatitis C infection, and pregnant women. The test does not determine the state of infection or associated disease. Not cleared for use in screening blood, plasma, or tissue donors.
B Indication(s) for Use:
See Intended Use(s) above.
C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
D Special Instrument Requirements:
For use on the Alinity i system.
IV Device/System Characteristics:
A Device Description:
The Anti-HCV Next assay is an automated, combined one-step/two-step immunoassay for the qualitative detection of anti-HCV in human serum and plasma using chemiluminescent microparticle immunoassay (CMIA) technology.
Sample, streptavidin-coated paramagnetic microparticles precomplexed with biotinylated HCV constructs, acridinium-labeled recombinant and peptide conjugates, and assay diluent are combined and incubated. The anti-HCV present in the sample binds to the HCV coated microparticles and to the acridinium-labeled conjugates, forming a sandwich. The mixture is washed. In a second step, additional acridinium-labeled HCV antigen 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 anti-HCV in the sample and the RLU detected by the system optics.
The presence or absence of anti-HCV 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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This product is composed of 4 components, which are packaged as a 2-cartridge reagent set. Both cartridges are required to perform the assay.
Volumes (mL) listed in the following table indicate the volume per cartridge set.
| List Number (LN) | 06T7921 | 06T7931 |
| --- | --- | --- |
| Tests per cartridge | 100 | 500 |
| Number of cartridges per kit | 2 | 2 |
| Tests per kit | 200 | 1000 |
| Microparticles | 6.6 mL | 27.0 mL |
| Conjugate 1 | 4.2 mL | 13.8 mL |
| Assay Diluent | 5.9 mL | 14.0 mL |
| Conjugate 2 | 6.1 mL | 26.5 mL |
- Microparticles: Streptavidin-coated microparticles precomplexed with biotinylated HCV antigen (E. coli, recombinant) and biotinylated HCV Core synthetic peptide in pyrophosphate-buffered saline with surfactants. Minimum concentration: 0.05% solid Preservative: sodium azide.
- Conjugate: Acridinium-labeled HCV antigen (E. coli, recombinant) and acridinium-labeled HCV Core synthetic peptide conjugate in pyrophosphate-buffered saline. Minimum concentration: 10 ng/mL. Preservative: sodium azide.
- Assay Diluent: Pyrophosphate buffer with protein additives (bovine) and detergent. Preservatives: sodium azide and antimicrobial agents.
- Conjugate 2: Acridinium-labeled HCV antigen (E. coli, recombinant) conjugate in pyrophosphate-buffered saline. Minimum concentration: 0.01 ng/mL. Preservative: sodium azide.
Anti-HCV Next Calibrator and Anti-HCV Next Controls are sold separately.
## Interpretation of Results
### Initial Results
| S/CO | Instrument Interpretation | Retest Procedure |
| --- | --- | --- |
| 0.00 - < 0.90 | Nonreactive | No retest required. |
| 0.90 - < 1.00 | Grayzone | Retest in duplicate. |
| ≥ 1.00 | Reactive | No retest required. |
### Final Interpretation
| Initial Result | Retest Result | Result | Interpretation |
| --- | --- | --- | --- |
| Nonreactive | No retest required. | Nonreactive | Anti-HCV not detected; does not exclude the possibility of exposure to HCV. |
| Grayzone | If 2 results are ≥ 1.00 S/CO | Reactive | Presumptive evidence of anti-HCV; follow |
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| Initial Result | Retest Result | Result | Interpretation |
| --- | --- | --- | --- |
| Reactive | If 2 or 3 results (including initial result) are < 1.00 S/CO | Nonreactive | medical guidelines for recommendations for supplemental testing^{12}
Anti-HCV not detected; does not exclude the possibility of exposure to HCV. |
| | No retest required. | Reactive | Presumptive evidence of anti-HCV; follow medical guidelines for recommendations for supplemental testing^{12}. |
## B Instrument Description Information:
1. **Instrument Name:**
Alinity i system
2. **Specimen Identification:**
Specimens are automatically identified via a built-in barcode reader or can be manually scanned using the System Control Module.
3. **Specimen Sampling and Handling:**
The samples may be loaded on the system in any order. The system pipettor robot dispenses and aspirates liquids, as appropriate for each reaction. Sample handling and reagent transport is performed by a handler robot. This automated system manages up to 150 samples simultaneously using a robotic handler to prevent contamination during continuous loading.
4. **Calibration:**
The system uses RFID or 2D barcodes for calibration, which needs to be performed once every 30 days.
The Anti-HCV Next Calibrator is provided at one level positive for HCV antibody. Calibration data is valid for up to 30 days.
**Calibrator 1:** Contains recalcified, heat inactivated, human plasma reactive for anti-HCV. Preservatives: sodium azide and antimicrobial agents.
The Anti-HCV Next Calibrator is manufactured and referenced to an internal reference standard. The S/CO is $5.56 \pm 12.7\%$.
5. **Quality Control:**
QC testing is recommended every 24 hours or upon reagent lot changes to ensure results stay within target ranges.
**Controls**
- **Negative Control:** Contains recalcified, human plasma. Target 0.02 S/CO (NA-0.5 S/CO)
- **Positive Control:** Contains recalcified, heat-inactivated, human plasma reactive for anti-HCV. Target 3.6 S/CO (1.8-5.4 S/CO)
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- Preservatives: sodium azide and antimicrobial agents.
The Alinity i Anti-HCV Next positive control is referenced to an internal reference standard.
## V Substantial Equivalence Information:
### A Predicate Device Name(s):
LIAISON XL MUREX HCV Ab; LIAISON XL MUREX Control HCV Ab
### B Predicate 510(k) Number(s):
P190011
### C Comparison with Predicate(s):
| Device & Predicate Device(s): | K252424 | P190011 |
| --- | --- | --- |
| Device Trade Name | Anti-HCV Next | LIAISON XL MUREX HCV Ab |
| Regulation Number | 21 CFR 866.3169 | Same |
| Regulation Name | Hepatitis C Virus (HCV) Antibody Test | Same |
| Regulatory Class | Class II | Class III |
| Product Code | MZO | Same |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | The Anti-HCV Next assay is a chemiluminescent microparticle immunoassay (CMIA) used for the qualitative detection of antibodies to hepatitis C virus (anti-HCV) in human adult serum (collected in serum and serum separator tubes) and plasma (collected in sodium heparin, lithium heparin, lithium heparin separator, sodium citrate, disodium EDTA, tripotassium EDTA, dipotassium EDTA, and dipotassium EDTA separator tubes) on the Alinity i system. The Anti-HCV Next assay results, in conjunction with other laboratory results and clinical information, may be used to aid in the presumptive diagnosis of hepatitis C virus (HCV) infection in persons with signs and symptoms of hepatitis, persons at risk for HCV infection, and pregnant women. The test does not determine the state of infection or associated disease. Not cleared for use in screening | The LIAISON XL MUREX HCV Ab assay is an in vitro chemiluminescent immunoassay (CLIA) for the qualitative determination of specific antibodies to hepatitis C virus (anti-HCV) in human adult and pediatric (2-21 years) serum and plasma (lithium and sodium heparin, sodium citrate and di-potassium EDTA) samples including separator tubes, on the LIAISON XL Analyzer. It is intended to be used as an aid in the diagnosis of HCV infection. The assay may also be used as an aid in the diagnosis of HCV infection in pediatric subjects and in pregnant women. The test does not determine the state of infection or associated disease. The assay is not intended for use in screening blood, plasma, or tissue donors. |
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| | blood, plasma, or tissue donors. | |
| --- | --- | --- |
| Analyte Measured | Hepatitis C Virus (HCV) Antibody | Same |
| **General Device Characteristic Differences** | | |
| Test Principle | Chemiluminescent microparticle immunoassay (CMIA). Qualitative, 1-step/2-step | Chemiluminescent immunoassay (CLIA). Qualitative 2-step |
| Capture Antigens | Streptavidin-coated microparticles precomplexed with biotinylated NS3h antigen and Core Peptide | Magnetic particle coated with HCV core and NS4 recombinant antigens, streptavidin-coated magnetic microparticles and aqueous Biotinylated HCV Nonstructural protein 3 (NS3) recombinant antigen. |
| Components | Microparticles – Streptavidin-coated microparticles precomplexed with biotinylated HCV antigen (E coli, recombinant) and biotinylated HCV core synthetic peptide in pyrophosphate-buffered saline with surfactants. Minimum concentration: 0.05% solids. Preservative: sodium azide. Conjugate 1 – Acridinium-labeled HCV antigen (E coli, recombinant) and acridinium-labeled HCV core synthetic peptide conjugate in pyrophosphate-buffered saline. Minimum concentration: 10 ng/mL. Preservative: sodium azide. Conjugate 2 – Acridinium-labeled HCV antigen (E coli, recombinant) conjugate in pyrophosphate-buffered saline. Minimum concentration: 0.01 ng/mL. Preservative: sodium azide. Assay Diluent – Pyrophosphate buffer with protein additives (bovine) and detergent. Preservatives: sodium azide and antimicrobial agents. | Magnetic particles [SORB] - Magnetic particles coated with HCV core and NS4 recombinant antigens (produced in baculovirus and E. coli respectively), streptavidin-coated magnetic particles, BSA, PBS buffer, EDTA, preservatives. HCV NS3 Antigen [Ag] - Biotinylated HCV NS3 recombinant antigen (produced in E.coli), MES buffer, preservatives. Conjugate [CONJ] - Mouse monoclonal IgG to human IgG conjugated to an isoluminol derivative, fetal calf serum, phosphate buffer, 0.2% ProClin 300, preservatives, an inert red dye. Specimen diluent [DIL|SPE] - BSA, casein, non-specific recombinant protein (produced in E.coli), phosphate buffer, EDTA, preservatives, an inert blue dye. |
| Type of Specimen | Serum and Plasma | Serum and Plasma |
| Calibrator(s) | 1 Calibrator | 1Calibrator |
| Calibration Storage | Maximum of 30 days | Maximum of 8 weeks |
| Control(s) | 2 Controls (1 Negative, 1 Positive) Negative Control (negative | Controls (1 Negative, 1 Positive) Negative Control (human |
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| | recalcified human plasma)
Positive Control (recalcified, heat-inactivated, human plasma reactive for anti-HCV) | serum/plasma non-reactive for HCV antigens and antibodies)
Positive Control (inactivated human serum/plasma reactive for HCV antibodies) |
| --- | --- | --- |
| Instrument Platform | Alinity i system | LIAISON XL Analyzer |
VI Standards/Guidance Documents Referenced:
CLSI C24 4th Edition (Replaces C24-A3) Statistical Quality Control for Quantitative Measurement Procedures: Principles and Definitions
CLSI EP05-A3 Third Edition (Reaffirmed: September 2019) Evaluation of Precision of Quantitative Measurement Procedures
CLSI EP07 3rd Edition Interference Testing in Clinical Chemistry
CLSI EP12 3rd Edition Evaluation of Qualitative Binary Output Examination Performance
CLSI EP17-A2 Second Edition Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
CLSI EP25 2nd Edition Evaluation of Stability of In Vitro Medical Laboratory Test Reagents
CLSI EP35 1st Edition Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures
CLSI EP37 1st Edition Supplemental Tables for Interference Testing in Clinical Chemistry
VII Performance Characteristics (if/when applicable):
A Analytical Performance:
1. Precision/Reproducibility: Within-Laboratory Precision (20-Day)
A study was performed based on guidance from CLSI EP05-A3. Testing was conducted using 3 lots of the Anti-HCV Next reagents, 3 lots of the Anti-HCV Next Calibrator, 3 lots of the Anti-HCV Next Controls, and 2 instruments. Two controls and 3 recalcified human plasma panels were tested in 2 replicates twice per day on 20 days on 3 reagent lot/calibrator lot combinations on 2 instruments, where a unique reagent lot and a unique calibrator lot are paired. The performance is shown in the following table.
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| Sample | n | Mean (S/CO) | Repeatability (Within-Run) | | Between-Run | | Between-Day | | Within-Laboratory1 | | Between-Lot | | Between-Instrument | | Overall Within-Laboratory2 | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Negative Control | 480 | 0.01 | 0.001 | N/A | 0.000 | N/A | 0.000 | N/A | 0.001 | N/A | 0.006 | N/A | 0.000 | N/A | 0.006 | N/A |
| Positive Control | 480 | 3.62 | 0.088 | 2.4 | 0.042 | 1.2 | 0.094 | 2.6 | 0.136 | 3.8 | 0.143 | 3.9 | 0.096 | 2.7 | 0.219 | 6.1 |
| Panel 1 | 480 | 0.79 | 0.019 | N/A | 0.010 | N/A | 0.021 | N/A | 0.030 | N/A | 0.035 | N/A | 0.026 | N/A | 0.052 | N/A |
| Panel 2 | 480 | 1.22 | 0.025 | 2.1 | 0.020 | 1.6 | 0.037 | 3.0 | 0.049 | 4.0 | 0.052 | 4.3 | 0.038 | 3.1 | 0.081 | 6.6 |
| Panel 3 | 480 | 3.12 | 0.065 | 2.1 | 0.056 | 1.8 | 0.083 | 2.7 | 0.119 | 3.8 | 0.148 | 4.7 | 0.088 | 2.8 | 0.209 | 6.7 |
<a>1</a> Includes repeatability (within-run), between-run, and between-day variability.
<a>2</a> Anti-HCV Next reagent lot and Anti-HCV Next calibrator lot are confounded, and the confounding effect is represented by between-lot.
<a>3</a> Includes repeatability (within-run), between-run, between-day, between-lot, and between-instrument variability.
## System Reproducibility
A study was performed based on guidance from CLSI EP05-A3. Testing was conducted at each of 3 testing sites using 1 lot of the Anti-HCV Next reagents, 1 lot of the Anti-HCV Next Calibrator, 1 lot of the Anti-HCV Next Controls, and 1 instrument. Two controls and 3 recalcified human plasma panels were tested in 4 replicates at 2 separate times per day on 5 different days. The performance is shown in the following table.
| Sample | n | Mean (S/CO) | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility3 | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Negative Control | 120 | 0.02 | 0.000 | N/A | 0.000 | N/A | 0.000 | N/A | 0.000 | N/A | 0.000 | N/A |
| Positive Control | 120 | 3.47 | 0.049 | 1.4 | 0.034 | 1.0 | 0.000 | 0.0 | 0.000 | 0.0 | 0.059 | 1.7 |
| Panel 1 | 120 | 0.77 | 0.041 | N/A | 0.000 | N/A | 0.000 | N/A | 0.009 | N/A | 0.042 | N/A |
| Panel 2 | 120 | 1.19 | 0.066 | 5.5 | 0.000 | 0.0 | 0.000 | 0.0 | 0.020 | 1.6 | 0.068 | 5.7 |
| Panel 3 | 120 | 3.02 | 0.106 | 3.5 | 0.000 | 0.0 | 0.000 | 0.0 | 0.046 | 1.5 | 0.115 | 3.8 |
<a>1</a> Includes repeatability (within-run), between-run, between-day, and between-site variability.
2. Linearity:
N/A
3. Analytical Specificity/Interference:
a) Potentially Interfering Endogenous Substances and Potentially Interfering Drugs
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Studies were performed based on guidance from CLSI EP07, 3rd ed. Each substance was evaluated at 2 levels of the analyte (approximately 0.80 S/CO and 1.20 S/CO).
The studies demonstrated that the Anti-HCV Next assay is not susceptible to interference at the following interferent levels.
| Potentially Interfering Endogenous Substance | Interferent Level |
| --- | --- |
| Bilirubin (conjugated) | 40 mg/dL |
| Bilirubin (unconjugated) | 40 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Total Protein | 15 g/dL |
| Triglycerides | 1500 mg/dL |
| Potentially Interfering Drug | Interferent Level |
| --- | --- |
| Acetaminophen | 15.6 mg/dL |
| Acetylsalicylic Acid | 3.0 mg/dL |
| Amoxicillin | 5.4 mg/dL |
| Ascorbic Acid | 5.25 mg/dL |
| Biotin | 4250 ng/mL |
| Glecaprevir + Pibrentasvir | 1791 ng/mL + 330 ng/mL |
| Ibuprofen | 21.9 mg/dL |
| Pegylated (PEG) Interferon-alpha2a | 0.18 mg/L |
| Ribavirin | 1200 mg/L |
## b) Cross-reactivity (other specimen conditions or disease states)
The Anti-HCV Next assay was evaluated for potential interference using specimens from individuals with other disease states or medical conditions unrelated to HCV infection. The results were compared to a commercially available anti-HCV assay and data are summarized in the following table.
| Category | n | Commercially Available Assay | | | |
| --- | --- | --- | --- | --- | --- |
| | | Reactive | | Nonreactive | |
| | | Anti-HCV Next | | Anti-HCV Next | |
| | | Reactive | Nonreactive | Reactive | Nonreactive |
| Alcoholic Liver Disease | 17 | 0 | 0 | 0 | 17 |
| Anti-Dengue Virus | 12 | 0 | 0 | 1 | 11 |
| Anti-Double-Stranded DNA (Anti-dsDNA) | 20 | 9 | 0 | 1 | 10 |
| Anti-Hepatitis E Virus (Anti-HEV) | 12 | 0 | 0 | 0 | 12 |
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| Category | n | Commercially Available Assay | | | |
| --- | --- | --- | --- | --- | --- |
| | | Reactive | | Nonreactive | |
| | | Anti-HCV Next | | Anti-HCV Next | |
| | | Reactive | Nonreactive | Reactive | Nonreactive |
| Anti-Herpes Simplex Virus (Anti-HSV) Type 1/2 | 12 | 0 | 0 | 0 | 12 |
| Anti-Mitochondrial Antibodies (AMA) | 2 | 0 | 0 | 0 | 2 |
| Anti-Neutrophil Cytoplasmic Antibodies (ANCA) | 12 | 0 | 0 | 0 | 12 |
| Anti-Nuclear Antibodies (ANA) | 12 | 0 | 0 | 0 | 12 |
| Anti-Parvovirus B19 | 12 | 0 | 0 | 0 | 12 |
| Anti-Rubella Virus | 11 | 0 | 0 | 0 | 11 |
| Anti-Varicella Zoster Virus | 12 | 1 | 0 | 0 | 11 |
| Autoimmune Hepatitis | 20 | 1 | 0 | 0 | 19 |
| Cytomegalovirus (CMV) (Acute or Chronic) | 12 | 1 | 0 | 0 | 11 |
| E Coli | 10 | 0 | 0 | 0 | 10 |
| Elevated Total Bilirubin | 12 | 5 | 0 | 0 | 7 |
| Elevated Total Protein | 12 | 4 | 0 | 0 | 8 |
| Epstein-Barr Virus (EBV) (Acute or Chronic) | 12 | 0 | 0 | 0 | 12 |
| Fatty Liver Disease | 16 | 0 | 0 | 0 | 16 |
| Hemodialysis Patients | 12 | 1 | 0 | 0 | 11 |
| Hepatitis A (Acute or Chronic) | 12 | 0 | 0 | 0 | 12 |
| Hepatitis A Virus (HAV) Vaccination | 12 | 1 | 0 | 0 | 11 |
| Hepatitis B (Acute or Chronic) | 33 | 0 | 0 | 0 | 33 |
| Hepatitis B Virus (HBV) | 12 | 0 | 0 | 0 | 12 |
| HBV Vaccination | 22 | 10 | 0 | 1 | 11 |
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| Category | n | Commercially Available Assay | | | |
| --- | --- | --- | --- | --- | --- |
| | | Reactive | | Nonreactive | |
| | | Anti-HCV Next | | Anti-HCV Next | |
| | | Reactive | Nonreactive | Reactive | Nonreactive |
| Hepatitis D (Acute or Chronic) | 11 | 0 | 0 | 1 | 10 |
| Human Anti-Mouse Antibodies (HAMA) | 12 | 0 | 0 | 0 | 12 |
| Human Immunodeficiency Virus (HIV) | 12 | 0 | 0 | 0 | 12 |
| Human T-Cell Lymphotropic Virus (HTLV) | 12 | 0 | 0 | 0 | 12 |
| Hyper IgG or IgM (Monoclonal) | 10 | 0 | 0 | 0 | 10 |
| Influenza Vaccine Recipients | 12 | 1 | 0 | 0 | 11 |
| Non-Alcoholic Steatohepatitis (NASH) | 33 | 1 | 0 | 0 | 32 |
| Non-Specific Heterophile Antibodies | 11 | 0 | 0 | 0 | 11 |
| Pregnant and Multiparous Females | 24 | 0 | 0 | 0 | 24 |
| Primary Biliary Cirrhosis | 33 | 2 | 0 | 0 | 31 |
| Rheumatoid Factor (RF) | 22 | 4 | 0 | 0 | 18 |
| SARS-CoV-2 Vaccinees (Recent) | 12 | 0 | 0 | 0 | 12 |
| Smooth Muscle Antibodies (SMA) | 12 | 0 | 0 | 0 | 12 |
| Systemic Lupus Erythematosus (SLE) | 12 | 0 | 0 | 0 | 12 |
| Toxic Hepatitis (Acute or Chronic) | 22 | 7 | 0 | 1 | 14 |
| Toxoplasmosis IgG Positive | 12 | 2 | 0 | 0 | 10 |
| Treponema Pallidum | 12 | 0 | 0 | 0 | 12 |
| Yeast Infection | 10 | 3 | 0 | 0 | 7 |
| Total | 615 | 53 | 0 | 5 | 557 |
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c) Hook Effect
A study was performed to assess the high dose hook effect. A high-level anti-HCV positive sample, reactive at 1:78,125 dilution, was still reactive when tested undiluted with the Anti-HCV Next assay. The undiluted high-level anti-HCV positive sample mean result was 39.98 S/CO. The Anti-HCV Next assay is not susceptible to false negative results due to a high-dose-hook effect.
4. Assay Reportable Range: N/A
5. Stability, Expected Values (Controls, Calibrators, or Methods, and samples):
a) Reagent stability
Reagent Shelf-Life Stability:
The purpose of this study was to establish the expiration dating of the Anti-HCV Next Reagent Kit when stored at the recommended storage temperature (2 to 8°C).
Four reagent lots were evaluated (3 lots of the 100 kit size and 1 lot of the 500 kit size) at time 0 (baseline) and once a month after storage at 2 to 8°C over a 13-month period.
Regression analysis was performed to calculate the % shift of the S/CO value from each time point to the intercept (regressed baseline).
The data supports a reagent shelf-life stability claim of up to 12 months when stored unopened at the recommended storage condition (2 to 8°C).
Calibrator and controls shelf-life stability:
The purpose of this study was to establish the expiration dating of the Anti-HCV Next calibrator and controls when stored at the recommended storage temperature (2 to 8°C).
The data supports a shelf-life stability claim of up to 18 months for the calibrators and controls when stored unopened at the recommended storage condition (2 to 8°C).
Reagent Storage Stability-In Use
The purpose of this study was to determine the time period over which the Alinity i reagents can be kept in the refrigerator and alternately moved back and forth from the refrigerator to the analyzer, simulating customer use over time.
The data supports a reagent in-use stability claim of up to 12 months when stored at the recommended storage condition (2 to 8°C).
Reagent Storage Stability-Inverted Reagent Storage (INV)
The purpose of this study was to demonstrate stability of the Anti-HCV Next Reagents when the reagent kit is stored in an inverted position. The data supports a reagent inverted stability claim of up to 12 months when stored at the recommended storage condition (2 to 8°C).
b) Specimen Stability
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The use of the Anti-HCV Next assay is supported for testing serum and plasma specimens that have been stored at the following conditions:
- -20°C or colder off the cells/clot/gel up to 3 months
- 2 to 8°C on and off the cells/clot/gel up to 7 days
- 15 to 30°C on and off the cells/clot/gel up to 3 days
- 6 Freeze/Thaw Cycles after storage at 2 to 8°C at -20°C or colder
## 6. Analytical Sensitivity:
### Seroconversion Sensitivity
To determine the seroconversion sensitivity, 31 seroconversion panels obtained from commercial vendors were tested on the Alinity i system using the Anti-HCV Next assay. The panel results were compared to a commercially available anti-HCV assay. The Anti-HCV Next assay detected 6 panels as reactive ahead, 1 panel as reactive behind, and 24 panels equal to the commercially available anti-HCV assay. Ahead and behind were determined based on the first reactive result, followed by continuously reactive results (in subsequent donations bleeds, if applicable). Data are summarized in the following table.
| Panel ID | Days to First Continuously Reactive Result | | Difference in Days a |
| --- | --- | --- | --- |
| | Anti-HCV Next | Commercially Available Anti-HCV Assay | |
| 6215 | 20 | 20 | 0 |
| 6221 | 0 | 0 | 0 |
| 6222 | 36 | 36 | 0 |
| 6224 | 7 | 7 | 0 |
| 6225 | 45 | 73 | -28 |
| 6226 | 30 | 30 | 0 |
| 6227 | 74 | 74 | 0 |
| 6228 | 21 | 28 | -7 |
| 6229 | 17 | 10 | 7 |
| 9041 | 62 | 62 | 0 |
| 9044 | 21 | 21 | 0 |
| 9045 | 32 | 32 | 0 |
| 9046 | 69 | 69 | 0 |
| 9047 | 28 | 28 | 0 |
| 9054 | 82 | 82 | 0 |
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| Panel ID | Days to First Continuously Reactive Result | | Difference in Daysa |
| --- | --- | --- | --- |
| | Anti-HCV Next | Commercially Available Anti-HCV Assay | |
| 10000 | 53 | 53 | 0 |
| 10025 | 56 | 56 | 0 |
| 10026 | 77 | 80 | -3 |
| 10043 | 50 | NDb | N/A |
| 10062 | 41 | 41 | 0 |
| 10071 | 75 | 77 | -2 |
| 10165 | 24 | 24 | 0 |
| PHV912 | 0 | 0 | 0 |
| PHV915 | 0 | 0 | 0 |
| PHV916 | 9 | 9 | 0 |
| PHV917 | 85 | 85 | 0 |
| PHV919 | 0 | 0 | 0 |
| PHV924 | 59 | 59 | 0 |
| PHV926 | 0 | 0 | 0 |
| SCP-HCV-009 | 52 | 52 | 0 |
| SCP-HCV-011 | 27 | N/Ac | N/A |
N/A = Not Applicable
${}^{a}$ Difference in days $=$ Anti-HCV Next days to first reactive result - commercially available anti-HCV assay days to first reactive result.
b ND = No bleed of this panel was detected reactive by the commercially available anti-HCV assay.
c First reactive result for the commercially available anti-HCV assay was not continuously reactive on subsequent bleed.
The total number of seroconversion panel bleeds detected with the Anti-HCV Next assay on Alinity i was greater than or equal to the number of panels behind compared to the number detected with the commercially available anti-HCV assay.
# 7. Assay Cut-Off:
The cutoff level was set to $1.00\mathrm{S / CO}$ given by the Sample Relative Light Unit (RLU)/ cutoff RLU, where the cutoff RLU was set to be $0.18\times$ Calibrator 1 Mean RLU.
The cutoff verification by ROC analysis supports that the selected cutoff level (1.00 S/CO) is within the range to optimize specificity and sensitivity. The cutoff was validated by the clinical studies included in this submission.
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8. Accuracy (Instrument):
N/A
9. Carry-Over:
A study was conducted to evaluate the Anti-HCV Next assay (for Alinity i instrument) for its susceptibility to within-assay sample carryover. Specifically, it tested whether samples with exceptionally high levels of anti-HCV antibodies would contaminate or affect the results of other samples. The carryover effect was determined by calculating the difference in the mean Signal to Cutoff (S/CO) values between protected and unprotected samples.
Anti-HCV Next for Alinity i Within-Assay Sample Carryover
| Protected Sample | | | Unprotected Sample | | | Difference^{a} | | % Difference^{b} | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| N | Mean (S/CO) | SD | N | Mean (S/CO) | SD | Result (S/CO) | Two-Sided 95% CI | Result | Two-Sided 95% CI |
| 12 | 0.79 | 0.014 | 12 | 0.77 | 0.025 | -0.01 | (-0.03, 0.01) | -1.4 | (-3.6, 0.8) |
a Difference = Unprotected sample mean (S/CO) - Protected sample mean (S/CO)
b %Difference = (Difference / Protected sample mean) x 100
The results indicate that there is no significant carryover effect within the assay.
10. Genotype Detection
A total of 149 HCV specimens from genotypes 1 through 6 (including genotype 4 non-a subtype) were evaluated using the Anti-HCV Next assay on the Alinity i system.
All specimens were reactive with the Anti-HCV Next assay.
| Genotype | n |
| --- | --- |
| Genotype 1 | 59 |
| Genotype 2 | 23 |
| Genotype 3 | 25 |
| Genotype 4 | 21 |
| Genotype 4 non-a subtype | 5 |
| Genotype 5 | 8 |
| Genotype 6 | 8 |
B Comparison Studies:
1. Method Comparison with Predicate Device:
See Clinical Studies section.
2. Matrix Comparison:
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The study's purpose was to evaluate the suitability of eleven different blood collection tube types against a control serum tube for use with the Abbott Alinity i Anti-HCV Next assay.
Matched donor sets consisting of the different tube types were obtained from 12 individual donors and individual positive samples were used to prepare low positive analyte level samples.
The analysis of 1,074 valid replicates demonstrated that for all evaluation tube types the mean percent difference for low-positive samples ranged from 0.1% to 2.0%, and the mean difference for negative samples was 0.00 S/CO.
The study demonstrated that the following blood collection tube types are acceptable for use with the Alinity i Anti-HCV Next assay:
- Serum
- Serum (Separator Tube)
- Dipotassium EDTA (including plasma separator tube)
- Tripotassium EDTA
- Lithium Heparin (including separator tube)
- Sodium Heparin
- Sodium Citrate
- Citrate Phosphate Dextrose (CPD)
- Citrate Phosphate Dextrose Adenine-1 (CPDA-1)
- Disodium EDTA
## C Clinical Studies:
1. Clinical Sensitivity:
N/A
2. Clinical Specificity:
N/A
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
A clinical study was conducted to evaluate the performance of the Alinity i Anti-HCV Next assay. The study involved testing 3,732 prospectively collected specimens from various patient populations, including individuals at risk for HCV infection, those with signs and symptoms of hepatitis, and pregnant women.
The performance of Anti-HCV Next was evaluated against a final HCV infection status that includes results from FDA approved anti-HCV assays and HCV RNA assay.
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The Positive percent agreement (PPA) and Negative percent agreement (NPA) of Alinity i Anti-HCV Next assay are shown in the following table.
| Specimen Category | Number Tested | HCV Status | | | | | | PPA (%) (95% CI) | NPA (%) (95% CI) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | HCV Infected | | Indeterminate | | HCV Not Infected | | | |
| | | R | NR | R | NR | R | NR | | |
| Individuals at Risk for HCV Infection | 1584 | 232 | 2 | 2 | 0 | 49 | 1299 | 99.15 (232/234) (96.94, 99.77) | 96.22 (1299/1350) (95.07, 97.12) |
| Individuals with Signs and Symptoms of Hepatitis | 1898 | 155 | 0 | 2 | 0 | 31 | 1710 | 100.00 (155/155) (97.58, 100.00) | 98.11 (1710/1743) (97.35, 98.65) |
| Pregnant Females | 250 | 11 | 0 | 0 | 0 | 8 | 231 | 100.00 (11/11) (74.12, 100.00) | 96.65 (231/239) (93.54, 98.29) |
| Overall | 3732 | 398 | 2 | 4 | 0 | 88 | 3240 | 99.50 (398/400) (98.20, 99.86) | 97.24 (3240/3332) (96.63, 97.74) |
R = Reactive; NR = Nonreactive; PPA = Positive Percent Agreement; NPA = Negative Percent Agreement; CI = Confidence Interval,
## Overall Agreement:
Positive Percent Agreement (PPA): 99.50% (398/400)
Negative Percent Agreement (NPA): 97.24% (3,240/3,332)
## D Clinical Cut-Off:
N/A
## E Expected Values/Reference Range:
### A. Expected Values
Representative performance data are provided in this section. Results obtained in individual laboratories may vary.
It is recommended that each laboratory determines its own reference range based upon its particular locale and population characteristics.
Of the 3732 specimens tested in the Anti-HCV Next clinical study, 1898 (50.9%) were from individuals with signs and symptoms of hepatitis, 1584 (42.4%) were from individuals at risk for HCV infection, and 250 (6.7%) were from pregnant females. Testing of these specimens was performed at 3 clinical sites located in Charleston, SC; Temple, TX; and Baltimore, MD.
## F Other Supportive Instrument Performance Characteristics Data:
N/A
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VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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