← Product Code [MZP](/submissions/MI/subpart-d%E2%80%94serological-reagents/MZP) · K252102

# Alinity m HCV (K252102)

_Abbott Molecular, Inc. · MZP · Sep 25, 2025 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MZP/K252102

## Device Facts

- **Applicant:** Abbott Molecular, Inc.
- **Product Code:** [MZP](/submissions/MI/subpart-d%E2%80%94serological-reagents/MZP.md)
- **Decision Date:** Sep 25, 2025
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.3170
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The Alinity m HCV assay is an in vitro reverse transcription-polymerase chain reaction (RT-PCR) assay for both the detection and quantitation of hepatitis C virus (HCV) RNA, in human plasma (EDTA, Acid Citrate Dextrose) or serum, from HCV antibody positive individuals. The assay is intended for use as an aid in the diagnosis of active HCV infection in individuals with antibody evidence of HCV infection, and to aid in the management of patients with known active HCV infection, including Sustained Virologic Response (SVR) determination. The results from the Alinity m HCV assay must be interpreted within the context of all relevant clinical and laboratory findings. The Alinity m HCV assay is not intended to be used in screening blood, plasma, serum, tissue or tissue donors for HCV.

## Device Story

Alinity m HCV is an automated in vitro RT-PCR assay for detection and quantitation of HCV RNA in human plasma or serum. The device uses magnetic microparticle technology for automated nucleic acid extraction, followed by real-time PCR amplification and fluorescence detection. It requires three specific kits: AMP (amplification/detection reagents), CTRL (controls), and CAL (calibrators). The system is a random-access analyzer; it processes samples, calibrators, and controls automatically. The device is used in clinical laboratory settings by trained personnel. Output is a quantitative HCV RNA concentration, which clinicians use to diagnose active infection and monitor patient response to therapy (SVR). The subject device introduces alternative DNA polymerase and reverse transcriptase enzymes compared to the predicate, with no changes to sample processing or data reduction.

## Clinical Evidence

Bench testing only. Studies included Limit of Detection (98.6% detection at 12 IU/mL), linearity (12 to 100,000,000 IU/mL), precision (within-lab SD ≤ 0.25 Log IU/mL for 100-200M IU/mL; ≤ 0.35 Log IU/mL for 12-36 IU/mL), and method comparison (Deming regression slope 1.01, r=0.996, mean bias 0.06 Log IU/mL). Reproducibility was evaluated across 3 sites.

## Technological Characteristics

In vitro RT-PCR assay; utilizes magnetic microparticle technology for nucleic acid extraction. Reagents include enzymes (alternative DNA polymerase/reverse transcriptase), primers, probes, and Uracil-DNA Glycosylase (UDG) for contamination control. Operates on the Alinity m System (automated analyzer). Connectivity: Integrated system. Storage: 2°C to 8°C (AMP kit), -25°C to -15°C (CTRL/CAL kits).

## Regulatory Identification

A nucleic acid-based hepatitis C virus (HCV) ribonucleic acid (RNA) test is identified as an in vitro diagnostic device intended for prescription use as an aid in the diagnosis of HCV infection in specified populations, and/or as an aid in the management of HCV-infected patients including guiding the selection of genotype-specific treatment in individuals with chronic HCV infection. The test is intended for use with human serum or plasma. The test is not intended for use as a donor screening test for the presence of HCV antibodies in blood, blood products, or tissue donors.

## Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) For all nucleic acid-based HCV RNA tests, the labeling required under § 809.10(b) of this chapter must include:
(i) A prominent statement that the test is not intended for use as a donor screening test for the presence of HCV RNA from human cells, tissues, and cellular and tissue-based products.
(ii) A detailed explanation of the principles of operation and procedures for performing the assay.
(iii) A detailed explanation of the interpretation of results.
(iv) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. These limitations must include, but are not limited to, statements that indicate:
(A) The specimen types for which the device has been cleared and that use of this test kit with specimen types other than those specifically cleared for this device may result in inaccurate test results.
(B) When applicable, that assay performance characteristics have not been established in populations of immunocompromised or immunosuppressed patients or, other populations where test performance may be affected.
(C) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results.
(2) For all nucleic acid-based HCV RNA tests, the design verification and validation must include:
(i) Detailed device description, including the device components, ancillary reagents required but not provided, and an explanation of the device methodology. Additional information appropriate to the technology must be included such as design of primers and probes, rationale for the selected gene targets, specifications for amplicon size, and degree of nucleic acid sequence conservation.
(ii) For devices with assay calibrators, the design and nature of all primary, secondary, and subsequent quantitation standards used for calibration as well as their traceability to a standardized reference material that FDA has determined is appropriate (
*e.g.,* a recognized consensus standard). In addition, analytical testing must be performed following the release of a new lot of the standard material that was used for device clearance or approval, or when there is a transition to a new calibration standard.(iii) Documentation and characterization (
*e.g.,* determination of the identity, supplier, purity, and stability) of all critical reagents (including nucleic acid sequences for primers and probes) and protocols for maintaining product integrity.(iv) Detailed documentation of analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including, but not limited to, limit of detection (LoD), upper and lower limits of quantitation (ULoQ and LLoQ, respectively), linearity, precision, endogenous and exogenous interferences, cross reactivity, carryover, matrix equivalency, and sample and reagent stability. Samples selected for use in analytical studies or used to prepare samples for use in analytical studies must be from subjects with clinically relevant circulating genotypes in the United States. Cross-reactivity studies must include samples from HCV RNA negative subjects with other causes of liver disease, including autoimmune hepatitis, alcoholic liver disease, chronic hepatitis B virus, primary biliary cirrhosis, and nonalcoholic steatohepatitis, when applicable. The effect of each claimed nucleic-acid isolation and purification procedure on detection must be evaluated.
(v) 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.
(vi) 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.
(vii) Multisite reproducibility study that includes the testing of three independent production lots.
(viii) All stability protocols, including acceptance criteria.
(ix) Final release test results for each lot used in clinical studies.
(x) Analytical sensitivity and specificity of the test must be the same or better than that of other cleared or approved tests.
(xi) Lot-to-lot precision studies, as appropriate.
(3) For devices intended for the qualitative detection of HCV RNA, in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, the design verification and validation must include detailed documentation of performance from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved qualitative HCV RNA test, or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with appropriate numbers of HCV positive and negative samples in applicable risk categories. Additional genotypes must be validated using appropriate numbers and types of samples. The samples may be a combination of fresh and repository samples, sourced from within and outside the United States, as appropriate. The study designs, including number of samples tested, must be sufficient to meet the following criteria:
(i) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 95 percent.
(ii) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 96 percent.
(4) For devices intended for the quantitative detection of HCV RNA, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply:
(i) Labeling required under § 809.10(b) of this chapter must include a prominent statement that the test is not intended as a diagnostic test to confirm the presence of active HCV infection, when applicable.
(ii) Design verification and validation must include the following:
(A) Detailed documentation of the following analytical performance studies conducted as appropriate to the technology, specimen types tested, and intended use of the device, including but not limited to: LoD, ULoQ and LLoQ. LoD, LLoQ, and linearity studies must demonstrate acceptable device performance with all HCV genotypes detected by the device.
(B) Detailed documentation of clinical performance testing from either:
(
*1* ) A multisite clinical study with an appropriate number of clinical samples from chronically HCV infected patients in which the results are compared to an FDA-cleared or approved quantitative HCV RNA test, or a comparator that FDA has determined is appropriate. This study must include a sufficient number of HCV positive samples containing an analyte concentration near the LLoQ to describe performance at this level. Clinical samples must cover the full range of the device output and must be consistent with the distribution of these genotypes in the U.S. population. Clinical samples may be supplemented with diluted clinical samples for those viral load concentrations that are not sufficiently covered by natural clinical specimens, or(
*2* ) A clinical study with prospectively collected samples demonstrating clinical validity of the device.(C) Detailed documentation of a qualitative analysis near the lower end of the measuring range demonstrating acceptable performance when used as an aid in diagnosis.
(5) For devices intended for HCV RNA genotyping, in addition to the special controls listed in paragraphs (b)(1) and (2) of this section, design verification and validation must include the following:
(i) Detailed documentation of an analytical performance study demonstrating the LoD for all HCV genotypes detected by the device.
(ii) Detailed documentation, including results, of a multisite clinical study that assesses genotyping accuracy (
*i.e.,* the proportion of interpretable results that match with the reference method result) and the genotyping rate (*i.e.,* the proportion of results that were interpretable).(6) For any nucleic acid-based HCV RNA 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

- Alinity m HCV ([P190025](/device/P190025.md))

## 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

K252102

B Applicant

Abbott Molecular Inc.

C Proprietary and Established Names

Alinity m HCV

D Regulatory Information

|  Product Code(s) | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  MZP | Class II | 21 CFR 866.3170 - Nucleic Acid-Based Hepatitis C Virus Ribonucleic Acid Tests | MI - Microbiology  |

## II Submission/Device Overview:

A Purpose for Submission:

To obtain clearance for the modification of a previously approved device, Alinity m HCV assay, which allows the use of an alternative DNA polymerase and reverse transcriptase.

B Measurand:

Hepatitis C virus (HCV) RNA.

C Type of Test:

Quantitative in vitro reverse transcription-polymerase chain reaction (RT-PCR) assay.

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 Alinity m HCV assay is an in vitro reverse transcription-polymerase chain reaction (RT-PCR) assay for both the detection and quantitation of hepatitis C virus (HCV) RNA, in human plasma (EDTA, Acid Citrate Dextrose) or serum, from HCV antibody positive individuals. The assay is intended for use as an aid in the diagnosis of active HCV infection in individuals with antibody evidence of HCV infection, and to aid in the management of patients with known active HCV infection, including Sustained Virologic Response (SVR) determination.

The results from the Alinity m HCV assay must be interpreted within the context of all relevant clinical and laboratory findings.

The Alinity m HCV assay is not intended to be used in screening blood, plasma, serum, tissue or tissue donors for HCV.

B Indication(s) for Use:
See Intended Use above.

C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only

D Special Instrument Requirements:
For use with the Alinity m System.

IV Device/System Characteristics:

A Device Description:
The Alinity m HCV assay is an in vitro reverse transcription-polymerase chain reaction (RT-PCR) assay for both the detection and quantitation of hepatitis C virus (HCV) RNA, in human plasma (EDTA, Acid Citrate Dextrose) or serum, from HCV antibody positive individuals. The assay is intended for use as an aid in the diagnosis of active HCV infection in individuals with antibody evidence of HCV infection, and to aid in the management of patients with known active HCV infection, including Sustained Virologic Response (SVR) determination.

The Alinity m HCV assay requires 3 separate assay specific kits:
- Alinity m HCV AMP Kit
- Alinity m CMV CTRL Kit
- Alinity m CMV CAL Kit

B Principle of Operation:
The Alinity m HCV assay utilizes RT-PCR with fluorescence labeled probes to amplify and detect HCV RNA genomic sequences that have been extracted from human plasma or serum specimens. The steps of the Alinity m HCV assay consist of sample preparation, RT-PCR assembly, amplification, detection, and result calculation and reporting. All steps of the Alinity m HCV assay procedures are executed automatically by the Alinity m System. Manual dilutions

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may be performed for low-volume specimens to meet the minimum volume requirement, and for high-titer specimens above the upper limit of quantitation (ULoQ).

The Alinity m System is designed to be a random access analyzer that can perform the Alinity m HCV assay in parallel with other Alinity m assays on the same instrument.

HCV RNA from human plasma or serum is extracted automatically on-board in the Alinity m System using the Alinity m Sample Prep Kit 2, Alinity m Lysis Solution, and Alinity m Diluent Solution. The Alinity m System employs magnetic microparticle technology to facilitate nucleic acid capture, wash, and elution. The resulting purified nucleic acids are then combined with liquid unit-dose Alinity m HCV activation reagent and lyophilized unit-dose Alinity m HCV amplification/detection reagents and transferred into a reaction vessel. Alinity m Vapor Barrier Solution is then added to the reaction vessel which is then transferred to an amplification/detection unit for reverse transcription, PCR amplification, and real-time fluorescence detection of HCV targets.

At the beginning of the Alinity m HCV sample preparation process, a lyophilized unit-dose IC on the AMP Tray is rehydrated by the Alinity m System and delivered into each sample preparation reaction. The IC is then processed through the entire sample preparation and real-time PCR procedure along with the specimens, calibrators, and controls to demonstrate proper sample processing and validity.

The Alinity m HCV amplification/detection reagents consist of enzymes, primers, probes, and activation reagents that enable reverse transcription, polymerization, and detection. The Alinity m HCV amplification/detection reagent also contains Uracil-DNA Glycosylase (UDG) as a contamination control for amplicons containing uracil, which may be present in molecular laboratories.

An HCV calibration curve is required for determination of HCV RNA concentration. Two levels of calibrators are processed through sample preparation and RT-PCR to generate the calibration curve. The concentration of HCV RNA in specimens and controls is then calculated from the stored calibration curve.

Assay controls are tested at or above an established minimum frequency to help ensure that instrument and reagent performance remains satisfactory. During each control event, a negative control, a low-positive control, and a high-positive control are processed through sample preparation and RT-PCR procedures that are identical to those used for specimens.

## Calculation

Quantitative viral load results are reported for patient specimens with HCV viral concentrations within the assay's quantitation range. The concentration of HCV RNA in a specimen is calculated from the calibration curve by the system software. The Alinity m System reports the results in International Units as IU/mL or Log [IU/mL]. Refer to the Alinity m System Operations Manual for configuration of result units. For specimens tested with the Specimen Dilution Procedure, the Alinity m System calculates and reports the neat concentration (ie, prior to dilution), by using the dilution factor selected by the user.

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# Results and Interpretation

## Alinity M System Report

## User Performed

|  Result | Interpretation | Interpretation Additional Information | Clinical Interpretation  |
| --- | --- | --- | --- |
|  Not Detected | HCV RNA not detected |  | No active HCV infection. For HCV Diagnosis: No further testing indicated. For Viral Load Assessment: Routine clinical follow-up according to national HCV guidelines.  |
|  <LLoQ | HCV RNA detected but not quantified | HCV RNA concentration is below the Lower Limit of Quantitation (LLOQ) of the assay (12 IU/mL). | Low level HCV viremia may indicate previous spontaneous or treatment-related resolution of HCV infection. For HCV Diagnosis: Results must be interpreted within the context of all relevant clinical and laboratory findings. For Viral Load Assessment: Routine clinical follow-up according to national HCV guidelines.  |
|  12 to <25 IU/mL (1.08 to <1.40 Log IU/mL) | HCV RNA detected and quantified | HCV RNA concentration is within the linear range of the assay (≥12 IU/mL and <25 IU/mL). | Low level HCV viremia may indicate previous spontaneous or treatment-related resolution of HCV infection. For HCV Diagnosis and Viral Load Assessment: Provide patient with appropriate counseling and link to care and treatment according to current national HCV treatment guidelines.  |
|  25 IU/mL to ≤ULOQ (1.40 Log IU/mL to ≤ULOQ) | HCV RNA detected and quantified | HCV RNA concentration is within the linear range of the assay (≥25 IU/mL to ≤ULOQ). | Active HCV infection. For HCV Diagnosis and Viral Load Assessment: Provide patient with appropriate counseling and link to care and treatment according to current national HCV treatment guidelines.  |
|  >ULoQ | HCV RNA detected | HCV RNA concentration is above the Upper Limit of Quantitation (ULOQ) of the assay. | Active HCV infection. For HCV Diagnosis and Viral Load Assessment: Provide patient with appropriate counseling and link to care and treatment according to current national HCV treatment guidelines.  |

## C Instrument Description Information:

1.  **Instrument Name:**
Alinity m System

2.  **Specimen Identification:**
Hepatitis C virus (HCV) RNA in human plasma (EDTA, Acid Citrate Dextrose) or serum, from HCV antibody positive individuals.

3.  **Specimen Sampling and Handling:**
For the Alinity m HCV assay, only use collection tubes as described: Plasma including Acid Citrate Dextrose (ACD), K₂ EDTA, K₃ EDTA, Plasma Preparation Tube (PPT), and serum including serum separator tubes (SST) and serum rapid-clot tubes.

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4. Calibration:

Alinity m HCV CAL Kit consists of 2 calibrator levels, each supplied as liquid in single-use tubes.

5. Quality Control:

Alinity m HCV CTRL Kit consisting of negative controls, low-positive controls, and high-positive controls, each supplied as liquid in single-use tubes.

V Substantial Equivalence Information:

A Predicate Device Name(s):

Alinity m HCV

B Predicate 510(k) Number(s):

P190025

C Comparison with Predicate(s):

|  Device & Predicate Device(s): | P190025 | K252102  |
| --- | --- | --- |
|  Device Trade Name | Alinity m HCV | Alinity m HCV  |
|  Regulation No./Product Code | 21 CFR 814 / MZP | 21 CFR 866.3170 / MZP  |
|  Device Class | Class III | Class II  |
|  General Device Characteristic Similarities |  |   |
|  Intended Use/Indications For Use | The Alinity m HCV assay is an in vitro reverse transcription-polymerase chain reaction (RT-PCR) assay for both the detection and quantitation of hepatitis C virus (HCV) RNA, in human plasma (EDTA, Acid Citrate Dextrose) or serum, from HCV antibody positive individuals. The assay is intended for use as an aid in the diagnosis of active HCV infection in individuals with antibody evidence of HCV infection, and to aid in the management of patients with known active HCV infection, including Sustained Virologic Response (SVR) determination. The results from the Alinity m HCV assay must be interpreted within the context of all relevant clinical and laboratory findings. | Same  |

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|   | The Alinity m HCV assay is not intended to be used in screening blood, plasma, serum, tissue or tissue donors for HCV. |   |
| --- | --- | --- |
|  Assay Type | Quantitative | Same  |
|  Assay Target | A highly conserved sequence within the 5' untranslated region (5'utr) of the HCV genome | Same  |
|  Specimen Types | Human Plasma (EDTA, Acid Citrate Dextrose) or Serum | Same  |
|  Specimen Collection and Transport | The following blood collection tubes may be used:
**Plasma**
• K_{2} EDTA
• K_{3} EDTA
• Acid Citrate Dextrose (ACD)
• Plasma Preparation Tube (PPT)
**Serum**
• Serum Tubes
• Serum Separator Tubes (SST)
• Serum Rapid-Clot Tubes
**Plasma or Serum may be stored in:**
• Primary tubes (with or without gel) | Same  |
|  Principles of the Procedure | See above for description of principles of procedure | Same  |
|  Instrument and System Components | Alinity m System: Fully integrated and automated diagnostics analyzer which utilizes real-time PCR technology | Same  |
|  Sample Preparation Instrument Components | Automated liquid handling and robotic manipulation platform | Same  |
|  Assay Controls | • Negative Control
• Low Positive Control
• High Positive Control
• Internal Control (IC) | Same  |
|  Results Reporting | • Not Detected
• Detected < LLoQ
• Detected > ULoQ
• Concentration from LLoQ to ≤ ULoQ, reported in IU/mL or Log IU/mL
For low volume specimens tested with the Specimen Dilution Procedure, quantitative | Same  |

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|   | results generated on the Alinity m System represent the HCV RNA concentration in the specimen prior to dilution. |   |
| --- | --- | --- |
|  Reagents and Storage Conditions | Alinity m HCV AMP Kit: 2°C to 8°C
Alinity m HCV CTRL Kit: –25°C to –15°C
Alinity m HCV CAL Kit: –25°C to –15°C | Same  |
|  General Device Characteristic Differences |  |   |
|  Amplification Enzymes | Original DNA Polymerase is the enzyme used for DNA amplification. Original Reverse Transcriptase is the enzyme that converts the target RNA to complimentary DNA (cDNA). | Original DNA Polymerase or alternative DNA polymerase is the enzyme used for DNA amplification. Original Reverse Transcriptase or alternative Reverse Transcriptase is the enzyme that converts the target RNA to complimentary DNA (cDNA).  |

VI Standards/Guidance Documents Referenced:

1. Special Control (86 FR 66169), labeling requirements under 21 CFR 809.10(b), the information for special controls pertaining to Nucleic Acid-Based Hepatitis C Virus Ribonucleic Acid Tests (21 CFR 866.3170).
2. CLSI EP05-A3: Clinical Laboratory Standards Institute. Evaluation of the Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition. CLSI Guideline EP05-A3, CLSI: Wayne, PA, 2014.
3. CLSI EP35: Clinical Laboratory Standards Institute. Assessment of Equivalence or Suitability of Specimen Types for Medical Laboratory Measurement Procedures; Approved Guideline – First Edition. CLSI Guideline EP35. CLSI: Wayne, PA: 2019.
4. CLSI EP09c: Clinical and Laboratory Standards Institute. Measurement Procedure Comparison and Bias Estimation Using Patient Sample – Third Edition. CLSI Guideline EP09c. Wayne, PA: CLSI; 2018.
5. CLSI EP06: Clinical Laboratory Standards Institute. Evaluation of Linearity of Quantitative Measurement Procedures; Approved Guideline – Second Edition. CLSI Guideline EP06, CLSI: Wayne, PA, 2020.
6. CLSI EP17-A2: Clinical Laboratory Standards Institute. Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline – Second Edition. CLSI Guideline EP17-A2, CLSI: Wayne, PA, 2012.

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# VII Performance Characteristics (if/when applicable):

# A Analytical Performance:

# 1. Precision/Reproducibility:

# Precision:

Precision of Alinity m HCV assay with alternative reverse transcriptase and DNA polymerase was determined by testing 8 panel members with HCV concentrations that span the range of approximately  $12\mathrm{IU / mL}$  to 200,000,000 IU/mL (1.08 to 8.30 Log IU/mL). A high titer specimen and an HCV Armored RNA stock representing the most common HCV genotype (Genotype 1) and a second non-1 genotype (Genotype 2), were used to prepare panel members in negative human plasma. Each panel member was tested in 3 replicates, twice each day for 15 days on 1 Alinity m system operated by 3 operators using 3 lots of HCV AMP kit, for a total of 270 replicates per panel member. The study design and analysis were derived from recommendations in CLSI Guideline EP05-A3,  $3^{\mathrm{rd}}$  Edition.

The precision study results are shown in Table 1.

Table 1. Precision Analysis (All lots)

|  Panel | N | Mean Conc. (Log IU/mL) | Within-Run |   | Between-Run |   | Between-Day |   | Within-Laboratorya |   | Between-Lot |   | Totalb  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  |  | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV  |
|  01 | 269 | 0.96 | 0.24 | 24.6 | 0.00 | 0.00 | 0.10 | 10.2 | 0.26 | 26.6 | 0.09 | 9.1 | 0.27 | 28.2  |
|  02 | 270 | 1.61 | 0.14 | 8.8 | 0.06 | 3.5 | 0.00 | 0.0 | 0.15 | 9.5 | 0.08 | 4.8 | 0.17 | 10.6  |
|  03 | 270 | 1.80 | 0.11 | 6.2 | 0.06 | 3.1 | 0.00 | 0.0 | 0.13 | 7.0 | 0.07 | 4.1 | 0.15 | 8.1  |
|  04 | 270 | 2.88 | 0.09 | 3.0 | 0.05 | 1.6 | 0.00 | 0.0 | 0.10 | 3.4 | 0.07 | 2.3 | 0.12 | 4.1  |
|  05 | 270 | 3.78 | 0.07 | 1.9 | 0.04 | 1.1 | 0.00 | 0.0 | 0.08 | 2.2 | 0.06 | 1.6 | 0.10 | 2.7  |
|  06 | 270 | 5.85 | 0.06 | 1.1 | 0.02 | 0.3 | 0.03 | 0.5 | 0.07 | 1.2 | 0.05 | 0.9 | 0.09 | 1.5  |
|  07 | 270 | 6.89 | 0.04 | 0.5 | 0.02 | 0.2 | 0.00 | 0.0 | 0.04 | 0.6 | 0.06 | 0.9 | 0.07 | 1.1  |
|  08 | 270 | 8.26 | 0.04 | 0.5 | 0.01 | 0.1 | 0.02 | 0.2 | 0.05 | 0.6 | 0.10 | 1.2 | 0.11 | 1.3  |

aWithin-Laboratory includes Within-Run, Between-Run, and Between-Day Components.
bTotal includes Within-Run, Between-Run, Between-Day, and Between-Lot Components.

# Reproducibility:

Reproducibility of Alinity m HCV assay with alternative reverse transcriptase and DNA polymerase was determined by testing 10 panel members with HCV concentrations that span the range of approximately  $12\mathrm{IU / mL}$  (the assay LLoQ) to 100,000,000 IU/mL and one HCV negative member, using 1 lot, 3 external sites, 1 instrument per site, 5 days, 2 runs per day, and 4 replicates per run. HCV genotype 1a and genotype 2 were used for the reproducibility study. The study design and analysis were derived from recommendations in CLSI Guideline EP05-A3,  $3^{\mathrm{rd}}$  Edition.

The reproducibility results are summarized in Table 2.

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Table 2. Reproducibility for Positive Panel Members

|  Panel | Genotype | N | Mean Conc. (Log IU/mL) | Within-Run |   | Between-Run |   | Between-Day |   | Within-Laboratory|   | Between-site |   | Total^{}[]  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|   |  |  |  | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV  |
|  1 | 1a | 118 | 7.71 | 0.20 | 2.6 | 0.08 | 1.1 | 0.10 | 1.4 | 0.24 | 3.1 | 0.06 | 0.8 | 0.25 | 3.2  |
|  2 | 1a | 115 | 5.72 | 0.06 | 1.1 | 0.05 | 0.8 | 0.00 | 0.0 | 0.08 | 1.4 | 0.06 | 1.1 | 0.10 | 1.8  |
|  3 | 1a | 115 | 3.53 | 0.06 | 1.6 | 0.04 | 1.1 | 0.03 | 0.9 | 0.08 | 2.2 | 0.03 | 0.9 | 0.08 | 2.4  |
|  4 | 1a | 119 | 1.84 | 0.11 | 5.9 | 0.07 | 4.1 | 0.00 | 0.0 | 0.13 | 7.2 | 0.06 | 3.0 | 0.14 | 7.8  |
|  5 | 1a | 116 | 0.89 | 0.21 | 23.8 | 0.07 | 7.4 | 0.01 | 1.4 | 0.22 | 24.9 | 0.10 | 11.5 | 0.24 | 27.5  |
|  6 | 1a | 116 | 0.80 | 0.25 | 31.5 | 0.04 | 5.5 | 0.00 | 0.0 | 0.26 | 31.9 | 0.06 | 8.1 | 0.26 | 32.9  |
|  7 | 2 | 120 | 6.97 | 0.06 | 0.9 | 0.03 | 0.5 | 0.05 | 0.6 | 0.08 | 1.2 | 0.02 | 0.3 | 0.09 | 1.3  |
|  8 | 2 | 116 | 2.99 | 0.08 | 2.6 | 0.02 | 0.8 | 0.03 | 1.1 | 0.09 | 2.9 | 0.03 | 0.8 | 0.09 | 3.0  |
|  9 | 2 | 118 | 1.65 | 0.14 | 8.5 | 0.00 | 0.0 | 0.05 | 2.8 | 0.15 | 9.0 | 0.06 | 3.7 | 0.16 | 9.7  |
|  10 | 2 | 119 | 1.05 | 0.22 | 21.3 | 0.00 | 0.0 | 0.06 | 5.9 | 0.23 | 22.1 | 0.07 | 6.5 | 0.24 | 23.1  |

aWithin-Laboratory includes Within-Run, Between-Run, and Between-Day Components.
bTotal includes Within-Run, Between-Run, Between-Day, and Between-Site Components.

For the negative panel member, the overall negative percent agreement with the expected result was  $100.0\%$  (120/120) All three external sites had  $100.0\%$  negative percent agreement with the expected results.

# 2. Linearity:

Linearity was evaluated by testing 12 panel members that spanned the intended dynamic range of the assay (12 to 100,000,000 IU/mL), including a member below the expected Lower Limit of Quantification (LLoQ) at 10 IU/mL, and a member exceeding the expected Upper Limit of Quantification (ULoQ) at 200,000,000 IU/mL. Panels with different specimen types were designed to have at least 2 Log IU/mL overlap with adjacent sample types. Linearity study design and evaluation were based on the recommendations in CLSI EP06. The study was conducted using 1 lot of Alinity m HCV on 1 instrument with a minimum of 24 replicates for each panel member.

Alinity m HCV was linear across the quantitative range from 12 to 100,000,000 IU/mL (1.08 to 8.00 Log IU/mL). Results for the Alinity m HCV linearity performance are shown in Figure 1.

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![img-0.jpeg](img-0.jpeg)
Figure 1. Alinity m HCV Linearity

3. Analytical Specificity/Interference:

Refer to P190025.

4. Assay Reportable Range:

Refer to P190025. The analytical measuring interval of the Alinity m HCV assay is from the lower limit of quantitation (LLoQ) of 12 IU/mL (1.08 Log IU/mL) to the upper limit of quantitation (ULoQ) of 100,000,000 IU/mL (7.00 Log IU/mL).

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

Traceability to internation standard material:

Refer to P190025.

Reagent Stability:

The data submitted support the following storage conditions for the Alinity m HCV assay with alternative DNA polymerase and alternative reverse transcriptase.

Table 3. Alinity m HCV AMP kit stability

|  Stability Study | Expiration  |
| --- | --- |
|  Reagent On-board | 30 days  |
|  Reagent Shelf-life | 18 months  |

6. Detection Limit:

The limit of detection (LoD) was assessed by testing dilutions of the international standard material for HCV RNA (code 18/184) prepared in HCV-negative human plasma. The three

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concentration panel members (9.0 IU/mL, 12.0 IU/mL, and 16.0 IU/mL) were selected based on LoD of the on-market Alinity m HCV (12 IU/mL). Testing for each HCV RNA concentration was performed with 3 lots of reagents across multiple days. LoD study design and analysis follow CLSI EP17-A2 and demonstrate a detection rate of ≥ 95.0% for samples at the claimed LoD of 12.0 IU/mL (1.08 Log IU/mL) and above.

7. Lower Limit of Quantitation (LLoQ):

LLoQ is defined as the lowest concentration at which HCV RNA is reliably quantitated within an acceptable total error. The LLoQ was evaluated based on the recommendation in CLSI EP17-A2. Total Analytical Error (TAE) and Total Error in difference between two measurements (TE) were calculated for each HCV panel members from the LoD study, Linearity study and Precision study at the LLoQ claim concentrations of 12 IU/mL, as well as panel members higher and lower than the claimed LoD.

The results are presented in Table 4.

Table 4. Alinity m HCV TAE and TE (overall)
|  Study | Panel | N | Target (IU/mL) | Target (Log IU/mL) | Mean (Log IU/mL) | Bias (Log IU/mL) | SD | TAE | TE  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Linearity | 11 | 24 | 12 | 1.08 | 0.90 | -0.18 | 0.27 | 0.72 | 0.76  |
|   | 12 | 24 | 10 | 1.00 | 0.72 | -0.28 | 0.32 | 0.93 | 0.92  |
|  Precision | 01 | 269 | 12 | 1.08 | 0.96 | -0.12 | 0.26 | 0.63 | 0.73  |
|  LoD | 1 | 138 | 9 | 0.95 | 0.77 | -0.18 | 0.26 | 0.70 | 0.74  |
|   | 2 | 141 | 12 | 1.08 | 0.85 | -0.23 | 0.27 | 0.77 | 0.76  |
|   | 3 | 140 | 16 | 1.20 | 1.06 | -0.15 | 0.21 | 0.57 | 0.59  |

The panel members with the target concentration at the assay's LLoQ of 12 IU/mL (1.08 Log IU/mL) have TAE and TE less than or equal to 1.00 Log IU/mL.

8. Accuracy (Instrument):

Refer to P190025.

9. Carry-Over:

Refer to P190025.

B Comparison Studies:

1. Method Comparison with Predicate Device:

The Alinity m HCV clinical specimen method comparison testing was conducted at one internal testing site using 3 reagent lots of the Alinity m HCV with alternative enzymes and 1 lot of the on-market Alinity m HCV. The study used de-identified plasma and serum specimens and samples were selected such the HCV levels in the samples span the measuring range of the Alinity m HCV assay. To ensure coverage of the measuring range, clinical specimens were either tested neat or samples were created as needed by spiking individual negative clinical specimens with individual positive clinical specimens to reach the necessary target concentrations.

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Figure 2 shows the Deming regression performed using the on-market Alinity m HCV assay result as the independent variable and the respective Alinity m HCV with alternative enzymes assay result as the dependent variable on 222 clinical samples. The Deming regression analysis results have correlation coefficient (r) of 0.996, a slope of 1.01 (95% CI of 1.00, 1.02), and intercept of 0.03 (95% CI of -0.02, 0.09).

![img-1.jpeg](img-1.jpeg)
Figure 2. Deming Regression Plot – All data

Systemic Difference was calculated for selected viral load levels (1.08, 1.40, 3.60, and 5.80 Log IU/mL) along with the two-sided 95% confidence intervals (Table 5).

Table 5. Systemic Difference at Selected Viral Load Levels

|  Target Viral Load Levels | Systemic Difference | 95% CI  |
| --- | --- | --- |
|  1.08 Log IU/mL | 0.04 Log IU/mL | (-0.00, 0.09)  |
|  1.40 Log IU/mL | 0.05 Log IU/mL | (0.00, 0.09)  |
|  3.60 Log IU/mL | 0.06 Log IU/mL | (0.04, 0.09)  |
|  5.80 Log IU/mL | 0.08 Log IU/mL | (0.05, 0.11)  |

The Alinity m HCV assay with alternative DNA polymerase and alternative reverse transcriptase has viral load values with a mean bias relative to the comparator assay of less than or equal to 0.25 Log IU/mL within the quantitation range.

2. Matrix Comparison:

Refer to P190025.

C Clinical Studies:

1. Clinical Sensitivity:

Refer to P190025

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2. Clinical Specificity:

Refer to P190025

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

N/A

D. Clinical Cut-Off:

Refer to P190025.

E. Expected Values/Reference Range:

Refer to P190025.

F. Other Supportive Instrument Performance Characteristics Data:

N/A

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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**Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MZP/K252102](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/MZP/K252102)

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