The Aptima HCV Quant Dx assay is a real-time transcription-mediated amplification (TMA) test used for both detection and quantitation of hepatitis C virus (HCV) RNA in fresh and frozen human serum and plasma from HCV-infected individuals. Plasma may be prepared in ethylenediaminetetraacetic acid (EDTA), anticoagulant citrate dextrose (ACD) solution, and plasma preparation tubes (PPT). Serum may be prepared in serum tubes and serum separator tubes (SST). Specimens are tested using the Panther® system for automated specimen processing, amplification, detection, and quantitation. Specimens containing HCV genotypes 1 to 6 are validated for detection and quantitation in the assay. The Aptima HCV Quant Dx assay is indicated for use as an aid in the diagnosis of active HCV infection in the following populations: individuals with antibody evidence of HCV infection with evidence of liver disease, individuals suspected to be actively infected with HCV antibody evidence, and individuals at risk for HCV infection with antibodies to HCV. Detection of HCV RNA indicates that the virus is replicating and, therefore, is evidence of active infection. Detection of HCV RNA does not discriminate between acute and chronic states of infection. The Aptima HCV Quant Dx assay is also indicated for use as an aid in the management of HCV infected patients undergoing HCV antiviral drug therapy. The assay can be used to measure HCV RNA levels periodically prior to, during, and after treatment to determine sustained virological response (SVR) or nonsustained virological response (NSVR). Assay performance characteristics have been established for individuals infected with HCV and treated with certain direct-acting antiviral agents (DAA) regimens. No information is available on the assay's predictive value when other therapies are used. The results from the Aptima HCV Quant Dx assay must be interpreted within the context of all relevant clinical and laboratory findings. The Aptima HCV Quant Dx assay is not approved for use as a screening test for the presence of HCV RNA in blood or blood products.
Device Story
The Aptima HCV Quant Dx assay is a nucleic acid amplification test for detection and quantitation of HCV RNA (genotypes 1-6) in human serum/plasma. It utilizes real-time transcription-mediated amplification (TMA) on the automated Panther system. The process involves target capture using magnetic microparticles, TMA amplification via MMLV reverse transcriptase and T7 RNA polymerase, and real-time detection using fluorescently labeled torches. The Panther system processes samples, performs amplification/detection, and calculates viral load by comparing HCV and internal control signals to calibration data. The device is used in clinical laboratories by trained personnel. Output is a quantitative HCV RNA result used by physicians to diagnose active infection and monitor treatment response (SVR/NSVR). This submission updates the Assay Definition Module (ADM) to flag results impacted by flickering instrument LEDs and increases reagent on-board/off-board cycling from 5 to 8 times.
Clinical Evidence
No clinical data. Performance established via bench testing, including software verification and validation, and analytical studies evaluating background process control limits and reagent on-board stability. Studies confirmed that the updated software correctly flags invalid results due to hardware faults and supports 8-cycle reagent loading without impacting assay sensitivity or specificity.
Technological Characteristics
Nucleic acid amplification test using real-time TMA. Targets conserved 5' UTR of HCV genome (genotypes 1-6). Automated processing on Panther System. Reagents include amplification, enzyme, promoter, and target capture components. Software-controlled background process limits and reagent cycling (8 cycles). Standardized against 2nd WHO International Standard (NIBSC 96/798).
Indications for Use
Indicated for individuals with antibody evidence of HCV infection with liver disease, individuals suspected of active HCV infection, and individuals at risk for HCV infection with antibodies to HCV. Used as an aid in diagnosis of active infection and management of patients undergoing antiviral drug therapy (DAA regimens).
Regulatory Classification
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.
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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
K233352
B Applicant
Hologic, Inc.
C Proprietary and Established Names
Aptima HCV Quant Dx Assay
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:
Market clearance of Aptima HCV Quant Dx assay after modifications to the approved device (P160023). Modifications include:
- Update the Panther System Software to version 7.2.9 to incorporate:
- An update to the Assay Definition Module (ADM) to version 5.3.5.1 to implement new background minimum limits (Detect, flag and invalidate results impacted by a flickering/faulty LED lamp);
- Additional reagent on-board/off-board cycling from 5 to 8 cycles. This will facilitate operators loading reagents onto the Panther System 8 times instead of 5 times.
These changes do not introduce any changes to the original design, method of manufacture, assay procedure, principle of operation, mechanism of action, conditions of use or hardware of the Panther instrument, or to the results interpretation for the cleared assay.
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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B Measurand:
HCV RNA
C Type of Test:
Nucleic acid amplification test that uses real-time TMA technology to detect and quantitate HCV RNA
III Intended Use/Indications for Use:
A Intended Use(s):
The Aptima HCV Quant Dx assay is a real-time transcription-mediated amplification (TMA) test used for both detection and quantitation of hepatitis C virus (HCV) RNA in fresh and frozen human serum and plasma from HCV-infected individuals.
Plasma may be prepared in ethylenediaminetetraacetic acid (EDTA), anticoagulant citrate dextrose (ACD) solution, and plasma preparation tubes (PPT). Serum may be prepared in serum tubes and serum separator tubes (SST). Specimens are tested using the Panther system for automated specimen processing, amplification, detection, and quantitation. Specimens containing HCV genotypes 1 to 6 are validated for detection and quantitation in the assay.
The Aptima HCV Quant Dx assay is indicated for use as an aid in the diagnosis of active HCV infection in the following populations: individuals with antibody evidence of HCV infection with evidence of liver disease, individuals suspected to be actively infected with HCV antibody evidence, and individuals at risk for HCV infection with antibodies to HCV. Detection of HCV RNA indicates that the virus is replicating and, therefore, is evidence of active infection. Detection of HCV RNA does not discriminate between acute and chronic states of infection.
The Aptima HCV Quant Dx assay is also indicated for use as an aid in the management of HCV infected patients undergoing HCV antiviral drug therapy. The assay can be used to measure HCV RNA levels periodically prior to, during, and after treatment to determine sustained virological response (SVR) or nonsustained virological response (NSVR). Assay performance characteristics have been established for individuals infected with HCV and treated with certain direct-acting antiviral agents (DAA) regimens. No information is available on the assay's predictive value when other therapies are used. The results from the Aptima HCV Quant Dx assay must be interpreted within the context of all relevant clinical and laboratory findings.
The Aptima HCV Quant Dx assay is not approved for use as a screening test for the presence of HCV RNA in blood or blood products.
B Indication(s) for Use:
See Intended Use above
C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
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D Special Instrument Requirements:
For use with Panther System
IV Device/System Characteristics:
A Device Description:
The Aptima HCV Quant Dx assay has been designed for and validated on the Panther system. The Panther system is an integrated hardware and software system that together with the Aptima HCV Quant Dx assay fully automates all the steps necessary to perform the assay from sample preparation through amplification of nucleic acid, detection, data reduction and amplicon inactivation.
The Aptima HCV Quant Dx assay is a nucleic acid amplification test that uses real-time TMA technology to detect and quantitate HCV RNA for aiding diagnosis or to establish baseline viral load, as well as to measure on-treatment and post-treatment responses. The assay targets a conserved region of the HCV genome, detecting and quantitating genotypes 1, 2, 3, 4, 5, and 6. The assay is standardized against the 2nd WHO International Standard for Hepatitis C Virus (NIBSC Code 96/798).12.
B Principle of Operation:
The Aptima HCV Quant Dx Assay involves three main steps, which all take place in a single tube on the Panther system: target capture, target amplification by transcription-mediated amplification (TMA), and detection of the amplification products (amplicon) by the fluorescent labeled probes (torches).
During target capture, viral RNA is isolated from specimens. The specimen is treated with a detergent to solubilize the viral envelope, denature proteins, and release viral genomic RNA. Capture oligonucleotides hybridize to highly conserved regions of the HCV genome, if present, in the test specimen. The hybridized target is then captured onto magnetic microparticles that are separated from the specimen in a magnetic field. Wash steps remove extraneous components from the reaction tube.
Target amplification occurs via TMA, which is a transcription-based nucleic acid amplification method that utilizes two enzymes, MMLV (Moloney murine leukemia virus) reverse transcriptase and T7 RNA polymerase. The reverse transcriptase is used to generate a DNA copy (containing a promoter sequence for T7 RNA polymerase) of the target sequence. T7 RNA polymerase produces multiple copies of RNA amplicons from the DNA copy template. The Aptima HCV Quant Dx Assay utilizes the TMA method to amplify the 5' UTR of the HCV genome. Amplification of this region is achieved using specific primers which are designed to amplify HCV genotypes 1, 2, 3, 4, 5, and 6.
Detection is achieved using single-stranded nucleic acid torches that are present during the amplification of the target and that hybridize specifically to the amplicon in real-time. Each torch
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has a fluorophore and a quencher. When the torch is not hybridized to the amplicon, the quencher is in close proximity of the fluorophore and suppresses the fluorescence. When the torch binds to the amplicon, the quencher is moved away from the fluorophore and it will emit a signal at a specific wavelength when excited by a light source. As more torches hybridize to amplicons, a higher fluorescent signal is generated.
The time taken for the fluorescent signal to reach a specified threshold is inversely proportional to the starting HCV concentration. Each reaction has an internal calibrator/internal control (IC) that controls for variations in specimen processing, amplification, and detection. The level of HCV RNA in a sample is determined by the Panther system software using the HCV and IC signals for each reaction and comparing them to calibration information.
## Assay Components
The reagents required to perform the Aptima HCV Quant Dx assay are available in 100-test kits. The kits are packaged in 3 boxes containing 11 reagents which are required for sample processing.
Box 1: Aptima HCV Quant Dx Assay kit which contains the following reagents:
- Amplification Reagent
- Enzyme Reagent
- Promoter Reagent
- Amplification Reconstitution Reagent
- Enzyme Reconstitution Reagent
- Promoter Reconstitution Reagent
- Target Capture Reagent
Box 2: Aptima HCV Quant Dx Calibrator kit which contains the following reagent:
- Positive Calibrator
Box 3: Aptima HCV Quant Dx Controls kit which contains the following reagents:
- Negative Control
- Low Positive Control
- High Positive Control
In addition, two ancillary kits are required to run the assay:
- Panther Run Kit for Real Time Assays (for real time assays only)
- Panther System Run Kit (when running non-real time-TMA assays in parallel with real time-TMA assays)
## Interpretation of Results
The Panther system automatically determines the concentration of HCV RNA for specimens and controls by comparing the results to a calibration curve. HCV RNA concentrations are reported in IU/mL and log10 IU/mL. The interpretation of results is provided in the table below. If a 1:3 or 1:100 dilution is used for diluted specimens, the Panther system automatically calculates the HCV concentration for the neat specimen by multiplying the diluted concentration by the dilution factor and diluted specimens are flagged as diluted. Note: For diluted specimens, results listed as "Not Detected" or "< 10 Detected" may be generated by diluting a specimen with a concentration above, but close to the LoD (limit of detection) or LLoQ (lower limit of quantitation. It is recommended to collect and test another neat specimen if a quantitative result is not obtained with the diluted specimen.
K233352 - Page 4 of 11
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The Panther system does not directly provide a qualitative result (i.e., "Detected" or "Not Detected") for diagnostic use. The operator must interpret the reported HCV RNA concentration into a qualitative result as provided in Table 1.
Table 1: Aptima HCV Quant Dx assay Results Interpretation
| Reported Aptima HCV Quant Dx Result | | HCV RNA Concentration Interpretation | Clinical Interpretation |
| --- | --- | --- | --- |
| IU/mL | Log10 Valueb | | |
| Not Detected | Not Detected | HCV RNA not detecteda. Report results as “HCV not detected” | No Current HCV Infection. Follow-up testing is recommended as per national HCV guidelines for viral load assessment, and no further testing is recommended for diagnosis of HCVd. |
| <10 Detected | <1.00 | HCV RNA detected but not quantified. HCV RNA concentration is below the Lower Limit of Quantification (LLoQ) of the assay. Report results as “HCV detected, less than 10 IU/mL” | Follow-up testing is recommended as per national HCV guidelines for viral load assessment, and results must be interpreted within context of all relevant clinical and laboratory findingsd for diagnosis of HCV. |
| 10 to 25 | 1.00 to 1.40 | HCV RNA detected and quantified. HCV RNA concentration is within linear range of the assay ≥ 10 IU/mL and < 25 IU/mL. | Provide guidance for treatment and care based on current national HCV treatment guidelines for diagnosis of HCV and viral load assessment. |
| 25 to 100,000,000 | 1.40 to 8.00 | HCV RNA detected and quantified. HCV RNA concentration is within the linear range of 25 to 100,000,000IU/mL | Current HCV Infection. Provide guidance for treatment and care based on current national HCV treatment guidelines for diagnosis and viral load assessment of HCV. |
| >100,000,000 | >8.00 | HCV RNA is detected above the Upper Limit of Quantification (ULoQ). | Current HCV Infection. For HCV Diagnosis and Viral Load Assessmente Provide guidance for treatment and care based on current national HCV treatment guidelines. |
| Invalidc | Invalidc | Error indicated in generation of the result. Specimens should be retested. | N/A |
a A diagnostic interpretation should not be made from a "Not Detected" result for serum or plasma specimens that have been diluted. Obtain a new, undiluted specimen and retest.
b Value is truncated two decimal places
c Invalid results are displayed in blue-colored font.
As per CDC HCV treatment guidelines, repeat HCV RNA testing is recommended after three months for patients exposed to HCV infection within 6 months or patients with clinical evidence of HCV infection.
e Serum and Plasma specimens intended for viral load assessment with value above the ULoQ may be diluted and retested to determine a quantitative result within the linear range.
## C Instrument Description Information:
### 1. Instrument Name:
Panther System
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K233352 - Page 6 of 11
2. Specimen Identification:
A barcode reader reads the barcodes assigned to the specimen.
3. Specimen Sampling and Handling:
Fresh and frozen human serum and plasma from HCV-infected individuals. Plasma may be prepared in ethylenediaminetetraacetic acid (EDTA), anticoagulant citrate dextrose (ACD) solution, and plasma preparation tubes (PPT). Serum may be prepared in serum tubes and serum separator tubes (SST).
4. Calibration:
To generate valid results, an assay calibration must be completed. A single positive calibrator is run in triplicate each time a reagent kit is loaded on the Panther system. Once established, the calibration is valid for up to 24 hours. Software on the Panther system alerts the operator when a calibration is required. The operator scans a calibration coefficient found on the Master Lot Barcode Sheet provided with each reagent kit.
During processing, criteria for acceptance of the calibrator are automatically verified by the software on the Panther system. If less than two of the calibrator replicates are valid, the software automatically invalidates the run. Samples in an invalidated run must be retested using a freshly prepared calibrator and freshly prepared controls.
The Panther system automatically determines the concentration of HCV RNA for specimens and controls by comparing the results to a calibration curve. HCV RNA concentrations are reported in IU/mL and log10 IU/mL.
5. Quality Control:
Negative and Positive Controls:
To generate valid results, a set of assay controls must be tested. One replicate of the negative control, the low positive control, and the high positive control must be tested each time a reagent kit is loaded on the Panther system. Once established, the controls are valid for up to 24 hours. Software on the Panther system alerts the operator when controls are required. During processing, criteria for acceptance of controls are automatically verified by software on the Panther system. To generate valid results, the negative control must give a result of "Not Detected" and the positive controls must give results within predefined parameters (LPC Nominal Target: 2.36 Log10 IU/mL, HPC Nominal Target: 5.36 Log10 IU/mL). If any one of the controls has an invalid result, the software automatically invalidates the run. Samples in an invalidated run must be retested using a freshly prepared calibrator and freshly prepared controls.
Internal Calibrator/Internal Control:
Each sample contains an internal calibrator/internal control (IC). During processing, IC acceptance criteria are automatically verified by the Panther system software. If an IC result is invalid, the sample result is invalidated. Every sample with an invalid IC result must be retested to obtain a valid result.
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V Substantial Equivalence Information:
A Predicate Device Name(s):
Aptima HCV Quant Dx assay
B Predicate 510(k) Number(s):
P160023
C Comparison with Predicate(s):
| Device & Predicate Device(s): | K233352 | P160023 |
| --- | --- | --- |
| Device Trade Name | Aptima HCV Quant Dx assay | Aptima HCV Quant Dx assay |
| General Device Characteristic Similarities | | |
| Intended Use | Same | The Aptima HCV Quant Dx assay is a real-time transcription-mediated amplification (TMA) test used for both detection and quantitation of hepatitis C virus (HCV) RNA in fresh and frozen human serum and plasma from HCV-infected individuals.
Plasma may be prepared in ethylenediaminetetraacetic acid (EDTA), anticoagulant citrate dextrose (ACD) solution, and plasma preparation tubes (PPT). Serum may be prepared in serum tubes and serum separator tubes (SST). Specimens are tested using the Panther system for automated specimen processing, amplification, detection, and quantitation.
Specimens containing HCV genotypes 1 to 6 are validated for detection and quantitation in the assay.
The Aptima HCV Quant Dx assay is indicated for use as an aid in the diagnosis of active HCV infection in the following populations: individuals with antibody evidence of HCV infection with evidence of liver |
K233352 - Page 7 of 11
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K233352 - Page 8 of 11
| | | disease, individuals suspected to be actively infected with HCV antibody evidence, and individuals at risk for HCV infection with antibodies to HCV. Detection of HCV RNA indicates that the virus is replicating and, therefore, is evidence of active infection. Detection of HCV RNA does not discriminate between acute and chronic states of infection.
The Aptima HCV Quant Dx assay is also indicated for use as an aid in the management of HCV infected patients undergoing HCV antiviral drug therapy. The assay can be used to measure HCV RNA levels periodically prior to, during, and after treatment to determine sustained virological response (SVR) or nonsustained virological response (NSVR). Assay performance characteristics have been established for individuals infected with HCV and treated with certain direct-acting antiviral agents (DAA) regimens. No information is available on the assay’s predictive value when other therapies are used. The results from the Aptima HCV Quant Dx assay must be interpreted within the context of all relevant clinical and laboratory findings.
The Aptima HCV Quant Dx assay is not approved for use as a screening test for the presence of HCV RNA in blood or blood products. |
| --- | --- | --- |
| Technology Principle of Operation | Same | Target Capture (TC), Transcription-Mediated Amplification (TMA) |
| Platform | Same | Automated Panther System |
| Assay Targets | Same | Hepatitis C RNA |
| Assay Results | Same | Qualitative & quantitative |
| Function | Same | Detection of RNA from Hepatitis C |
| General Device Characteristic Differences | | |
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| Reagents can be loaded onto the Panther system | 8 times | 5 times |
| --- | --- | --- |
| Results impacted by faulty or flickering LED in Panther instrument | Marked as invalid results | Read as normal, potentially producing incorrect results |
VI Standards/Guidance Documents Referenced:
No standards, special controls or guidance documents were referenced.
VII Performance Characteristics (if/when applicable):
NOTE: Performance Characteristics of the Aptima HCV Quant Assay other than the analytical studies described below have been described and established in P160023.
A Analytical Performance:
1. Precision/Reproducibility:
Refer to the original PMA submission P160023
2. Linearity:
Refer to the original PMA submission P160023
3. Analytical Specificity/Interference:
Refer to the original PMA submission P160023
4. Assay Reportable Range:
Not applicable.
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Estimated Background Process Control Limit Evaluation
The purpose of this study was to establish background process control limits necessary to detect faults such as flickering LED lamps or high background caused by contamination. LIS and fluorescent curve data were obtained from a customer field database. Curve files were processed to generate results processing output; estimated background data from the results processing output was matched with each test order in the LIS files. HCV Estimated Background distributions were analyzed by each channel. The estimated background limits did not increase the number of invalidated results.
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K233352 - Page 10 of 11
# Background Limits System Validation
The purpose of this study was to demonstrate that the Panther System can perform the assay per predefined acceptance criteria and that the assay performance with the revised software version is equivalent to the performance demonstrated with previous software versions. Performance was evaluated using HCV negative plasma and clinical virus spiked into plasma at 3x LLOQ (~30IU/mL). The results show that all 10 replicates for the negative sample were negative and all 10 replicates for the low positive sample were positive.
# On-Board Stability (OBS) and reagent Cycling:
The purpose of this study was to evaluate the Aptima HCV Quant Assay for an increase in the number of reagent on-board/off-board cycling to allow operators to load reagents onto the Panther System 8 times instead of 5 times. Performance was evaluated using negative clinical matrix and virus spiked into clinical plasma at the following concentrations: 30 IU/mL (3x LLoQ), 2E3 IU/mL, and 1E7 IU/mL. The results support on-board/off-board cycling claim of 8 times.
# Software Verification and Validation
Software validation testing of the functionality and feature set incorporated in the Panther and Panther Fusion System Software and associated assays was performed to ensure the software conforms to user needs and intended uses, and that the requirements implemented through software are consistently fulfilled. All verification testing passed meeting all the requirements.
6. Detection Limit:
Not applicable
7. Assay Cut-Off:
Refer to the original PMA submission P160023
8. Accuracy (Instrument):
Not applicable
9. Carry-Over:
Refer to the original PMA submission P160023
# B Comparison Studies:
1. Method Comparison with Predicate Device:
Refer to the original PMA submission P160023.
2. Matrix Comparison:
Refer to the original PMA submission P160023.
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C Clinical Studies:
1. Clinical Sensitivity:
Not applicable
2. Clinical Specificity:
Not applicable
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable
D Clinical Cut-Off:
Not applicable
E Expected Values/Reference Range:
Refer to the original PMA submission P160023.
F Other Supportive Instrument Performance Characteristics Data:
Not applicable.
VIII Proposed Labeling:
The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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