K252484 · Roche Molecular Systems, Inc. · MZP · Nov 3, 2025 · Microbiology
Device Facts
Record ID
K252484
Device Name
cobas HCV
Applicant
Roche Molecular Systems, Inc.
Product Code
MZP · Microbiology
Decision Date
Nov 3, 2025
Decision
SESE
Submission Type
Traditional
Regulation
21 CFR 866.3170
Device Class
Class 2
Indications for Use
cobas HCV is an in vitro nucleic acid amplification test for both the detection and quantitation of hepatitis C virus (HCV) RNA, in human EDTA plasma or serum, of HCV antibody positive or HCV-infected individuals. Specimens containing HCV genotypes 1 to 6 are validated for detection and quantitation in the assay. cobas HCV is intended for use as an aid in the diagnosis of HCV infection in the following populations: individuals with antibody evidence of HCV 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. cobas HCV is intended for use as an aid in the management of HCV-infected patients undergoing anti-viral therapy. The assay can be used to measure HCV RNA levels at baseline, during treatment, at the end of treatment, and at the end of follow up of treatment to determine sustained or non-sustained viral response. The results must be interpreted within the context of all relevant clinical and laboratory findings. cobas HCV has not been approved for use as a screening test for the presence of HCV in blood or blood products. Assay performance characteristics have been established for individuals treated with certain direct-acting antiviral agents (DAA) regimens. No information is available on the assay’s predictive value when other DAA combination therapies are used.
Device Story
cobas HCV is a quantitative nucleic acid amplification test for HCV RNA detection/quantitation in human EDTA plasma or serum. Performed on cobas 5800/6800/8800 Systems; process is fully automated, including nucleic acid extraction/purification using magnetic glass particles, reverse-transcription, and real-time PCR amplification. Input: patient sample + armored RNA quantitation standard (RNA-QS). Output: viral load titer (IU/mL). System uses dual detection probes for HCV and RNA-QS in separate channels; fluorescence signal measured during PCR cycles. Results interpreted by cobas software to aid diagnosis and monitor anti-viral therapy response. Used in clinical laboratory settings by trained personnel. Benefits include standardized, automated viral load monitoring to guide clinical decision-making for HCV-infected patients.
Clinical Evidence
Bench testing only. No new clinical trials were conducted; system equivalency was established via comparative performance studies. Studies included: Analytical Sensitivity (LoD) using dilution series (n=66 replicates/level); Linearity/LLoQ (n=36 replicates/level); Precision (n=72 replicates/level); and Method Comparison (n=155 positive specimens, n=30 negative specimens). Results demonstrated 100% agreement for negative samples and <0.5 log10 difference in viral load for positive samples between systems. All studies met predefined acceptance criteria.
Technological Characteristics
Real-time PCR assay; automated nucleic acid extraction using magnetic glass particles. Dual detection probes with fluorescent reporter dyes. Linear range: 15 IU/mL to 1.00E+08 IU/mL. Instrumentation: cobas 5800/6800/8800 Systems. Connectivity: automated barcode scanning and processing. Software: automated result interpretation via cobas system software.
Indications for Use
Indicated for HCV antibody-positive or infected individuals (genotypes 1-6) to detect and quantify HCV RNA in EDTA plasma or serum. Used as an aid in diagnosis for patients with antibody evidence and liver disease, suspected active infection, or risk factors. Used for management of patients on anti-viral therapy to measure viral load at baseline, during, and post-treatment. Not for blood/blood product screening.
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.
Predicate Devices
cobas HCV for use on the cobas 5800/6800/8800 Systems (K221007)
Related Devices
P150015 — COBAS HCV TEST · Roche Molecular Systems, Inc. · Oct 14, 2015
K221007 — cobas HCV · Roche Molecular Systems, Inc. · Nov 4, 2022
P060030 — COBAS AMPLIPREP/COBAS TAQMAN HCV TEST · Roche Molecular Systems, Inc. · Oct 30, 2008
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
K252484
B Applicant
Roche Molecular Systems, Inc.
C Proprietary and Established Names
cobas 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 of cobas HCV on the upgraded cobas 6800/8800 Systems 2.0.
B Measurand:
Hepatitis C virus (HCV) RNA
C Type of Test:
Nucleic acid amplification test
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):
cobas HCV is an in vitro nucleic acid amplification test for both the detection and quantitation of hepatitis C virus (HCV) RNA, in human EDTA plasma or serum, of HCV antibody positive or HCV-infected individuals. Specimens containing HCV genotypes 1 to 6 are validated for detection and quantitation in the assay.
cobas HCV is intended for use as an aid in the diagnosis of HCV infection in the following populations: individuals with antibody evidence of HCV 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.
cobas HCV is intended for use as an aid in the management of HCV-infected patients undergoing anti-viral therapy. The assay can be used to measure HCV RNA levels at baseline, during treatment, at the end of treatment, and at the end of follow up of treatment to determine sustained or non-sustained viral response. The results must be interpreted within the context of all relevant clinical and laboratory findings.
cobas HCV has not been approved for use as a screening test for the presence of HCV in blood or blood products.
Assay performance characteristics have been established for individuals treated with certain direct-acting antiviral agents (DAA) regimens. No information is available on the assay’s predictive value when other DAA combination therapies are used.
B Indication(s) for Use:
Same as Intended Use.
C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
D Special Instrument Requirements:
For use on the cobas 5800/6800/8800 Systems
IV Device/System Characteristics:
A Device Description:
cobas HCV assay is a quantitative test performed on the cobas 5800 System, cobas 6800 System or cobas 8800 System. The test detects and quantitates HCV RNA in EDTA plasma or serum of infected patients. Dual probes are used to detect and quantify but not discriminate genotypes 1–6. The viral load is quantified against a non-HCV armored RNA quantitation standard (RNA-QS),
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which is introduced into each specimen during sample preparation. The RNA-QS also functions as an internal control to assess substantial failures during the sample preparation and PCR amplification processes.
cobas HCV is based on fully automated sample preparation (nucleic acid extraction and purification) followed by reverse-transcription and PCR amplification.
## B Principle of Operation:
Nucleic acid from patient samples, external controls, and added armored RNA-QS molecules are simultaneously extracted by addition of proteinase and lysis reagent to the sample. The released nucleic acid is purified using magnetic glass particles.
Selective amplification of target nucleic acid from the sample is achieved by the use of target virus-specific primers which are selected from highly conserved regions of HCV. Selective amplification of RNA-QS is achieved by the use of sequence-specific primers which are selected to have no homology with the HCV genome. A thermostable DNA polymerase enzyme is used for both reverse-transcription and PCR amplification. The target and RNA-QS sequences are amplified simultaneously utilizing a universal PCR amplification profile. The cobas HCV master mix contains dual detection probes specific for the HCV target sequences and one for the RNA-QS. The probes are labeled with target-specific fluorescent reporter dyes allowing simultaneous detection of HCV target and RNA-QS in two different target channels.
During the PCR amplification step, hybridization of the probes to the specific single-stranded DNA template results in cleavage of the probe by the 5'-to-3' nuclease activity of the DNA polymerase resulting in separation of the reporter and quencher dyes and the generation of a fluorescent signal. With each PCR cycle, increasing amounts of cleaved probes are generated and the cumulative signal of the reporter dye increases concomitantly. Real-time detection and discrimination of PCR products is accomplished by measuring the fluorescence of the released reporter dyes for the viral targets and RNA-QS.
## Interpretation of Results.
Results are determined automatically by the cobas software and are shown in the following table:
Table 1. Individual Target Result Interpretation.
| Result Read-Out from cobas system | Analytical Interpretation | Clinical Interpretation |
| --- | --- | --- |
| Target Not Detected | HCV RNA not detected.
Report results as “HCV not detected.” | No current HCV infection
For HCV Diagnosis: No further testing indicated.*
For Viral Load Assessment: Routine clinical |
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| **< Titer Min** | HCV RNA detected but not quantified.
Calculated titer is below the Lower Limit of Quantitation (LLoQ) of the assay. Report results as “HCV detected, less than (Titer Min)”
Titer min = 15 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. |
| --- | --- | --- |
| 15 IU/mL≤ Titer < 25 IU/mL | HCV RNA detected and quantified.
Calculated titer is within the Linear Range of the assay – greater than or equal to 15 IU/mL and less than 25 IU/mL.
Report results as “(Titer) of HCV detected”. | 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≤ Titer ≤ Titer Max | HCV RNA detected and quantified
Calculated titer is within the Linear Range of the assay – greater than or equal to 25 IU/mL and less than or equal to Titer Max.
Report results as “(Titer) of HCV detected”. | Current 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. |
| > Titer Max | Calculated titer is above the Upper Limit of Quantitation (ULoQ) of the assay. Report results as “HCV detected, greater than (Titer Max).”
Titer max = 1.00E+08 IU/mL | Current 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. |
*Repeat HCV RNA testing if the person tested is suspected to have had HCV exposure within the past 6 months or has clinical evidence of HCV disease, or if there is concern regarding the handling or storage of the test specimen.
## C Instrument Description Information:
1. **Instrument Name:**
Cobas 5800/6800/8800 Systems
2. **Specimen Identification:**
cobas 5800/6800/8800 Systems support multiple types of barcodes. Loaded samples are automatically moved for barcode scanning and processing.
3. **Specimen Sampling and Handling:**
Specimen processing is fully automated on the cobas 5800/6800/8800 Systems.
4. **Calibration:**
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No instrument calibration is required by the user.
5. Quality Control:
Refer to cobas HCV assay labeling.
V Substantial Equivalence Information:
A Predicate Device Name(s):
cobas HCV
B Predicate 510(k) Number(s):
K221007
C Comparison with Predicate(s):
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| Device & Predicate Device(s): | Predicate Device | Candidate Device |
| --- | --- | --- |
| Device Trade Name | cobas HCV Quantitative nucleic acid test for use on the cobas 5800/6800/8800 Systems | same |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | cobas HCV is an in vitro nucleic acid amplification test for both the detection and quantitation of hepatitis C virus (HCV) RNA, in human EDTA plasma or serum, of HCV antibody positive or HCV-infected individuals. Specimens containing HCV genotypes 1 to 6 are validated for detection and quantitation in the assay.
cobas HCV is intended for use as an aid in the diagnosis of HCV infection in the following populations: individuals with antibody evidence of HCV 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.
cobas HCV is intended for use as an aid in the management of HCV-infected patients undergoing anti-viral therapy. The assay can be used to measure HCV RNA levels at baseline, during treatment, at the end of treatment, and at the end of follow up of treatment to determine sustained or non-sustained viral response. The results must be interpreted within the context of all relevant clinical and laboratory findings.
cobas HCV has not been approved for use as a screening test for the presence of HCV in blood or blood products.
Assay performance characteristics | same |
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| | have been established for individuals treated with certain direct-acting antiviral agents (DAA) regimens. No information is available on the assay’s predictive value when other DAA combination therapies are used. | |
| --- | --- | --- |
| Conditions for Use | For Prescription Use | same |
| Sample Types | Human EDTA Plasma, Serum | same |
| Analyte Targets | Hepatitis C RNA genotypes 1 to 6 | same |
| Sample Preparation Procedure | Automated | same |
| Amplification Technology | Real Time PCR | same |
| Detection Chemistry | Dual detection probes labeled with target-specific fluorescent reporter dyes allowing simultaneous detection of HCV target and RNA-QS in two different target channels. Real time detection and discrimination of PCR products is accomplished by measuring the fluorescence of the released reporter dyes. | same |
| Controls Used | RNA-QS functions as an internal control.
Three external controls: High Titer Positive, Low Titer Positive, Negative Control | same |
| Results Analysis | PCR cycle threshold analysis | same |
| General Device Characteristic Differences | | |
| Instrumentation | Cobas 5800 System | Cobas 6800/8800 Systems 2.0 |
VI Standards/Guidance Documents Referenced:
CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline- 2nd Edition. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.
CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline—Third Edition. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.
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CLSI EP06-Evaluation of Linearity of Quantitative Measurement Procedures – Second Edition. Clinical and Laboratory Standards Institute; 2020.
## VII Performance Characteristics:
## A Analytical Performance:
1. Precision/Reproducibility:
### A. Precision
The precision of cobas HCV was determined by analysis of serial dilutions of clinical HCV samples or of HCV positive artificial stock material (aRNA) in HCV-negative EDTA plasma. Seven dilution levels were tested in three replicates for each level in two runs across 12 days. Each sample was carried through the entire cobas HCV test procedure on 1 cobas 6800/8800 Systems 2.0 instruments and 1 cobas 6800/8800 Systems 1.4 instrument. The study was performed with three lots of cobas HCV test reagents.
The cobas HCV showed the following precision on the cobas 6800/8800 Systems 2.0 for three lots of reagents tested across a concentration range of 1.5E+01 IU/mL to 1.0E+08 IU/mL (Table 2):
Table 2. Within-Laboratory Precision of cobas HCV on the cobas 6800/8800 Systems 2.0
| Panel Member | mean observed log10 titer (IU/mL) | Lot | | Day | | Run | | Within-Run / Repeatability | | Total / Within-Laboratory | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Panel 1 | 7.97 | 0.01 | 0.07 | 0.00 | 0.00 | 0.01 | 0.17 | 0.02 | 0.22 | 0.02 | 0.29 |
| Panel 2 | 6.79 | 0.04 | 0.60 | 0.04 | 0.54 | 0.01 | 0.13 | 0.05 | 0.68 | 0.07 | 1.06 |
| Panel 3 | 5.92 | 0.03 | 0.53 | 0.03 | 0.48 | 0.00 | 0.00 | 0.05 | 0.84 | 0.07 | 1.11 |
| Panel 4 | 3.75 | 0.00 | 0.06 | 0.02 | 0.40 | 0.02 | 0.40 | 0.05 | 1.37 | 0.05 | 1.44 |
| Panel 5 | 1.79 | 0.00 | 0.00 | 0.00 | 0.00 | 0.06 | 3.13 | 0.11 | 6.30 | 0.13 | 7.04 |
| Panel 6 | 1.33 | 0.03 | 2.29 | 0.00 | 0.00 | 0.00 | 0.00 | 0.10 | 7.80 | 0.11 | 8.13 |
| Panel 7 | 1.36 | 0.11 | 8.23 | 0.00 | 0.00 | 0.00 | 0.00 | 0.18 | 13.34 | 0.21 | 15.68 |
SD: Standard Deviation; %CV: Percent Coefficient of Variation
## B. Reproducibility.
See P150015
2. Linearity:
Assay linearity was assessed using the predominant genotype (GT1) in plasma. The linearity panels were prepared as serial dilutions consisting of 16 concentration levels spanning the intended linear range and including medical decision points. The dilution series were
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prepared by diluting HCV armored RNA (aRNA) and an HCV positive clinical specimen in negative pooled EDTA-plasma. The Titer assignment of the study panels has been performed via Calibrator Bracketing Method. The dilution series covered a total of 36 replicates per concentration level in negative pooled EDTA plasma which were tested with 3 kit lots and tested on 3 cobas 6800/8800 Systems 2.0 over the course of 6 days.
With 500 µL processing volume, cobas HCV is linear for EDTA plasma from 15 IU/mL to 1.00E+08 IU/mL and shows an absolute deviation from the weighted least square linear regression of less than ± 0.24 log10. See Table 3 and Figure 1 below.
Table 3. cobas HCV Linearity on the cobas 6800/8800 Systems 2.0
| Sample Type | Panel Member | Assigned log10 Titer [IU/mL] | Relative Concentration | Mean Observed log10 Titer [IU/mL] | Expected log10 Titer [IU/mL] | Mean Predicted log10 Titer [IU/mL] | Deviation (observed - predicted) | Acceptance criterion | Acceptance criterion met? |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Armored RNA | PM1 | 8.18 | 1.00 | 8.32 | 8.32 | 8.23 | 0.09 | The absolute deviation for the linear regression shall be demonstrated to be equal to or less than ± 0.24 log10 for cobas 6800/8800 Systems 2.0. | N/A* |
| | PM2 | 7.88 | 0.96 | 8.00 | 8.01 | 7.93 | 0.07 | | YES |
| | PM3 | 6.88 | 0.84 | 7.00 | 7.00 | 6.92 | 0.08 | | |
| | PM4 | 5.88 | 0.72 | 6.01 | 5.98 | 5.92 | 0.10 | | |
| | PM5 | 5.48 | 0.67 | 5.59 | 5.58 | 5.52 | 0.07 | | |
| | PM7 | 3.88 | 0.47 | 3.89 | 3.95 | 3.90 | -0.01 | | |
| | PM9 | 3.48 | 0.43 | 3.48 | 3.54 | 3.50 | -0.03 | | |
| | PM11 | 2.88 | 0.35 | 2.89 | 2.93 | 2.90 | 0.00 | | |
| | PM13 | 1.88 | 0.23 | 1.93 | 1.91 | 1.89 | 0.04 | | |
| Clinical specimen | PM6 | 4.69 | 0.57 | 4.61 | 4.77 | 4.72 | -0.11 | | |
| | PM8 | 3.99 | 0.49 | 3.83 | 4.06 | 4.01 | -0.18 | | |
| | PM10 | 2.99 | 0.37 | 2.85 | 3.04 | 3.01 | -0.16 | | |
| | PM12 | 1.99 | 0.24 | 1.90 | 2.02 | 2.00 | -0.10 | | |
| | PM14 | 1.69 | 0.21 | 1.64 | 1.71 | 1.70 | -0.06 | | |
| | PM15 | 1.16 | 0.14 | 1.15 | 1.18 | 1.17 | -0.02 | | |
| | PM16 | 0.69 | 0.08 | 0.97 | 0.70 | 0.69 | 0.28 | | N/A* |
*Acceptance criterion is not applicable as the assigned titers for both PM1 and PM16 are not within the linear range (below ULoQ and above LLoQ).
Figure 1. Weighted Least Square Linear Regression (all 3 cobas 6800/8800 System 2.0)
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ObservedLog10Titer $= 0 + 0.9895621^{*}$ expected Log10 Titer
3. Analytical Specificity/Interference:
See P150015
4. Assay Reportable Range:
The results of the linearity study and calculation of the Lower and Upper Limits of Quantitation confirm the assay reportable range is consistent across analyzer platforms: 15 IU/mL - 1.00E+08 IU/mL.
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
See P150015
6. Detection Limit:
The Limit of Detection (LoD) was assessed with a sample panel prepared by diluting an HCV secondary standard in HCV negative pooled EDTA plasma. The dilution series was prepared with 5 HCV concentration levels including 2 levels below the expected LoD, 1 level near the expected LoD, and 2 levels above the expected LoD. The panel was tested with 3 kit lots, on 5 days, on 3 cobas 6800/8800 Systems 2.0 and 1 cobas 6800/8800 System 1.4 over multiple runs, with multiple operators and with multiple replicates per run. A summary of the LoD results is provided in the table below.
Table 4. Results Summary cobas HCV LoD HCV on the cobas 6800/8800 System 1.4 and the cobas 6800/8800 System 2.0
| Platform | LoD by PROBIT analysis (95% Hit Rate) Lower & Upper 95% CI | Target: HCV |
| --- | --- | --- |
| cobas 6800/8800 Systems 2.0 | PROBIT analysis (95% Hit Rate) Lower & Upper 95% CI | 14.01 IU/mL (95% CI: 11.33-18.91) |
| | LoD by Hit Rate | 15 IU/mL |
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| | log10 PROBIT 95% | 1.15 |
| --- | --- | --- |
| cobas 6800/8800
Systems 1.4 | PROBIT analysis (95% Hit Rate) Lower & Upper 95% CI | 11.86 IU/mL
(95% CI: 9.61-16.11) |
| | LoD by Hit Rate | 15 IU/mL |
| | log10 PROBIT 95% | 1.07 |
| log10 PROBIT 95% Delta
(cobas 6800/8800 Systems 2.0– cobas 6800/8800 Systems 1.4) | | 0.07 |
| Acceptance Criterion met/not met
(± 0.2 Log10) | | Met |
7. **Assay Cut-Off:**
See P150015
8. **Accuracy (Instrument):**
N/A
9. **Carry-Over:**
See P150015
## B Comparison Studies:
1. **Method Comparison with Predicate Device:**
A method comparison study was conducted using 155 archived HCV positive plasma specimens and 30 HCV negative individual plasma specimens. Some of the individual positive specimens were diluted to achieve the desired number of samples at specified concentrations: ~50 HCV specimens between 1.5 E+01 to 3E+03 IU/mL, ~50 specimens between 3E+03 to 5E+05 IU/mL and ~50 specimens between 5E+05 to 1E+08 IU/mL. Each specimen was tested on three cobas 6800/8800 Systems 2.0 and on one cobas 6800/8800 System 1.4 at one external site using three reagent lots.
**Results:**
For the 30 samples with target not detected (TND) results by cobas 6800/8800 Systems 1.4, the NPA was 100% (30/30).
All of the positive samples were within the linear range of 1.5E+1 IU/mL to 1E+8 IU/mL by cobas 6800/8800 Systems 1.4 (155/155 =100%) and by cobas 6800/8800 Systems 2.0 (465/465=100%). Among the three categories (low, medium, and high viral loads) within the linear range, the test results between the two Systems were highly concordant.
Table 5 summarizes the parameter estimates (slope and intercept) of Deming regression between cobas 6800/8800 Systems 2.0 and cobas 6800/8800 Systems 1.4 by instrument.
**Table 5. Overall and by-instrument parameter estimates from Deming regression analysis.**
| Instrument | Number of Pairs within Linear Range | Parameter | Parameter Estimate | 95% CI | r² |
| --- | --- | --- | --- | --- | --- |
| Overall | 459 | Intercept | 0.13 | 0.09 – 0.17 | 0.99 |
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| | | Slope | 0.98 | 0.97 – 0.99 | |
| --- | --- | --- | --- | --- | --- |
| 1 | 153 | Intercept | 0.19 | 0.14 – 0.24 | 0.99 |
| | | Slope | 0.97 | 0.96 – 0.98 | |
| 2 | 153 | Intercept | 0.10 | 0.05 – 0.16 | 0.99 |
| | | Slope | 0.98 | 0.97 – 0.99 | |
| 3 | 153 | Intercept | 0.10 | 0.02 – 0.17 | 0.99 |
| | | Slope | 0.99 | 0.97 – 1.00 | |
Figure 2. Deming regression result of the averaged log10-transformed viral load concentration across 3 cobas 6800/8800 Systems 2.0 versus log10-transformed viral load concentration from the cobas 6800/8800 Systems 1.4.
Using Deming regression analysis, an estimate of the systematic bias between the log10-transformed viral load concentration of the two Systems (cobas 6800/8800 Systems 2.0 and cobas 6800/8800 Systems 1.4) was calculated at medical decision levels for each site. Jackknife method was used to estimate the $95\%$ CI of systematic bias (Table 6).
Table 6. Systematic bias at medical decision point by instrument, based on Deming regression.
| Instrument | Medical Decision Point (IU/mL) | Number of Pairs within Linear Range | Medical Decision Point in log10 (IU/mL) | Predicted Value at Medical Decision Point in log10 (IU/mL) | Bias in log10 (IU/mL) |
| --- | --- | --- | --- | --- | --- |
| 1 | 25 | 150 | 1.398 | 1.542 | 0.1443 |
| | 800,000 | 150 | 5.903 | 5.903 | 0.0 |
| | 6,000,000 | 150 | 6.778 | 6.750 | -0.028 |
| | 25 | 150 | 1.398 | 1.472 | 0.074 |
| | 800,000 | 150 | 5.903 | 5.887 | -0.016 |
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| 2 | 6,000,000 | 150 | 6.778 | 6.744 | -0.033 |
| --- | --- | --- | --- | --- | --- |
| 3 | 25 | 150 | 1.398 | 1.476 | 0.078 |
| | 800,000 | 150 | 5.903 | 5.922 | 0.019 |
| | 6,000,000 | 150 | 6.778 | 6.786 | 0.008 |
| combined | 25 | 150 | 1.398 | 1.496 | 0.098 |
| | 800,000 | 150 | 5.903 | 5.902 | -0.001 |
| | 6,000,000 | 150 | 6.778 | 6.758 | -0.020 |
A Bland-Altman plot between the results of the two Systems (cobas 6800/8800 Systems 2.0 and cobas 6800/8800 Systems 1.4) with allowable total difference (ATD) zone were created for each site and for all sites combined (Table 7). Over the entire range, 100% of the samples fell within the ATD zone and the lower bound of the one-sided 95% CI was 100%.
Table 7. Percentage of samples within the ATD zone and ±0.5 log10-range by all instruments combined.
| Instrument | Viral Load Range Category | Viral Load Range (IU/mL) | Percentage of Samples within ATD Zone (95% One-Sided CI) | Percentage of Samples with difference within ±0.5 log10 (95% One-Sided CI) |
| --- | --- | --- | --- | --- |
| Overall | Low | 1.50E+01 - 3.00E+03 | 100% (153/153) (98.26%) | 100% (153/153) (98.26%) |
| | Medium | 3.00E+03 - 5.00E+05 | 100% (203/203) (98.68%) | 100% (203/203) (98.68%) |
| | High | 5.00E+05 - 1.00E+08 | 100% (103/103) (97.44%) | 100% (103/103) (97.44%) |
| | Overall | | 100% (459/459) (99.41%) | 100% (459/459) (99.41%) |
| CI = Confidence Interval | | | | |
2. Matrix Comparison:
See P150015
C Clinical Studies:
1. Clinical Sensitivity:
See P150015
2. Clinical Specificity:
See P150015
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
N/A
D Clinical Cut-Off:
See P150015
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K252484 - Page 14 of 14
E Expected Values/Reference Range:
See P150015
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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