# SUMMARY OF SAFETY AND EFFECTIVENESS {#summary-of-safety-and-effectiveness .unnumbered}

## GENERAL INFORMATION

###  {#section .unnumbered}

### Device Generic Name: In vitro nucleic acid amplification assay for the detection of hepatitis C virus (HCV) RNA in human plasma or serum. {#device-generic-name-in-vitro-nucleic-acid-amplification-assay-for-the-detection-of-hepatitis-c-virus-hcv-rna-in-human-plasma-or-serum. .unnumbered}

###  Device Trade Name: VERSANT  HCV RNA Qualitative Assay {#device-trade-name-versant-hcv-rna-qualitative-assay .unnumbered}

Applicant's Name and Address: Gen-Probe Incorporated

> 10210 Genetic Center Drive
>
> San Diego, CA 92121

###  Premarket Approval Application (PMA) Number: P020011 {#premarket-approval-application-pma-number-p020011 .unnumbered}

Date of Panel Recommendation: None

###  {#section-1 .unnumbered}

### Date of Notice of Approval to Applicant: November 7, 2002 {#date-of-notice-of-approval-to-applicant-november-7-2002 .unnumbered}

## INDICATIONS FOR USE

> The VERSANT HCV RNA Qualitative Assay is an *in vitro* nucleic acid
> amplification assay for the detection of hepatitis C virus (HCV) RNA
> in human plasma (EDTA, sodium heparin, sodium citrate, and ACD) or
> serum. The VERSANT HCV RNA Qualitative Assay is indicated for use with
> fresh or frozen specimens from the following populations: individuals
> with antibody evidence of HCV infection with evidence of liver
> disease, and individuals suspected to be actively infected with HCV
> with antibody evidence, and individuals at risk for HCV infection with
> antibodies to HCV. Detection of HCV RNA is evidence of active HCV
> infection.
>
> Detection of HCV RNA does not discriminate between an acute and
> chronic state of infection or indicate the presence of liver disease.
> A negative result does not exclude active HCV replication. It is not
> known if performance is affected by the state of HCV infection (acute
> or chronic) or by the presence or absence of liver disease.
> Performance has not been demonstrated for monitoring HCV infected
> patients.
>
> **WARNING: This assay has not been FDA-approved for the screening of
> blood or plasma donors.**

##  {#section-2 .unnumbered}

## III. DEVICE DESCRIPTION {#iii.-device-description .unnumbered}

###  {#section-3 .unnumbered}

The VERSANT HCV RNA Qualitative Assay is a target amplification-based
nucleic acid probe test that detects HCV RNA in human plasma and serum.
The VERSANT HCV RNA Qualitative Assay utilizes Transcription-Mediated
Amplification (TMA) to amplify conserved regions within the 5'
untranslated region (5\'-UTR) of the HCV genome. TMA utilizes Moloney
Murine Leukemia Virus (MMLV) reverse transcriptase (RT) and T7 RNA
polymerase to generate multiple RNA copies from the viral nucleic acid
template. Assay performance is monitored by means of an internal nucleic
acid control that is added to each specimen with the Target Capture
Reagent.

The VERSANT HCV RNA Qualitative Assay has three main steps, all of which
are performed within a single tube: sample preparation, target
amplification, and amplicon detection.

The VERSANT HCV RNA Qualitative Assay consists of the following kits:

> The HCV RNA Qualitative Assay Master Kit
>
> The Auto Detect Reagent Kit
>
> The HCV RNA Qualitative Assay Control Kit

Each kit contains labeled reagents assembled according to storage
temperature requirements (frozen \[-15° to -35°C\]; refrigerated \[2° to
8°C\] and controlled room temperature \[15° to 30°C\]).

## IV. CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS {#iv.-contraindications-warnings-and-precautions .unnumbered}

## There are no known contraindications for the VERSANT HCV RNA Qualitative Assay. {#there-are-no-known-contraindications-for-the-versant-hcv-rna-qualitative-assay. .unnumbered}

Refer to the Package Insert for a listing of warnings and precautions.

##  {#section-4 .unnumbered}

## V. ALTERNATE PRACTICES AND PROCEDURES {#v.-alternate-practices-and-procedures .unnumbered}

Currently, the diagnosis of HCV infection is largely established using
serologic screening with EIA for anti-viral antibodies followed by
supplemental testing with RIBA. The technology for detection of anti-HCV
has progressed to third generation EIA and RIBA assays. Detection of HCV
antibody is primarily limited due to the elapsed time from acute
infection to seroconversion, which may take from three to six months.
Furthermore, in patients who are immunosuppressed or immunocompromised,
such as by infection with human immunodeficiency virus (HIV) or chronic
renal failure (i.e., dialysis patients), evidence of anti-HCV
seroconversion may never occur. Additionally, anti-HCV serology tests
cannot distinguish between active and inactive viral replication.

Recently, nucleic acid amplification tests (NAATs) have been developed,
which can detect HCV RNA in serum or plasma within one to two weeks
after exposure to the virus and weeks before the onset of ALT elevations
or the appearance of anti-HCV.

VI. **MARKETING HISTORY**

The VERSANT HCV RNA Qualitative Assay received approval outside the U.S.
to be marketed in France, Japan, and Canada.

The VERSANT HCV RNA Qualitative Assay has not been withdrawn from
marketing for any reason related to the safety or effectiveness of the
product.

##  {#section-5 .unnumbered}

##  POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

The only adverse effect of the Versant HCV RNA, as with all *in vitro*
diagnostic assays, is the possibility of misdiagnosis due to a an
erroneous test result, which is likely due to a false positive or a
false negative test result.

In the case of a false positive result, patients may be subjected to
unnecessary medical interventions or faced with undesirable social
implications. A false negative result may delay needed intervention to
mediate pain and suffering and improve health or allow for the continued
transmission of an infectious disease.

A false positive VERSANT HCV RNA Qualitative Assay test result may
initiate certain medical interventions associated with the diagnosis and
treatment of HCV infection. A presumptive misdiagnosis of HCV infection
may occur if the false positive result is coincident with an ALT value
that was elevated due to other reasons. As a result, the patient would
be subject to undue psychological stress and a liver biopsy with its
potential for side effects. False positive results may be caused by the
presence of cross-reacting species in the specimen, procedural errors,
carryover contamination, specimen misidentification, or transcription
errors.

A false negative VERSANT HCV RNA Qualitative Assay test result may delay
needed diagnostic procedures to identify those at risk or suspected of
having HCV infection. Due to the parenteral means of disease
transmission, failure to identify infected individuals may increase the
likelihood of new cases of HCV infection. False negative results may be
caused by specimen inhibition, interfering substances, procedural
deviations, use of the test by unqualified personnel, or transcription
errors.

## SUMMARY OF NONCLINICAL STUDIES

Nonclinical studies were conducted to establish the analytical
performance and potential limitations of the VERSANT HCV RNA Qualitative
Assay. The effects of non-HCV factors on assay performance
(non-specificity studies) were also included in the studies. These
nonclinical laboratory studies were performed by the Research and
Development Department (R&D) at Gen-Probe Incorporated and by the
Nucleic Acid Assay Development Laboratory at Bayer Diagnostics, Bayer
Corporation.

The performance characteristics determined through the conduct of the
nonclinical testing are summarized in the package insert for the VERSANT
HCV RNA Qualitative Assay. Brief summaries of the results from the
nonclinical studies are also provided in the following sections.

## Specificity {#specificity .unnumbered}

The specificity of the VERSANT HCV RNA Qualitative Assay was determined
using 1,000 serum and 1,504 EDTA plasma specimens from anti-HCV negative
volunteer blood donors. The specimens were negative for antibodies to
HCV using FDA approved methods. Of the total samples tested, 2,495/2,504
was nonreactive in the VERSANT HCV RNA Qualitative Assay, yielding a
specificity of 99.6%.

##  {#section-6 .unnumbered}

## Analytical Sensitivity {#analytical-sensitivity .unnumbered}

### 1. Limit of Detection (WHO International Standard) {#limit-of-detection-who-international-standard .unnumbered}

The Limit of Detection (LOD) for the VERSANT HCV RNA Qualitative Assay
was determined by testing serial dilutions of the WHO International
Standard for HCV genotype 1 RNA (NIBSC code 96/790). The tables in the
package insert present the percent detection of each panel member. Each
panel member was tested in replicates ranging from 60 to 240.

Serial dilutions of the WHO International Standard for HCV genotype 1
RNA were detected ≥95% of the time as low as 7.5 IU/mL. Linear
regression analysis determined 5.3 IU/mL (95% probability) as the limit
of detection for the VERSANT HCV RNA Qualitative Assay.

### 2. Detection of HCV Genotypes Using RNA Transcripts {#detection-of-hcv-genotypes-using-rna-transcripts .unnumbered}

Transcripts of HCV genotypes 1, 2a, 2b, 3a, 4a, 5a, and 6a made from the
5'-untranslated region of the HCV genome were tested using the VERSANT
HCV RNA Qualitative Assay. All transcripts were quantitated using
phosphate analysis and confirmed using hyperchromicity and OD~260~. The
copies/mL were converted to IU/mL using an in-house conversion factor:
5.2 copies/mL = 1 IU/mL.

Dilutions of each transcript were tested at 9.6 IU/mL (50 copies/mL) for
genotypes 1, 2a, 3a, 4a, 5a, and 6a. Genotype 2b was diluted to 14.4
IU/mL (75 copies/mL). Each transcript was tested in replicates ranging
from 360 to 720. The results are presented in the package insert.

With the exception of genotype 2b, all genotype transcripts were
detected ≥95% of the time at 9.6 IU/mL (50 copies/mL). Genotype 2b was
detected ≥95% of the time at 14.4 IU/mL (75 copies/mL).

#### 3. Detection of HCV Genotypes Using Clinical Specimens {#detection-of-hcv-genotypes-using-clinical-specimens .unnumbered}

Clinical specimens representing HCV genotypes 1 to 6 at different
concentrations were used to determine the percent detection of the
VERSANT HCV RNA Qualitative Assay. The specimens were quantitated using
the VERSANT HCV RNA 3.0 Assay (bDNA). The genotypes of the specimens
were provided by the specimen vendor and confirmed using the VERSANT HCV
Genotype Assay (LiPA) and sequencing. The results are presented in the
package insert. The overall percent detected across all HCV genotypes
tested was ≥95% at 9.6 IU/mL (50 copies/mL).

In a supplemental study, 61 clinical specimens representing genotypes 1
to 6 were tested at 1,00, 300 and 100 c/mL; no testing was performed at
50 c/mL. With the exception of specimens representing HCV genotype 2,
all specimens were detected at all levels. All clinical specimens
containing HCV genotypes 1 to 6 showed reactivity in the VERSANT HCV RNA
Assay. These included 8 specimens in the transcript testing, 6 in the
clinical specimen testing, and 61 in the supplemental testing.

### Analytical Specificity {#analytical-specificity .unnumbered}

####  {#section-7 .unnumbered}

#### 1. Cross Contamination Frequency {#cross-contamination-frequency .unnumbered}

The potential cross-contamination frequency was determined by testing
replicates of a high titer HCV genotype 1 positive specimen and
replicates of an HCV negative specimen. HCV positive samples (1 x 10^6^
copies/mL) were alternated with HCV negative samples using a
"checkerboard" pattern. Forty-five (45) replicates each of HCV negative
and HCV positive samples were tested in each of five runs, for a total
of 225 replicates of the HCV positive samples and 225 replicates of the
HCV negative samples. No false results were obtained; two negative
samples were invalid. Combined results across all runs yielded a
cross-contamination frequency of 0% (0/223).

#### 2. Microorganisms and Viruses {#microorganisms-and-viruses .unnumbered}

The potential cross-reaction and interference of other microorganisms
and viruses was evaluated by adding selected microorganisms and viruses
to HCV negative specimens and specimens spiked with HCV genotype 1 at
9.6 IU/mL (50 copies/mL); skin flora microorganisms that may contaminate
a blood sample or microorganisms and viruses that can co-infect
individuals with HCV infection were tested.

The microorganisms and viruses were pooled and tested at final
concentrations of 5 x 10^4^ CFU/mL or 5 x 10^4^ copies/mL, respectively.
Pool 1 contained *E. coli, P. aeruginosa, K. pneumoniae, H. influenzae,*
and cytomegalovirus (CMV) (Towne). Pool 2 contained *E. cloacae, P.
fluorescens, S. aureus, S. marcescens,* and *S. pneumoniae.* Pool 3
contained *S. epidermidis,* Streptococcus group B, *C. albicans,*
hepatitis B virus (HBV), and HIV-1 B. Pool 4 contained HIV-1 A, HIV-1 C,
and HIV-1 D. Pool 5 contained HIV-1 E, HIV-1 F, HIV-1 O and *P. acnes*.
Hepatitis G virus (HGV) also was tested both in the presence and absence
of spiked HCV 1a at 9.6 IU/mL (50 copies/mL) using five HGV-positive
specimens. HGV titers were not known due to the lack of an HGV
quantitative assay. For all microorganisms and viruses tested, no
cross-reactions or interference were observed in the VERSANT HCV RNA
Qualitative Assay.

###  {#section-8 .unnumbered}

### Potentially Interfering Substances {#potentially-interfering-substances .unnumbered}

#### 1. Endogenous Substances {#endogenous-substances .unnumbered}

Potentially interfering endogenous substances were tested by adding
these substances to HCV negative specimens and specimens spiked with HCV
genotype 1 at 9.6 IU/mL (50 copies/mL). The concentrations of
potentially interfering endogenous substances were tested according to
NCCLS Document EP7-P.

The following endogenous substances were tested: 500 mg/dL hemoglobin,
60 mg/dL bilirubin (conjugated), 60 mg/dL bilirubin (unconjugated),
3,000 mg/dL triglycerides, and 8 g/dL protein. None of the endogenous
substances tested interfered with the sensitivity and specificity of the
VERSANT HCV RNA Qualitative Assay.

#### 2. Therapeutic Drugs {#therapeutic-drugs .unnumbered}

The potential interference of commonly prescribed drugs to treat HCV or
other viral diseases was tested by adding these substances to HCV
negative specimens and specimens spiked with HCV genotype 1 at 9.6 IU/mL
(50 copies/mL). The drugs were pooled and tested at final concentrations
five times the reported peak serum or plasma concentrations in the
therapeutic range. Pool 1 contained Intron A, Ribavirin, and
Azathioprine. Pool 2 contained Cyclosporine, Aldactone, and Prednisone.
Pool 3 contained Roferon A, Tacrolimus, and Amantadine HCl. Pool 4
contained Fluoxetine HCl, Peginterferon Alfa-2b, and Azidothymidine.
Pool 5 contained Ganciclovir and Dideoxycytidine, and Pool 6 contained
Didanosine and Didehydrodeoxythymidine. None of the drugs tested
interfered with the sensitivity and specificity of the Versant HCV RNA
Qualitative Assay.

#### 3. Other Potentially Interfering Substances {#other-potentially-interfering-substances .unnumbered}

The effect of other potentially interfering substances was determined by
testing HCV negative specimens and specimens spiked with HCV genotype 1
at 9.6 IU/mL (50 copies/mL). The disease categories tested were: myeloma
IgG (n=12) positive specimens, anti-nuclear antibody positive specimens
(n=10), anti-doublestranded DNA positive specimens (n=6), rheumatoid
factor positive specimens (n=19), and specimens from subjects with
systemic lupus erythematous (n=10).

With the exception of a subset of the myeloma specimens, none of the
tested samples from subjects with HCV-like disease states interfered
with the performance of the VERSANT HCV RNA Qualitative Assay. Refer to
the Limitations section of the package insert for information on myeloma
specimens.

#### 4. Specimen Collection (Commonly Used Anticoagulants) {#specimen-collection-commonly-used-anticoagulants .unnumbered}

HCV-negative specimens and specimens spiked with HCV genotype 1 at 9.6
IU/mL (50 copies/mL) were collected in serum separator tubes (SST PLUS,
plastic), K~2~ EDTA (PLUS, plastic), K~2~ EDTA (PPT), sodium citrate
(glass, 4%), ACD-solution A (glass) and sodium heparin (PLUS, plastic 60
USP units) tubes. None of the anticoagulants tested affected the
sensitivity and specificity of the VERSANT HCV RNA Qualitative Assay.

## SUMMARY OF CLINICAL STUDIES

Performance characteristics for the VERSANT HCV RNA Qualitative Assay
were established in a multi-center study at four geographically diverse
clinical sites. In the study, serum or plasma specimens from 1,511
subjects enrolled in hepatology clinics, intravenous drug abuse clinics,
transfusion centers and AIDS clinics were evaluated. The study
population included 938 (62.1%) subjects with a medical history of liver
disease or positive anti-HCV serology and 741 (49.0%) subjects diagnosed
with chronic HCV hepatitis. A history of one or more risk factors was
reported by 1,175 (77.8%) subjects. Symptoms associated with HCV
infection were reported by 741 (49.0%) subjects and 112 (7.4%) subjects
were infected with HIV or another hepatitis virus. No patients were on
anti-viral therapy at the time of enrollment into the study.

Of the 1,511 total subjects, 544 (36.0%) were female and 967 (64.0%)
were male. Subject age ranged from 17 years to 89 years with a mean of
47 years. Ethnicity representation included: White, Non-Hispanic, 689
(45.6%); Black, Non-Hispanic, 588 (38.9%); White, Hispanic,\
149 (9.9%); Asian/Pacific Islander, 23 (1.5%); Black, Hispanic, 19
(1.3%); Native American, Alaskan, 8 (0.5%); and unknown or other, 35
(2.3%).

## CLINICAL STUDY RESULTS {#clinical-study-results .unnumbered}

A total of 5,542 EIA, RIBA, PCR and VERSANT HCV RNA Qualitative Assay
results were used in the clinical data analysis. Performance
characteristics were based on calculations of Positive and Negative
Percent Agreement and 95% Confidence Intervals of VERSANT HCV RNA
Qualitative Assay results compared to anti-HCV serology results and to
PCR results in three different populations: subjects with or without
anti-HCV, subjects with anti-HCV with or without biochemical (i.e.,
elevated ALT) or histological evidence of liver disease, and subjects at
risk for HCV with or without anti-HCV. Liver histopathology was
characterized by cirrhosis, fibrosis, hepatocelluar carcinoma, or other
histopathological diagnosis. Subjects were classified as "at risk for
HCV" if they were exposed to needle-stick accidents or another
occupational exposure, blood or blood product transfusion, past or
current injection-drug use or use of shared drug tools, multiple sex
partners, sex with an HCV-positive partner, men having sex with men,
dialysis, or a history of a sexually transmitted disease (STD).

For assay comparisons made within each population, performance of the
VERSANT HCV RNA Qualitative Assay was similar across the four study
sites and for each specimen type. Summary data are provided in Tables
IX-1 and IX-.2 for each population and overall. Serum and plasma data
are shown combined.

## Comparison with Anti-HCV Serology {#comparison-with-anti-hcv-serology .unnumbered}

Performance of the VERSANT HCV RNA Qualitative Assay compared to
anti-HCV serology was similar for each population and overall as shown
in Table IX-1. Of the 1,511 VERSANT HCV RNA Qualitative Assay and
anti-HCV results available in subjects with or without evidence of HCV,
ten (10) anti-HCV serology results were indeterminate. Of the remaining
1,501 VERSANT HCV RNA Qualitative Assay and conclusive anti-HCV results
available in this population, 93.6% were in agreement between the two
assays. The VERSANT HCV RNA Qualitative Assay detected HCV RNA in 930 of
1,014 (91.7% Positive Agreement) anti-HCV serology positive specimens,
but not in 475 of 486 (97.7% Negative Agreement) anti-HCV serology
negative specimens. Sixteen (16) results were RIBA indeterminate or
negative, however, five (5) of the 16 were PCR positive. Therefore,
these five (5) subjects were infected. The VERSANT HCV RNA Qualitative
Assay agreed with all 5 of these results (100%).

Of the 522 specimens collected from subjects with anti-HCV and
biochemical or histological evidence of liver disease, the VERSANT HCV
RNA Qualitative Assay detected HCV RNA in 486 (93.1%) specimens. HCV RNA
was detected in: (a) 368 (98.7%) of 373 specimens from subjects with
elevated ALT and liver histopathology, (b) 92 (74.8%) of 123 specimens
from subjects with normal ALT and liver histopathology, and (c) 26
(100%) of 26 specimens from subjects with elevated ALT and no liver
histopathology. Of the 129 specimens collected from subjects without
anti-HCV with evidence liver disease, the VERSANT HCV RNA Qualitative
Assay did not detect HCV RNA in 127 (98.4%) specimens. Six (6) results
were RIBA indeterminate or negative; however, three (3) of the six (6)
were PCR positive. Therefore, these three (3) subjects were infected.
The VERSANT HCV RNA Qualitative Assay agreed with all three (3) of these
results (100%).

Of the 1,175 subjects at risk for HCV, the VERSANT HCV RNA Qualitative
Assay detected HCV RNA in 765 of 831 (92.1%) anti-HCV serology positive
specimens, but not in 328 of 336 (97.6%) anti-HCV serology negative
specimens. Nine (9) results were RIBA indeterminate or negative;
however, PCR was positive for four (4) of the nine (9) subjects,
indicating that they were infected. The VERSANT HCV RNA Qualitative
Assay agreed with all four (4) of these results (100%).

<table>
<colgroup>
<col style="width: 17%" />
<col style="width: 6%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 10%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="10"><strong>Table IX-1. Agreement of the VERSANT HCV RNA
Qualitative Assay and Anti-HCV Serology for Each Study
Population</strong></td>
</tr>
<tr class="even">
<td></td>
<td><strong>N</strong></td>
<td><p><strong>VERSANT+</strong></p>
<p><strong>Serology+</strong></p></td>
<td><p><strong>VERSANT+</strong></p>
<p><strong>Serology-</strong></p></td>
<td><p><strong>VERSANT-</strong></p>
<p><strong>Serology+</strong></p></td>
<td><p><strong>VERSANT-</strong></p>
<p><strong>Serology-</strong></p></td>
<td><strong>% Negative Agreement</strong></td>
<td><p><strong>95%</strong></p>
<p><strong>C.I.</strong></p></td>
<td><strong>% Positive Agreement</strong></td>
<td><p><strong>95%</strong></p>
<p><strong>C.I.</strong></p></td>
</tr>
<tr class="odd">
<td><strong>Total</strong></td>
<td>1511</td>
<td>935</td>
<td>11</td>
<td>84</td>
<td>481</td>
<td>97.8</td>
<td>96.0-98.9</td>
<td>91.8</td>
<td>89.9-93.4</td>
</tr>
<tr class="even">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td><strong>Anti-HCV Serology</strong></td>
<td>1511</td>
<td>935</td>
<td>11</td>
<td>84</td>
<td>481</td>
<td>97.8</td>
<td>96.0-98.9</td>
<td>91.8</td>
<td>89.9-93.4</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Pos</td>
<td>1014</td>
<td>930</td>
<td>0</td>
<td>84</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>91.7</td>
<td>89.8-93.3</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Neg</td>
<td>6</td>
<td>1<sup>1</sup></td>
<td>0</td>
<td>0</td>
<td>5</td>
<td>100</td>
<td>47.8- 100</td>
<td>100</td>
<td>2.5- 100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Ind</td>
<td>10</td>
<td>4<sup>1</sup></td>
<td>0</td>
<td>0</td>
<td>6<sup>3</sup></td>
<td>100</td>
<td>54.1- 100</td>
<td>100</td>
<td>39.8- 100</td>
</tr>
<tr class="odd">
<td>EIA NR<sup>2</sup></td>
<td>481</td>
<td>0</td>
<td>11</td>
<td>0</td>
<td>470</td>
<td>97.7</td>
<td>95.9-98.9</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td colspan="10"><strong>Anti-HCV Serology, ALT, Liver Histological
Findings</strong></td>
</tr>
<tr class="even">
<td><strong>Total</strong></td>
<td>658</td>
<td>490</td>
<td>2</td>
<td>37</td>
<td>129</td>
<td>98.5</td>
<td>94.6-99.8</td>
<td>93.0</td>
<td>90.5-95.0</td>
</tr>
<tr class="odd">
<td><strong>Elevated ALT and Liver Histopathology</strong></td>
<td>425</td>
<td>371</td>
<td>0</td>
<td>5</td>
<td>49</td>
<td>100</td>
<td>92.7- 100</td>
<td>98.7</td>
<td>96.9-99.6</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Pos</td>
<td>373</td>
<td>368</td>
<td>0</td>
<td>5</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>98.7</td>
<td>96.9-99.6</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Neg</td>
<td>3</td>
<td>1<sup>1</sup></td>
<td>0</td>
<td>0</td>
<td>2</td>
<td>100</td>
<td>15.8- 100</td>
<td>100</td>
<td>2.5- 100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Ind</td>
<td>3</td>
<td>2<sup>1</sup></td>
<td>0</td>
<td>0</td>
<td>1<sup>3</sup></td>
<td>100</td>
<td>2.5- 100</td>
<td>100</td>
<td>15.8- 100</td>
</tr>
<tr class="odd">
<td>EIA NR<sup>2</sup></td>
<td>46</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>46</td>
<td>100</td>
<td>92.3-100</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td><strong>Normal ALT and Liver Histopathology</strong></td>
<td>205</td>
<td>92</td>
<td>2</td>
<td>31</td>
<td>80</td>
<td>97.6</td>
<td>91.5-99.7</td>
<td>74.8</td>
<td>66.2-82.2</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Pos</td>
<td>123</td>
<td>92</td>
<td>0</td>
<td>31</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>74.8</td>
<td>66.2-82.2</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Neg</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>100</td>
<td>2.5-100</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Ind</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>1<sup>3</sup></td>
<td>100</td>
<td>2.5- 100</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td>EIA NR<sup>2</sup></td>
<td>80</td>
<td>0</td>
<td>2</td>
<td>0</td>
<td>78</td>
<td>97.5</td>
<td>91.3-99.7</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td><strong>Elevated ALT and No Liver Histopathology</strong></td>
<td>26</td>
<td>26</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>100</td>
<td>86.8-100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Pos</td>
<td>26</td>
<td>26</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>100</td>
<td>86.8-100</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Neg</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Ind</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td>EIA NR<sup>2</sup></td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td><strong>Normal ALT and No Liver Histopathology</strong></td>
<td>2</td>
<td>1</td>
<td>0</td>
<td>1</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>50.0</td>
<td>1.3-98.7</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Pos</td>
<td>2</td>
<td>1</td>
<td>0</td>
<td>1</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>50.0</td>
<td>1.3-98.7</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Neg</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Ind</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td>EIA NR<sup>2</sup></td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td colspan="10"><strong>At Risk</strong></td>
</tr>
<tr class="odd">
<td><strong>Total</strong></td>
<td>1175</td>
<td>769</td>
<td>8</td>
<td>66</td>
<td>332</td>
<td>97.6</td>
<td>95.4-99.0</td>
<td>92.1</td>
<td>90.1-93.8</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Pos</td>
<td>831</td>
<td>765</td>
<td>0</td>
<td>66</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>92.1</td>
<td>90.0-93.8</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Neg</td>
<td>2</td>
<td>1<sup>1</sup></td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>100</td>
<td>2.5- 100</td>
<td>100</td>
<td>2.5- 100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Ind</td>
<td>7</td>
<td>3<sup>1</sup></td>
<td>0</td>
<td>0</td>
<td>4<sup>3</sup></td>
<td>100</td>
<td>39.8- 100</td>
<td>100</td>
<td>29.2- 100</td>
</tr>
<tr class="odd">
<td>EIA NR<sup>2</sup></td>
<td>335</td>
<td>0</td>
<td>8</td>
<td>0</td>
<td>327</td>
<td>97.6</td>
<td>95.3-99.0</td>
<td>N/A</td>
<td>N/A</td>
</tr>
</tbody>
</table>

> VERS = VERSANT Ser = Serology R = Reactive NR = Nonreactive Pos =
> Positive\
> Neg = Negative Agree = Agreement N/A = Insufficient data for
> meaningful result\
> Ind = Indeterminate\
> ^1^Subject was designated infected per CDC guidelines if RIBA was
> indeterminate or negative,\
> and PCR was positive.\
> ^2^Patients who had anti-HCV EIA non-reactive results were studied for
> approximating the\
> specificity of the AMPLICOR HCV Test, v2.0, but these data do not
> imply\
> performance for testing of anti-HCV EIA non-infected individuals.
>
> ^3^Subject was designated as having uncertain infection per CDC
> guidelines if RIBA was\
> indeterminant and PCR was negative.

### Comparison with PCR {#comparison-with-pcr .unnumbered}

As shown in Table XI-2, performance of the VERSANT HCV RNA Qualitative
Assay compared to an FDA-cleared PCR test was similar for each
population and overall. Of the 1,013 anti-HCV serology positive
specimens, HCV RNA was detected in 921 specimens by both assays (99.7%
positive Agreement) and not in 83 specimens (91.2% Negative Agreement).
The VERSANT HCV RNA Qualitative Assay was in 100% agreement with PCR for
specimens with indeterminate or negative RIBA results. The VERSANT HCV
RNA Qualitative Assay and the PCR test detected HCV RNA in 4 of 10
specimens with indeterminate RIBA results and in 1 of 6 specimens with
RIBA negative results. Of the 471 anti-HCV serology negative specimens,
both assays detected HCV RNA in 6 EIA nonreactive specimens, but not in
459 EIA nonreactive specimens.

Of the 522 VERSANT HCV RNA Qualitative Assay and PCR test results for
subjects with anti-HCV and biochemical or histological evidence of liver
disease, 520 (99.6%) were in agreement between the two assays: (a) 373
(100%) of 373 specimens from subjects with elevated ALT and liver
histopathology, (b) 121 (98.4%) of 123 specimens from subjects with
normal ALT and liver histopathology, and (c) 26 (100%) of 26 specimens
from subjects with elevated ALT and no liver histopathology. Both assays
were in 100% agreement for specimens with indeterminate or negative RIBA
results. The HCV TMA Assay and the PCR test detected HCV RNA in 2 of 4
specimens with indeterminate RIBA results and in 1 of 4 specimens with
RIBA negative results. Of the 126 specimens collected from subjects
without anti-HCV, 125 (99.2%) were in agreement. Both assays detected
HCV RNA in 1 EIA nonreactive specimen, but not in 124 EIA nonreactive
specimens.

Of the 830 VERSANT HCV RNA Qualitative Assay and PCR test results for
subjects at risk for HCV infection with anti-HCV, 824 (99.3%) were in
agreement between the two assays. Both assays detected HCV RNA in 759
specimens, but not in 65 specimens. Furthermore, both assays were in
100% agreement for specimens with indeterminate or negative RIBA
results. The VERSANT HCV RNA Qualitative Assay and the PCR test detected
HCV RNA in 3 of 7 specimens with indeterminate RIBA results and in 1 of
2 specimens with RIBA negative results. Of the 325 specimens collected
from subjects at risk for HCV infection without anti-HCV, 321 (98.8%)
were in agreement. Of the 325 anti-HCV serology negative specimens from
subjects at risk for HCV infection, both assays detected HCV RNA in 5
EIA nonreactive specimens, but not in 316 EIA nonreactive specimens.

<table>
<colgroup>
<col style="width: 17%" />
<col style="width: 6%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 9%" />
<col style="width: 10%" />
<col style="width: 10%" />
</colgroup>
<tbody>
<tr class="odd">
<td colspan="10"><strong>Table XI-2. Agreement of the VERSANT HCV RNA
Qualitative Assay and PCR for Each Study Population</strong></td>
</tr>
<tr class="even">
<td></td>
<td><strong>N</strong></td>
<td><p><strong>VERSANT+</strong></p>
<p><strong>PCR+</strong></p></td>
<td><p><strong>VERSANT+</strong></p>
<p><strong>PCR-</strong></p></td>
<td><p><strong>VERSANT-</strong></p>
<p><strong>PCR+</strong></p></td>
<td><p><strong>VERSANT-</strong></p>
<p><strong>PCR-</strong></p></td>
<td><strong>% Negative Agreement</strong></td>
<td><p><strong>95%</strong></p>
<p><strong>C.I.</strong></p></td>
<td><strong>% Positive Agreement</strong></td>
<td><p><strong>95%</strong></p>
<p><strong>C.I.</strong></p></td>
</tr>
<tr class="odd">
<td><strong>Total</strong></td>
<td>1500<sup>1</sup></td>
<td>932</td>
<td>12</td>
<td>3</td>
<td>553</td>
<td>97.9</td>
<td>96.3-98.9</td>
<td>99.7</td>
<td>99.1-99.9</td>
</tr>
<tr class="even">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td><strong>Anti-HCV Serology</strong></td>
<td>1500</td>
<td>932</td>
<td>12</td>
<td>3</td>
<td>553</td>
<td>97.9</td>
<td>96.3-98.9</td>
<td>99.7</td>
<td>99.1-99.9</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Pos</td>
<td>1013</td>
<td>921</td>
<td>8</td>
<td>1</td>
<td>83</td>
<td>91.2</td>
<td>83.4-96.1</td>
<td>99.9</td>
<td>99.4-100</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Neg</td>
<td>6</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>5</td>
<td>100</td>
<td>47.8-100</td>
<td>100</td>
<td>2.5-100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Ind</td>
<td>10</td>
<td>4</td>
<td>0</td>
<td>0</td>
<td>6</td>
<td>100</td>
<td>54.1-100</td>
<td>100</td>
<td>39.8-100</td>
</tr>
<tr class="odd">
<td>EIA NR<sup>2</sup></td>
<td>471</td>
<td>6</td>
<td>4</td>
<td>2</td>
<td>459</td>
<td>99.1</td>
<td>97.8-99.8</td>
<td>75.0</td>
<td>34.9-96.8</td>
</tr>
<tr class="even">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td colspan="10"><strong>Anti-HCV Serology, ALT, Liver Histological
Findings</strong></td>
</tr>
<tr class="even">
<td><strong>Total</strong></td>
<td>658</td>
<td>489</td>
<td>3</td>
<td>0</td>
<td>166</td>
<td>98.2</td>
<td>94.9-99.6</td>
<td>100</td>
<td>99.2-100</td>
</tr>
<tr class="odd">
<td><strong>Elevated ALT and Liver Histopathology</strong></td>
<td>425</td>
<td>371</td>
<td>0</td>
<td>0</td>
<td>54</td>
<td>100</td>
<td>93.4-100</td>
<td>100</td>
<td>99.0-100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Pos</td>
<td>373</td>
<td>368</td>
<td>0</td>
<td>0</td>
<td>5</td>
<td>100</td>
<td>47.8-100</td>
<td>100</td>
<td>99.0-100</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Neg</td>
<td>3</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>2</td>
<td>100</td>
<td>15.8-100</td>
<td>100</td>
<td>2.5-100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Ind</td>
<td>3</td>
<td>2</td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>100</td>
<td>2.5-100</td>
<td>100</td>
<td>15.8-100</td>
</tr>
<tr class="odd">
<td>EIA NR<sup>2</sup></td>
<td>46</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>46</td>
<td>100</td>
<td>92.3-100</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td><strong>Normal ALT and Liver Histopathology</strong></td>
<td>205</td>
<td>91</td>
<td>3</td>
<td>0</td>
<td>111</td>
<td>97.4</td>
<td>92.5-99.5</td>
<td>100</td>
<td>96.0-100</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Pos</td>
<td>123</td>
<td>90</td>
<td>2</td>
<td>0</td>
<td>31</td>
<td>93.9</td>
<td>79.8-99.3</td>
<td>100</td>
<td>96.0-100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Neg</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>100</td>
<td>2.5-100</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Ind</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>100</td>
<td>2.5-100</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td>EIA NR<sup>2</sup></td>
<td>80</td>
<td>1</td>
<td>1</td>
<td>0</td>
<td>78</td>
<td>98.7</td>
<td>93.1-100</td>
<td>100</td>
<td>2.5-100</td>
</tr>
<tr class="odd">
<td><strong>Elevated ALT and No Liver Histopathology</strong></td>
<td>26</td>
<td>26</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>100</td>
<td>86.8-100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Pos</td>
<td>26</td>
<td>26</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>100</td>
<td>86.8-100</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Neg</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Ind</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td>EIA NR<sup>2</sup></td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td><strong>Normal ALT and No Liver Histopathology</strong></td>
<td>2</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>100</td>
<td>2.5-100</td>
<td>100</td>
<td>2.5-100</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Pos</td>
<td>2</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>100</td>
<td>2.5-100</td>
<td>100</td>
<td>2.5-100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Neg</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Ind</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="even">
<td>EIA NR<sup>2</sup></td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>0</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
<td>N/A</td>
</tr>
<tr class="odd">
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td colspan="10"><strong>At Risk</strong></td>
</tr>
<tr class="odd">
<td><strong>Total</strong></td>
<td>1164</td>
<td>768</td>
<td>7</td>
<td>3</td>
<td>386</td>
<td>98.2</td>
<td>96.4-99.3</td>
<td>99.6</td>
<td>98.9-99.9</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Pos</td>
<td>830</td>
<td>759</td>
<td>5</td>
<td>1</td>
<td>65</td>
<td>92.9</td>
<td>84.1-97.6</td>
<td>99.9</td>
<td>99.3-100</td>
</tr>
<tr class="odd">
<td>EIA R / RIBA Neg</td>
<td>2</td>
<td>1</td>
<td>0</td>
<td>0</td>
<td>1</td>
<td>100</td>
<td>2.5-100</td>
<td>100</td>
<td>2.5-100</td>
</tr>
<tr class="even">
<td>EIA R / RIBA Ind</td>
<td>7</td>
<td>3</td>
<td>0</td>
<td>0</td>
<td>4</td>
<td>100</td>
<td>39.8-100</td>
<td>100</td>
<td>29.2-100</td>
</tr>
<tr class="odd">
<td>EIA NR<sup>2</sup></td>
<td>325</td>
<td>5</td>
<td>2</td>
<td>2</td>
<td>316</td>
<td>99.4</td>
<td>97.7-99.9</td>
<td>71.4</td>
<td>29.0-96.3</td>
</tr>
</tbody>
</table>

> VERS = VERSANT R = Reactive NR = Nonreactive Pos = Positive Neg =
> Negative\
> Agree = Agreement N/A = Insufficient data for meaningful result Ind =
> Indeterminate\
> N/A = Insufficient data for meaningful result

### Clinical Specimen Storage Study {#clinical-specimen-storage-study .unnumbered}

Specimen storage conditions were evaluated for their effects on assay
performance. Specimens from each of 72 subjects were separated into two
aliquots. One aliquot was stored at 2° to 8°C and tested within 48
hours. The other aliquot was stored frozen at -20°C or below for up to
44 days. Data indicated no difference in the detection of HCV RNA in
specimens stored in the two conditions.

### Signal Analysis {#signal-analysis .unnumbered}

A summary of the VERSANT HCV RNA Qualitative Assay signal analysis for
the assay calibrators and controls and the internal control in plasma
and serum specimens is shown in the table below:

  ------------ ----- ------------ --------- --------- ---------- ----------
  Calibrator   N     Mean RLU\    SD\       \% CV     Min RLU (x Max RLU (x
                     (x 1000)     (x 1000)            1000)      1000)

  Positive     111   1,265        102       8.0       795        1493

  Negative     110   5.6          3.0       53.2      0          13.1

                                                                 

  Control      N     Mean S/CO    SD        \% CV     Min S/CO   Max S/CO

  Positive     54    22.5         2.1       9.5       11.2       27.3

  Negative     54    0.07         0.04      55.1      0.01       0.2

  3                                                              

  Internal     N     Mean IC S/CO SD        %CV       Min S/CO   Max S/CO
  Control                                                        

  Serum        355   2.1          0.1       6.1       1.0        3.0

  Plasma       210   2.1          0.09      4.3       1.7        2.2
  ------------ ----- ------------ --------- --------- ---------- ----------

## REPRODUCIBILITY {#reproducibility .unnumbered}

Reproducibility testing was performed at three laboratories (A, B, C) to
obtain measures of repeatability and reproducibility during the clinical
trial; two of the sites were outside laboratories and one was in-house.
Testing was also conducted in-house during the preclinical phase (D). In
the clinical testing, the three sites were provided with six identical
panels of eight samples containing 0 to 9,615 IU/mL (0 to 50,000
copies/mL) genotype 1 or 0 to 577 IU/mL (0 to 3,000 copies/mL) genotype
2b in serum or plasma. In the preclinical phase testing, six member
serum or plasma panels for genotype 1 at 0 to 14.4 IU/mL (0 to 75
copies/mL) and genotype 2b at 0 to 69.2 IU/mL (0 to 360 copies/mL) were
tested. At sites A, B, and C, each of two operators performed two days
of testing with each of three kit lots for a total of six days of
testing. At Site D, three operators tested the genotype 1 panel with
each of three kit lots on six separate days. Similarly, Site D tested
the genotype 2b panel with each of three kit lots on each of five
separate days. Reproducibility testing at or near the assay's limit of
detection was not done with genotypes other than genotype 1. The data is
presented in the package insert.

## CONCLUSIONS DRAWN FROM STUDIES

## Risk/Benefit Analysis {#riskbenefit-analysis .unnumbered}

As a nucleic acid and amplification assay, the VERSANT HCV RNA
Qualitative Assay detects the presence of HCV RNA in human plasma or
serum. Detection of viral nucleic acid is indicative of viral
replication and therefore, active HCV infection. The primary benefit of
using this test is the detection of active HCV infection in individuals
with antibody evidence of HCV infection with evidence of liver disease,
and individuals suspected to be actively infected with HCV with antibody
evidence, and individuals at risk for HCV infection with antibodies to
HCV.

The potential risks seen for *in vitro* diagnostic assays are not
unusual in the laboratory setting, and appropriate warnings and risks
are contained in the labeling for these devices. Standard good
laboratory practices are recommended to minimize the risks to the end
user. The benefits to patients tested with the VERSANT HCV RNA
Qualitative Assay exceed the known or potential risks or adverse events
for patients or laboratory personnel.

## Safety {#safety .unnumbered}

The VERSANT HCV RNA Qualitative Assay is a diagnostic test that utilizes
blood specimens and, as such, requires the withdrawal of blood from
individuals being tested. The safety hazards to individuals being tested
are no greater than those involved in other diagnostic tests for which
blood is drawn.

## PANEL RECOMMENDATIONS

Pursuant to Section 515(c)(2) of the act as amended by the Safe Medical
Devices Act of 1990, this PMA was not the subject of an FDA Microbiology
Devices Advisory Panel meeting because the information in the PMA
substantially duplicated information previously reviewed by the Panel.

## CDRH DECISION

The applicant's manufacturing facility inspected on ­­­­­­ was found to be in
compliance with the Quality Systems Regulation (21 CFR 820).

FDA issued an approval order on November 7, 2002.

## APPROVAL SPECIFICATIONS

Directions for use: See Labeling

Hazards to Health from Use of the Device: See Indications,
Contraindications, Warning, precautions and Adverse Events in the
labeling.

Postapproval Requirements and Restrictions: See approval order.