ORAQUICK HCV RAPID ANTIBODY TEST
Device Facts
| Record ID | P080027S001 |
|---|---|
| Device Name | ORAQUICK HCV RAPID ANTIBODY TEST |
| Applicant | OraSure Technologies, Inc. |
| Product Code | MZO · Microbiology |
| Decision Date | Feb 18, 2011 |
| Decision | APPR |
| Regulation | 21 CFR 866.3169 |
| Device Class | Class 2 |
Indications for Use
The OraQuick® HCV Rapid Antibody Test is a single-use immunoassay for the qualitative detection of antibodies to hepatitis C virus (anti-HCV) in fingerstick whole blood specimens and venipuncture whole blood specimens (EDTA, sodium heparin, lithium heparin, and sodium citrate) from individuals 15 years or older. The OraQuick® HCV Rapid Antibody Test results, in conjunction with other laboratory results and clinical information, may be used to provide presumptive evidence of infection with HCV (state of infection or associated disease not determined) in persons with signs or symptoms of hepatitis and in persons at risk for hepatitis C infection.
Device Story
Single-use lateral flow immunoassay; detects antibodies to HCV structural/non-structural proteins (core, NS3, NS4). Input: fingerstick or venipuncture whole blood. Mechanism: synthetic peptides/recombinant antigens immobilized on assay strip; colloidal gold-labeled protein A binds anti-HCV antibodies to generate visible test line. Includes procedural control line. Used in clinical settings; operated by healthcare professionals. Output: visual qualitative result (reactive/non-reactive). Results provide presumptive evidence of infection; require follow-up with supplemental tests (PCR, SIA) for confirmation. Benefits: rapid identification of potential HCV infection to facilitate clinical assessment and management.
Clinical Evidence
Clinical performance evaluated in two prospective multi-center studies (n=1207 venous; n=1660 fingerstick). Venous blood: 99.5% positive agreement, 99.0% negative agreement. Fingerstick blood: 97.9% positive agreement, 98.5% negative agreement. Comparator: EIA with supplemental RIBA/PCR. No adverse events reported. Bench testing confirmed performance across genotypes 1-4, seroconversion panels, and interfering substances.
Technological Characteristics
Lateral flow immunoassay; utilizes synthetic peptides and recombinant antigens (core, NS3, NS4 regions) immobilized on nitrocellulose strip. Detection via colloidal gold-labeled protein A. Housing: plastic (Top PN 3001-1745, Base PN 3001-1746). Manual visual read. Shelf life: 18 months at 2-30°C. Kit includes developer solution, specimen collection loops, and test stand.
Indications for Use
Indicated for qualitative detection of anti-HCV antibodies in fingerstick or venipuncture whole blood from individuals 15 years or older. Used for presumptive evidence of HCV infection in symptomatic persons or those at risk for hepatitis C.
Regulatory Classification
Identification
A hepatitis C virus (HCV) antibody test is identified as an in vitro diagnostic device intended for use with human serum, plasma, or other matrices as a prescription device that aids in the diagnosis of HCV infection in persons with signs and symptoms of hepatitis and in persons at risk for hepatitis C infection. The test is not intended for screening blood, plasma, cell, or tissue donors.
Special Controls
*Classification.* Class II (special controls). The special controls for this device are:(1) The labeling required under § 809.10(b) of this chapter must include: (i) A prominent statement that the test is not intended for the screening of blood, plasma, and cell or tissue donors. (ii) Limitations, which must be updated to reflect current clinical practice and disease presentation and management. The limitations must include, but are not limited to, statements that indicate: (A) When appropriate, the performance characteristics of the test have not been established in populations of immunocompromised or immunosuppressed patients or, other special populations where test performance may be affected. (B) The detection of HCV antibodies indicates a present or past infection with hepatitis C virus, but does not differentiate between acute, chronic, or resolved infection. (C) The specimen types for which the device has been cleared, and that use of the test with specimen types other than those specifically cleared for this device may result in inaccurate test results. (D) Test results are to be interpreted by qualified licensed healthcare professionals in conjunction with the individual's clinical presentation, history, and other laboratory results. (E) A non-reactive test result may occur early during acute infection, prior to development of a host antibody response to infection, or when analyte levels are below the limit of detection of the test. (iii) A detailed explanation of the principles of operation and procedures for performing the test. (2) Design verification and validation must include the following: (i) A detailed device description, including all parts that make up the device, ancillary reagents required but not provided, an explanation of the device methodology, and design of the antigen(s) and capture antibody(ies) sequences, rationale for the selected epitope(s), degree of amino acid sequence conservation of the target, and the design and nature of all primary, secondary, and subsequent standards used for calibration. (ii) Documentation and characterization ( *e.g.,* supplier, determination of identity, and stability) of all critical reagents (including description of the antigen(s) and capture antibody(ies)), and protocols for maintaining product integrity throughout its labeled shelf life.(iii) Risk analysis and management strategies, such as Failure Modes Effects Analysis and/or Hazard Analysis and Critical Control Points summaries and their impact on test performance. (iv) Final release criteria to be used for manufactured test lots with appropriate evidence that lots released at the extremes of the specifications will meet the claimed analytical and clinical performance characteristics as well as the stability claims. (v) Stability studies for reagents must include documentation of an assessment of real-time stability for multiple reagent lots using the indicated specimen types and must use acceptance criteria that ensure that analytical and clinical performance characteristics are met when stability is assigned based on the extremes of the acceptance range. (vi) All stability protocols, including acceptance criteria. (vii) Final release test results for each lot used in clinical studies. (viii) Multisite reproducibility study that includes the testing of three independent production lots. (ix) Analytical performance studies and results for determining the limit of blank (LoB), limit of detection (LoD), cutoff, precision (reproducibility) including lot-to-lot and/or instrument-to-instrument precision, interference, cross reactivity, carryover, hook effect, seroconversion panel testing, matrix equivalency, specimen stability, reagent stability, and cross-genotype antibody detection sensitivity, when appropriate. (x) Analytical sensitivity of the test is the same or better than that of other cleared or approved tests. (xi) Detailed documentation of clinical performance testing from a multisite clinical study. Performance must be analyzed relative to an FDA cleared or approved HCV antibody test, or a comparator that FDA has determined is appropriate. This study must be conducted using appropriate patient samples, with an acceptable number of HCV positive and negative samples in applicable risk categories. Additional relevant patient groups must be validated as appropriate. The samples may be a combination of fresh and repository samples, sourced from geographically diverse areas. The study designs, including number of samples tested, must be sufficient to meet the following criteria: (A) Clinical sensitivity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 95 percent. (B) Clinical specificity of the test must have a lower bound of the 95 percent confidence interval of greater than or equal to 96 percent. (3) For any HCV antibody test intended for Point of Care (PoC) use, the following special controls, in addition to those listed in paragraphs (b)(1) and (2) of this section, apply: (i) Clinical studies must be conducted at PoC sites. (ii) Additional labeling must include a brief summary of the instructions for use that are appropriate for use in a PoC environment.
Submission Summary (Full Text)
{0}
# SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)
# I. GENERAL INFORMATION
Device Generic Name: Antibody to Hepatitis C Virus (Anti-HCV) Rapid Assay
Device Trade Name: OraQuick® HCV Rapid Antibody Test
Applicant's Name and Address: OraSure Technologies, Inc.
220 East First Street
Bethlehem, PA 18015
Date of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P080027/S001
Date of FDA Notice of Approval: February 18, 2011
Expedited: Not Applicable
The original PMA (P080027) was approved on 06/25/2010 and is indicated for "The OraQuick® HCV Rapid Antibody Test is a single-use immunoassay for the qualitative detection of antibodies to hepatitis C virus (anti-HCV) in venipuncture whole blood specimens (EDTA, sodium heparin, lithium heparin, and sodium citrate) from individuals 15 years or older. The OraQuick® HCV Rapid Antibody Test results, in conjunction with other laboratory results and clinical information, may be used to provide presumptive evidence of infection with HCV (state of infection or associated disease not determined) in persons with signs or symptoms of hepatitis and in persons at risk for hepatitis C infection." The current supplement was submitted to expand the indication for the OraQuick® HCV Rapid Antibody Test to the use of fingerstick whole blood in the assay.
# II. INDICATIONS FOR USE
The OraQuick® HCV Rapid Antibody Test is a single-use immunoassay for the qualitative detection of antibodies to hepatitis C virus (anti-HCV) in fingerstick whole blood specimens and venipuncture whole blood specimens (EDTA, sodium heparin, lithium heparin, and sodium citrate) from individuals 15 years or older. The OraQuick® HCV Rapid Antibody Test results, in conjunction with other laboratory results and clinical information, may be used to provide presumptive evidence of infection with HCV (state of infection or associated disease not determined) in persons with signs or symptoms of hepatitis and in persons at risk for hepatitis C infection.
# CONTRAINDICATIONS
None
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 1
5
{1}
### III. WARNINGS AND PRECAUTIONS
The warnings and precautions can be found in the OraQuick® HCV Rapid Antibody Test labeling.
### IV. DEVICE DESCRIPTION
The OraQuick® HCV Rapid Antibody Test kit is comprised of a divided pouch containing a test device with an absorbent packet and a labeled developer solution vial. Also included in the kits are reusable test stands, single use specimen collection loops, and a package insert.
The OraQuick® HCV Rapid Antibody Test utilizes an indirect lateral flow immunoassay method to detect antibodies to both structural and non-structural HCV proteins. The device utilizes synthetic peptides and recombinant antigens from the core, NS3, and NS4 regions of the HCV genome, that are immobilized as a single test line on the assay strip. Antibodies reacting with these peptides and antigens are visualized by colloidal gold labeled with protein A generating a visible line in the test zone for a reactive sample. The device also includes a built-in procedural control that demonstrates assay validity. A reddish-purple line in this Control Zone (C Zone) must appear for a test result to be valid, whether or not the sample is reactive or non-reactive for anti-HCV.
The OraQuick® HCV Rapid Antibody Test Kit Controls are available separately for use only with the OraQuick® HCV Rapid Antibody Test. The Kit Controls are human plasma-based reagents and are specifically formulated and manufactured to ensure proper performance of the test. The HCV Positive Control will produce a reactive reddish-purple line at the Test Zone (T Zone). The HCV Negative Control will generate a non-reactive
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 2
{2}
test result (no reddish-purple line at the T Zone). Use of kit control reagents manufactured by any other source may not meet the requirements for an adequate quality assurance program for the OraQuick® HCV Rapid Antibody Test.
# V. ALTERNATIVE PRACTICES AND PROCEDURES
There are several other alternatives for the detection of antibodies to HCV. Each alternative has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.
Determination of the presence of anti-HCV in patients may be achieved by using a variety of commercially available FDA approved serological tests. Anti-HCV test results are used in combination with a physician's assessment and other laboratory test results, in order to establish a diagnosis of infection with HCV.
# VI. MARKETING HISTORY
The product has been commercialized in the countries comprising the European Union. This product has not been withdrawn from any market for any reason. The (device) has not been marketed in the United States with the whole blood fingerstick specimen claim.
# VII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH
Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device.
A false positive result using an anti-HCV test would not be considered a patient or public health concern since a reactive result would be followed-up with supplemental tests, e.g., polymerase chain reaction (PCR) for detection of HCV RNA and/or strip immunoblot assay (SIA) to confirm infection and/or determine disease state. Treatment of the patient with chronic HCV infection is initiated only after extensive clinical, laboratory and behavioral assessment in order to assess eligibility and ability to comply with therapy.
A false negative anti-HCV result in a diagnostic setting may cause an HCV infected patient to remain undetected. This could be a safety concern for both the patient and the public, since such individuals may be capable of transmitting HCV infection. However, in patients where the suspicion of HCV infection is high, HCV RNA testing is often used to identify viremic individuals.
There were no adverse events that occurred in the clinical studies.
# VIII. SUMMARY OF PRECLINICAL STUDIES
The performance characteristics of the OraQuick® HCV Rapid Antibody Test were evaluated in the non-clinical studies performed at OraSure Technologies, Inc.
# A. Laboratory Studies
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 3
7
{3}
# Biocompatibility
The OraQuick® HCV device housing biocompatibility testing was completed by NAMSA (North American Science Associates) located at 6750 Wales Road, Northwood, Ohio. All testing was compliant with FDA Good Laboratory Practice (GLP) Requirements 21 CFR part 58. All testing used the OraQuick® HCV device housings (Top PN 3001-1745 and Base PN 3001-1746).
# Reactivity with HCV Seroconversion Panels
Eighteen panels containing sequential plasma specimens from individuals undergoing seroconversion as a result of HCV infection were evaluated with the OraQuick® HCV Rapid Antibody Test and compared with an FDA approved anti-HCV EIA test. The OraQuick® HCV Rapid Antibody Test and the reference anti-HCV assay results are summarized in the following table. The sensitivity of the OraQuick® HCV Rapid Antibody Test to detect seroconversion was similar to that of the comparator EIA. The OraQuick® HCV Rapid Antibody Test detected anti-HCV antibodies earlier than the EIA in 9 of the 18 seroconversion panels (50%) and by an overall average of 3.6 days (95% CI = 1.2 to 5.9).
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 4
8
{4}
| Seroconversion Panel | Days to Evidence of HCV Infection | | | | |
| --- | --- | --- | --- | --- | --- |
| | OraQuick® HCV Rapid Antibody Test | | FDA approved anti-HCV EIA | | Difference (OraQuick® - EIA) First Reactive |
| | Last Non-Reactive | First Reactive | Last Non-Reactive | First Reactive | |
| HCV 6213 | 35 | 37 | 30 | 37 | 0 |
| HCV 6214 | 18 | 23 | 23 | 25 | -2 |
| HCV 6227 | 46 | 74 | 46 | 74 | 0 |
| HCV 9041 | 31 | 62 | 31 | 62 | 0 |
| HCV 9046 | 0 | 69 | 0 | 69 | 0 |
| HCV 9047 | 21 | 28 | 21 | 28 | 0 |
| PHV 901 | 65 | 97 | 65 | 97 | 0 |
| PHV 905 | 7 | 11 | 11 | 18 | -7 |
| PHV 907 | 7 | 13 | 13 | 18 | -5 |
| PHV 910 (M) | 0 | 4 | 0 | 4 | 0 |
| PHV 911 (M) | 0 | 11 | 0 | 11 | 0 |
| PHV 914 | 9 | 12 | 19 | 24 | -12 |
| PHV 916 (M) | 7 | 9 | 9 | 23 | -14 |
| PHV 917 (M) | 22 | 85 | 22 | 85 | 0 |
| PHV 920 | 7 | 13 | 7 | 16 | -3 |
| PHV 921 | 0 | 4 | 4 | 14 | -10 |
| RP 006 | 388 | 461 | 461 | 469 | -8 |
| RP 038 | 47 | 52 | 52 | 55 | -3 |
| Average | | 59.2 | | 62.7 | -3.6 (-5.9 to -1.2) |
Reactivity with HCV Specimens from Various Genotypes and Subtypes
The ability of the OraQuick® HCV Rapid Antibody Test to detect infection derived from various genotypes and subtypes was assessed using two commercially available Worldwide HCV Performance panels. Thirty-two HCV-positive plasma specimens derived from multiple geographic regions, representing four genotypes (1, 2, 3 and 4) were tested. All specimens were reactive with the OraQuick® HCV Rapid Antibody Test. Three HCV-negative samples were included in the panel and all were non-reactive with the OraQuick® HCV Rapid Antibody Test.
### Interfering Substances
The OraQuick® HCV Rapid Antibody Test was evaluated with the following interfering substances present in whole blood samples in order to assess their potential effect on the assay performance as per CLSI guidelines EP7-A2. Testing was completed on ten HCV-negative whole blood samples and ten HCV-positive spiked matched whole blood samples. All matched samples were spiked according to one of the following conditions as per the table below:
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 5
9
{5}
| Interfering Substances | Concentration |
| --- | --- |
| Bilirubin | 10 mg/dL |
| Hemoglobin | 500 mg/dL |
| Lipid (Triolein) | 3500 mg/dL |
| Protein | 12 g/dL |
None of these interfering substances had any impact on the OraQuick® HCV Rapid Antibody Test assay performance at the concentrations evaluated.
Medical Conditions Unrelated to HCV Infection
The performance of the OraQuick® HCV Rapid Antibody Test was evaluated with commercially available HCV negative plasma and serum specimens derived from patients with medical conditions unrelated to HCV infection. Results are summarized in the table below.
| Medical Condition | | Non-Reactive (%) | Reactive (%) |
| --- | --- | --- | --- |
| **Autoimmune Diseases** N | | | |
| Myasthenia Gravis | 4 | 4 (100) | 0 (0) |
| Rheumatoid Arthritis | 10 | 10 (100) | 0 (0) |
| Systemic Lupus Erythematosus (SLE) | 10 | 10 (100) | 0 (0) |
| **Other Medical Conditions** | | | |
| Influenza Vaccination | 10 | 10 (100) | 0 (0) |
| Hepatitis A Virus (HAV) | 59 | 59 (100) | 0 (0) |
| Hepatitis B Virus (HBV) | 58 | 58 (100) | 0 (0) |
| Hepatitis D Virus (HDV) | 2 | 2 (100) | 0 (0) |
| Hepatitis E Virus (HEV) | 8 | 8 (100) | 0 (0) |
| Epstein-Barr Virus (EBV) | 10 | 10 (100) | 0 (0) |
| Cytomegalovirus (CMV) | 10 | 10 (100) | 0 (0) |
| Herpes Simplex Virus (HSV) | 10 | 10 (100) | 0 (0) |
| Parvovirus B19 | 10 | 10 (100) | 0 (0) |
| Rubella | 10 | 10 (100) | 0 (0) |
| Syphilis | 10 | 10 (100) | 0 (0) |
| Toxoplasmosis | 10 | 10 (100) | 0 (0) |
| Human Immunodeficiency Virus (HIV-1/2) | 154 | 154 (100) | 0 (0) |
| Heterophilic antibodies | 10 | 10 (100) | 0 (0) |
| Multiparous Female | 10 | 10 (100) | 0 (0) |
| **Total Samples Tested** | **405** | **405** | **0** |
None of the medical conditions tested produced false positive results in the OraQuick® HCV Rapid Antibody Test device. Performance characteristics in scleroderma, Sjögren's Syndrome and Human T-Cell Lymphotropic Virus (HTLV I/II) have not been established.
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 6
10
{6}
# Sample Stability
The OraQuick® HCV Rapid Antibody Test was evaluated with whole blood stored at various storage conditions over numerous days. Results are summarized in the table below.
| Specimen Type | Days at Storage Condition | |
| --- | --- | --- |
| | 2°-8°C (36°-46°F) | 15°-30°C (59°-86°F) |
| Whole Blood | 7 | 3 |
Storing whole blood for up to 7 days refrigerated or 3 days at 15°-30°C (59°-86°F) did not impact the performance of the OraQuick® HCV Rapid Antibody Test.
# Specimen Types
The OraQuick® HCV Rapid Antibody Test was evaluated with venipuncture whole blood samples collected in various types of anticoagulants including ethylenediaminetetraacetic acid (EDTA), sodium heparin, lithium heparin, and sodium citrate. Testing was performed with twenty anti-HCV negative whole blood samples and twenty anti-HCV-spiked positive whole blood samples. Venipuncture whole blood in all anticoagulants produced acceptable assay performance. The recommended sample collection devices for use with the OraQuick® HCV Rapid Antibody Test in whole blood are vacuum tubes containing EDTA, sodium heparin, lithium heparin, sodium citrate.
Fingerstick whole blood is also an acceptable specimen type.
# Limit of Detection Study
The limit of detection (LoD), defined as the EIA signal to cutoff ratio which yielded reactive results 95% of the time in the OraQuick® Rapid HCV Antibody Test device, was calculated for each of three (3) lots separately and for three (3) lots combined. Using values obtained with an FDA approved anti-HCV EIA, the LoD of the OraQuick® Rapid HCV Antibody Test for venous whole blood and fingerstick whole blood was calculated to be 0.75 and 0.89 s/co, respectively. This means that the OraQuick® HCV Rapid Antibody Test may provide a positive result where the comparator EIA is equivocal. Since the assay is visually read, the LoD may vary depending on the user (see tables below).
# Venous Whole Blood
Anti-HCV positive whole blood dilutions were tested by three (3) operators over a period of five (5) day with three (3) lots of devices. For each dilution, a total of forty-five (45) data points were generated overall, or fifteen (15) data points per each of the three (3) device lots. The tables below summarize the number of reactive or non-reactive results obtained for the anti-HCV positive whole blood dilutions per device lot, per operator and overall.
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 7
11
{7}
| OraQuick® HCV Device Test Results per Venous Whole Blood Dilution by Operator | | | | | |
| --- | --- | --- | --- | --- | --- |
| Plasma Dilution | Signal to Cutoff | Developer Dilution Assignment | Percent of Reactive Results per Operator | | |
| | | | Operator 1 | Operator 2 | Operator 3 |
| 1:160 | 1.85 | A | 100% (15/15) | 100% (15/15) | 100% (15/15) |
| 1:200 | 1.18 | B | 100% (15/15) | 100% (15/15) | 100% (15/15) |
| 1:400 | 0.80 | C | 100% (15/15) | 100% (15/15) | 100% (15/15) |
| 1:500 | 0.64 | D | 100% (15/15) | 53.3% (8/15) | 80.0% (12/15) |
| 1:600 | 0.50 | E | 100% (15/15) | 33.3% (5/15) | 66.7% (10/15) |
| OraQuick® HCV Device Test Results per Venous Whole Blood Dilution by Lot | | | | | |
| --- | --- | --- | --- | --- | --- |
| Plasma Dilution | Signal to Cutoff | Developer Dilution Assignment | Percent of Reactive Results per Lot | | |
| | | | Lot 1 | Lot 2 | Lot 3 |
| 1:160 | 1.85 | A | 100% (15/15) | 100% (15/15) | 100% (15/15) |
| 1:200 | 1.18 | B | 100% (15/15) | 100% (15/15) | 100% (15/15) |
| 1:400 | 0.80 | C | 100% (15/15) | 100% (15/15) | 100% (15/15) |
| 1:500 | 0.64 | D | 73.3% (11/15) | 73.3% (11/15) | 66.7% (10/15) |
| 1:600 | 0.50 | E | 66.7% (10/15) | 73.3% (11/15) | 60.0% (9/15) |
| Summary of OraQuick® HCV Device Test Results per Venous Whole Blood Dilution for all OraQuick® HCV Tests | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Plasma Dilution | Signal to Cutoff | Developer Dilution Assignment | Total Number of Tests | Number of Reactive Results | Number of Non-Reactive Results | Percent of Reactive Results |
| 1:160 | 1.85 | A | 45 | 45 | 0 | 100% |
| 1:200 | 1.18 | B | 45 | 45 | 0 | 100% |
| 1:400 | 0.80 | C | 45 | 45 | 0 | 100% |
| 1:500 | 0.64 | D | 45 | 32 | 13 | 71.1% |
| 1:600 | 0.50 | E | 45 | 30 | 15 | 66.7% |
Using an FDA approved anti-HCV EIA, the LoD for venous whole blood was calculated to be 0.75 s/co (by probit analysis).
### Fingerstick Whole Blood
Three operators took fingerstick whole blood from at least 30 individuals over a period of five days. The study verified the enrolled individuals to be HCV negative. Following
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 8
12
{8}
each fingerstick, the study directed each operator to place the whole blood into one of the dilutions, stir the solution, insert the investigational device into the solution, and finally read off the result. The operators had no knowledge of the dilution level. After a period of five days, the study resulted in 21 measurements taken at each dilution level, 7 measurements for each operator.
| OraQuick® HCV Device Test Results per Venous Whole Blood Dilution by Operator | | | | | |
| --- | --- | --- | --- | --- | --- |
| Plasma Dilution | Signal to Cutoff | Developer Dilution Assignment | Percent of Reactive Results per Operator | | |
| | | | Operator 1 | Operator 2 | Operator 3 |
| 1:160 | 1.85 | A | 100% (7/7) | 100% (7/7) | 100% (7/7) |
| 1:200 | 1.18 | B | 100% (7/7) | 100% (7/7) | 100% (7/7) |
| 1:400 | 0.80 | C | 71.4% (5/7) | 100% (7/7) | 100% (7/7) |
| 1:500 | 0.64 | D | 42.9% (3/7) | 42.9% (3/7) | 100% (7/7) |
| 1:600 | 0.50 | E | 0% (0/7) | 71.4% (5/7) | 71.4% (5/7) |
| Summary of OraQuick® HCV Device Test Results per Fingerstick Whole Blood Dilution for all OraQuick® HCV Tests | | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| Plasma Dilution | Signal to Cutoff | Developer Dilution Assignment | Total Number of Tests | Number of Reactive Results | Number of Non-Reactive Results | Percent of Reactive Results |
| 1:160 | 1.85 | A | 21 | 21 | 0 | 100% |
| 1:200 | 1.18 | B | 21 | 21 | 0 | 100% |
| 1:400 | 0.80 | C | 21 | 19 | 2 | 90.5% |
| 1:500 | 0.64 | D | 21 | 13 | 8 | 61.9% |
| 1:600 | 0.50 | E | 21 | 10 | 11 | 47.6% |
Using an FDA approved anti-HCV EIA, the LoD for fingerstick whole blood was calculated to be 0.89 s/co (by probit analysis).
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 9
13
{9}
# Reproducibility
The reproducibility of the OraQuick® HCV Rapid Antibody Test was tested at 3 sites using 3 lots of test devices twice a day for 5 days with 9 operators (3 per site). Three whole blood panel member types (negative, limit of detection (LoD), and low positive) were tested in 5 unique test kit types. Each test kit consisted of eight (8) blinded panel members that had various combinations of the 3 panel members in a randomized sequence. Panel members were blinded per operator, run, and device lot to ensure that the results of the panel member types were unpredictable to the operator. The LoD specimen was determined to be a 0.75 s/co by an FDA approved EIA. Overall concordance across operators, sites, and device lots was 98.9% for the negative specimen, 98.7% for the LoD specimen and 99.7% for the low positive specimen.
# Stability Studies
Two stability studies, comprised of three (3) validation lots each, are ongoing to evaluate the OraQuick® HCV Rapid Antibody Test shelf life and the OraQuick® HCV Rapid Antibody Test Kit Control shelf life. The OraQuick® HCV Rapid Antibody Test Kit Control study also includes an open vial stability evaluation.
The data from the stability study for the OraQuick® HCV Rapid Antibody Test substantiates a shelf life of eighteen (18) months at storage conditions of 2° - 30°C (36° - 86°F).
The data from the stability study for the OraQuick® HCV Rapid Antibody Test Kit Controls substantiates a twelve (12) month shelf life at storage conditions of 2° - 8°C (36° - 46°F). Once opened, the OraQuick® HCV Rapid Antibody Test Kit Controls have an eight (8) week shelf life at storage conditions of 2° - 8°C (36° - 46°F).
# Shipping Studies
The OraQuick® HCV Rapid Antibody Test (Pouched Assay – Device and Developer Solution) is packaged in 25-count or 100-count preprinted boxes including an equivalent number of loops for blood testing, reusable OraQuick® Test stands, and package insert.
A shipping study was performed to confirm that the external packaging configuration for the OraQuick® HCV Rapid Antibody Test provided a high probability of safe and intact arrival at its destination. The study was designed to confirm that the integrity of the packaging and its components could withstand the simulated shipping and handling stresses and to demonstrate that the shipping and handling stresses had no adverse effect on the OraQuick® HCV Rapid Antibody Test performance.
The OraQuick® HCV Rapid Antibody Test Kit Controls are comprised of an HCV Positive Control and an HCV Negative Control packaged in a Control Box with its Package Insert. The Control Box is then placed in an insulated outer shipping carton. A shipping study was performed to confirm that the external packaging configuration for the OraQuick® HCV Rapid Antibody Test Kit Controls provided a high probability of
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 10
14
{10}
safe and intact arrival at its destination. The study was designed to confirm that the integrity of the packaging and its components could withstand simulated shipping and handling stresses and to demonstrate that the shipping and handling stresses had no adverse effect on the OraQuick® HCV Rapid Antibody Test Kit Control performance.
# **B. Animal Studies**
Not Applicable
# **C. Additional Studies**
Not Applicable
# **IX. SUMMARY OF PRIMARY CLINICAL STUDY(IES)**
# **VENOUS WHOLE BLOOD**
# **Expected Results for the Intended Use Population**
Of the 1207 specimens tested in two OraQuick® HCV Rapid Antibody Test clinical studies of venipuncture whole blood, 88.2% (1064/1207) were from subjects at risk for hepatitis C infection but were asymptomatic and reported no current signs or symptoms of hepatitis, and 11.8% (142/1207) were from subjects with current signs or symptoms of hepatitis. One (1/1207) pregnant subject was enrolled without signs or symptoms of hepatitis or risk factors for hepatitis C infection. The 1207 individuals were enrolled from the following collection locations:
- 50.3% from Miami, FL
- 24.7% from Ft. Lauderdale, FL
- 13.6% from Fall River, MA
- 10.7% from Allentown, PA
- 0.7% from College Park, MD, San Francisco, CA, Dallas, TX, and Philadelphia, PA.
The OraQuick® HCV Rapid Antibody Test was reactive in 36.7% (443/1207) of subjects tested. There were no invalid OraQuick® HCV Rapid HCV Antibody Test results reported for the 1207 specimens tested (0/1207, 95% CI: 0.0%, 0.3%). Of the 1207 individuals tested, 33.1% (400/1207) were also self-reported HIV positive. The table below summarizes the distribution of OraQuick® HCV Rapid Antibody Test reactive, non-reactive, and invalid results for the 1207 specimens tested.
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 11
15
{11}
| Age Range | Gender | OraQuick® HCV Rapid Antibody Test Results in High Risk Individuals | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | No signs or symptoms | | | | Signs or symptoms | | | |
| | | Reactive | Non-Reactive | Invalid | Total (n) | Reactive | Non-Reactive | Invalid | Total (n) |
| | | n (%) | n (%) | n (%) | | n (%) | n (%) | n (%) | |
| 0-9 | F | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| | M | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| 10-19 | F | 0 (0.0) | 11 (1.0) | 0 (0.0) | 11 | 1 (0.7) | 1 (0.7) | 0 (0.0) | 2 |
| | M | 0 (0.0) | 14 (1.3) | 0 (0.0) | 14 | 0 (0.0) | 1 (0.7) | 0 (0.0) | 1 |
| 20-29 | F | 11 (1.0) | 29 (2.7) | 0 (0.0) | 40 | 1 (0.7) | 9 (6.3) | 0 (0.0) | 10 |
| | M | 7 (0.7) | 50 (4.7) | 0 (0.0) | 57 | 1 (0.7) | 3 (2.1) | 0 (0.0) | 4 |
| 30-39 | F | 15 (1.4) | 44 (4.1) | 0 (0.0) | 59 | 4 (2.8) | 18 (12.7) | 0 (0.0) | 22 |
| | M | 23 (2.2) | 56 (5.3) | 0 (0.0) | 79 | 4 (2.8) | 4 (2.8) | 0 (0.0) | 8 |
| 40-49 | F | 53 (5.0) | 97 (9.1) | 0 (0.0) | 150 | 7 (4.9) | 8 (5.6) | 0 (0.0) | 15 |
| | M | 82 (7.7) | 191 (18.0) | 0 (0.0) | 273 | 6 (4.2) | 8 (5.6) | 0 (0.0) | 14 |
| 50-59 | F | 41 (3.9) | 38 (3.6) | 0 (0.0) | 79 | 3 (2.1) | 5 (3.5) | 0 (0.0) | 8 |
| | M | 137 (12.9) | 117 (11.0) | 0 (0.0) | 254 | 23 (16.2) | 9 (6.3) | 0 (0.0) | 32 |
| 60-69 | F | 6 (0.6) | 5 (0.5) | 0 (0.0) | 11 | 1 (0.7) | 9 (6.3) | 0 (0.0) | 10 |
| | M | 13 (1.2) | 19 (1.8) | 0 (0.0) | 32 | 2 (1.4) | 5 (3.5) | 0 (0.0) | 7 |
| 70-79 | F | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 4 (2.8) | 0 (0.0) | 4 |
| | M | 1 (0.1) | 4 (0.4) | 0 (0.0) | 5 | 1 (0.7) | 2 (1.4) | 0 (0.0) | 3 |
| 80-89 | F | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 1 (0.7) | 0 (0.0) | 1 |
| | M | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 1 (0.7) | 0 (0.0) | 1 |
| 90-100 | F | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| | M | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| Total (N)* | | 389 (36.6) | 675 (63.4) | 0 (0.0) | 1064 | 54 (38.0) | 88 (62.0) | 0 (0.0) | 142 |
- Does not include one pregnant woman enrolled without signs or symptoms of hepatitis or at risk for hepatitis C infection.
### Venous Whole Blood Clinical Performance.
Two multi-center prospective studies were conducted to evaluate the clinical performance of the OraQuick® HCV Rapid Antibody Test in subjects with signs or symptoms of hepatitis and subjects at risk for hepatitis C infection. These risk factors included past or present intravenous drug use, having received a blood transfusion or organ transplant prior to 1992, evidence of high-risk sexual behavior, being born to an HCV positive mother, having been on long-term hemodialysis, history of incarceration, and positive for HIV. Clinical performance was evaluated in venipuncture whole blood specimens from subjects prospectively enrolled at 8 geographically dispersed centers within the United States.
The population tested was African American (43.0%), Caucasian (37.7%), Hispanic/Latino (17.1%), as well as a small proportion of other ethnic groups (2.2%). The mean age was 45 years (age range: 15 to 84 years). Of the 1207 subject specimens tested, 436 were HCV infected, 762 were negative, and 9 specimens had the status of "Unable to Determine". HCV status was determined for each subject by EIA, with supplemental RIBA® and PCR assays as required. The table below summarizes the distribution of OraQuick® HCV Rapid Antibody Test reactive, non-
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 12
16
{12}
reactive, and invalid results in subject with HCV infected status per the reference laboratory testing algorithm.
| OraQuick® HCV Rapid Antibody Test Results | Subject HCV Infected Status | | |
| --- | --- | --- | --- |
| | Positive | Negative | Unable to Determine Infected Status |
| Positive | 435 | 0 | 8 |
| Negative | 1 | 762 | 1 |
| Invalid | 0 | 0 | 0 |
### Percent Positive and Negative Agreement Calculations
Percent positive and percent negative agreement between the OraQuick® HCV Rapid Antibody Test and HCV status were calculated overall for the analysis population (n=1207), as well as for subjects with signs or symptoms of hepatitis and subjects at risk for hepatitis C infection.
Percent Positive Agreement = Number of OraQuick® HCV Rapid Antibody Test Reactive Results x 100
Total number of HCV Infected status
Percent Negative Agreement = Number of OraQuick® HCV Rapid Antibody Test Non-Reactive Results x 100
Total number of HCV Not Infected status
For the purposes of calculating percent agreement, OraQuick® HCV Rapid Antibody Test reactive results for samples whose HCV status was “Unable to Determine” following EIA with supplemental RIBA® and PCR testing were considered “HCV Not Infected”, and OraQuick® HCV Rapid Antibody Test non-reactive results for samples whose HCV status was “Unable to Determine” following EIA with supplemental RIBA® and PCR testing were considered “HCV Infected”.
### Percent Positive and Negative Agreement
The percent positive and negative agreement between the OraQuick® HCV Rapid Antibody Test and the subject HCV Infected Status were calculated for the per protocol population (n=1207). Percent positive and negative agreements were also calculated for individuals with signs or symptoms of hepatitis (n=142), and for individuals at risk for hepatitis C infection (n=1064). Percent positive and negative agreements according to risk factors for HCV infection were also calculated. The risks for HCV were ranked on a clinical evaluation of the likelihood of acquiring hepatitis C, with the most common given higher rankings.³ Each subject was assigned only one risk (the highest). Results with the 95% confidence intervals are summarized in the following table.
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 13
17
{13}
| Study Subjects | Total | Positive Percent Agreement | 95% Exact Confidence Interval | Negative Percent Agreement | 95% Exact Confidence Interval |
| --- | --- | --- | --- | --- | --- |
| Overall | 1207 | 99.5%* (435 / 437) | 98.4, 99.9 | 99.0%* (762 / 770) | 98.0, 99.6 |
| Overall with signs or symptoms | 142 | 100.0% (54 / 54) | 93.4, 100.0 | 100.0% (88 / 88) | 95.9, 100.0 |
| Overall without signs or symptoms | 1064 | 99.5%* (381 / 383) | 98.1, 99.9 | 98.8%* (673 / 681) | 97.7, 99.5 |
| IVDU | 456 | 99.3% (291 / 293) | 97.6, 99.9 | 98.2% (160 / 163) | 94.7, 99.6 |
| Dialysis | 6 | 100% (1 / 1) | 2.5, 100.0 | 100.0% (5 / 5) | 47.8, 100.0 |
| Transfusion/Transplant | 63 | 100.0% (16 / 16) | 79.4, 100.0 | 100.0% (47 / 47) | 92.5, 100.0 |
| High Risk sex | 461 | 100.0% (58 / 58) | 93.8, 100.0 | 98.8 (398 / 403) | 97.1, 99.6 |
| HCV positive mother | 2 | 100.0% (1 / 1) | 2.5, 100.0 | 100.0% (1 / 1) | 2.5, 100.0 |
| Prior history of incarceration | 56 | 100% (11 / 11) | 71.5, 100.0 | 100.0% (45 / 45) | 92.1, 100.0 |
| HIV positive^{§} | 17 | 100.0 (2 / 2) | 15.8, 100.0 | 100.0% 15 / 15 | 78.2, 100.0 |
| None specified | 3 | 100.0% (1 / 1) | 2.5, 100.0 | 100.0% (2 / 2) | 15.8, 100.0 |
*Includes subjects with "unable to determine" status.
§Does not include 377 additional HIV positive subjects enrolled but included in higher ranked risk categories, and 6 HIV positive subjects enrolled with signs or symptoms of hepatitis.
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 14
18
{14}
# RESULTS OF SUPPLEMENTAL TESTING OF SPECIMENS REACTIVE IN THE ORAQUICK® HCV RAPID ANTIBODY TEST
The table below shows the results obtained when subjects reactive in the OraQuick® HCV Rapid Antibody Test were tested by recombinant immunoblot assay (RIBA®).
| Number of OraQuick Reactive Results | RIBA® Results | | |
| --- | --- | --- | --- |
| | Positive | Indeterminate | Negative |
| 443 | 418 | 25* | 0 |
*Seventeen (17) of the RIBA® indeterminate results were positive for HCV RNA when tested by PCR.
Of the subjects reactive in the OraQuick® HCV Rapid Antibody Test 94.4% (418/443) were positive by RIBA®. Seventeen (17) of the RIBA® indeterminate results were positive for HCV RNA when tested by PCR.
# FINGERSTICK WHOLE BLOOD
# Expected Results for the Intended Use Population
Of the 1670 fingerstick whole blood specimens tested in an OraQuick® HCV Rapid Antibody clinical study, 78.7% (1315/1670) were from subjects at risk for hepatitis C infection but were asymptomatic and reported no current signs or symptoms of hepatitis, and 21.3% (355/1670) were from subjects with current signs or symptoms of hepatitis. The 1670 individuals were enrolled from the following collection locations:
29.9% from Ft. Lauderdale, FL
15.2% from Miami, FL
9.8% from Allentown, PA
3.1% from Lebanon, NH
20.5% from New Bedford, MA
12.2% from Lexington, KY
9.3% from Baltimore, MD
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 15
19
{15}
A total of 1660 specimen results were included in the study analysis, as ten (10) OraQuick® results were excluded due to results read outside of the 20-40 minute read window. The OraQuick® HCV Rapid Antibody Test was reactive in 43.5% (722/1660) of subjects. There were no invalid OraQuick® HCV Rapid HCV Antibody Test results reported for the 1670 individuals tested (0% (0/1670) with 95% CI: 0.0% to 0.2%). Of the 1670 individuals tested, 26.6% (445/1670) were also self-reported HIV positive. The table below summarizes the distribution of OraQuick® HCV Rapid Antibody Test reactive, non-reactive, and invalid results for the 1660 subjects included in the analysis.
| Age Range | Gender | OraQuick® HCV Rapid Antibody Test Results in High Risk Individuals – Fingerstick Whole Blood | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | No signs or symptoms | | | | Signs or symptoms | | | |
| | | Reactive | Non-Reactive | Invalid | Total (n) | Reactive | Non-Reactive | Invalid | Total (n) |
| | | n (%) | n (%) | n (%) | | n (%) | n (%) | n (%) | |
| 0-10 | F | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| | M | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| 11-19 | F | 3 (0.2) | 8 (0.6) | 0 (0.0) | 11 | 0 (0.0) | 6 (1.7) | 0 (0.0) | 6 |
| | M | 0 (0.0) | 11 (0.8) | 0 (0.0) | 11 | 1 (0.2) | 2 (0.6) | 0 (0.0) | 3 |
| 20-29 | F | 29 (2.2) | 86 (6.6) | 0 (0.0) | 115 | 9 (2.5) | 11 (3.1) | 0 (0.0) | 20 |
| | M | 25 (1.9) | 73 (5.6) | 0 (0.0) | 98 | 5 (1.4) | 9 (2.5) | 0 (0.0) | 14 |
| 30-39 | F | 31 (2.4) | 65 (5.0) | 0 (0.0) | 96 | 9 (2.5) | 13 (3.7) | 0 (0.0) | 22 |
| | M | 50 (3.8) | 80 (6.1) | 0 (0.0) | 130 | 16 (4.5) | 20 (5.6) | 0 (0.0) | 36 |
| 40-49 | F | 63 (4.8) | 102 (7.8) | 0 (0.0) | 165 | 23 (6.5) | 27 (7.6) | 0 (0.0) | 50 |
| | M | 109 (8.4) | 184 (14.1) | 0 (0.0) | 293 | 46 (13.0) | 28 (7.9) | 0 (0.0) | 74 |
| 50-59 | F | 48 (3.7) | 46 (3.5) | 0 (0.0) | 94 | 18 (5.1) | 13 (3.7) | 0 (0.0) | 31 |
| | M | 134 (10.3) | 106 (8.1) | 0 (0.0) | 240 | 64 (18.0) | 24 (6.8) | 0 (0.0) | 88 |
| 60-69 | F | 8 (0.6) | 4 (0.3) | 0 (0.0) | 12 | 3 (0.8) | 1 (0.3) | 0 (0.0) | 4 |
| | M | 21 (1.6) | 18 (1.4) | 0 (0.0) | 39 | 7 (2.0) | 0 (0.0) | 0 (0.0) | 7 |
| 70-79 | F | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| | M | 0 (0.0) | 1 (0.1) | 0 (0.0) | 1 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| 80-89 | F | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| | M | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| 90-100 | F | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| | M | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 |
| Total (N)* | | 521 (40.0) | 784 (60.0) | 0 (0.0) | 1305 | 201 (56.6) | 154 (43.4) | 0 (0.0) | 355 |
*Excludes 10 subjects with OraQuick results read out of the 20-40 minute read window.
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 16
20
{16}
# Venous Whole Blood Clinical Performance
A multi-center prospective study was conducted to evaluate the clinical performance of the OraQuick® HCV Rapid Antibody Test in fingerstick whole blood specimens from subjects with signs or symptoms of hepatitis and subjects at risk for hepatitis C infection. These risk factors included past or present intravenous drug use, having received a blood transfusion or organ transplant prior to 1992, evidence of high-risk sexual behavior, being born to an HCV positive mother, having been on long-term hemodialysis, history of incarceration, and positive for HIV. Clinical performance was evaluated in fingerstick whole blood specimens from subjects prospectively enrolled at 8 geographically dispersed centers within the United States. The population tested was Caucasian (53.1%), African American (40.6%), as well as a small proportion of other ethnic groups (6.3%). The mean age was 42.8 years (age range: 14 to 77 years). Of the 1660 subject specimens in the analysis population, 719 were HCV infected, 926 were negative, and 15 specimens had the status of "Unable to Determine". HCV status was determined for each subject by EIA, with supplemental RIBA® and PCR assays as required. The table below summarizes the distribution of OraQuick® HCV Rapid Antibody Test reactive, non-reactive, and invalid results in subjects with HCV infected status per the reference laboratory testing algorithm.
| OraQuick® HCV Rapid Antibody Test Results | Subject HCV Infected Status | | |
| --- | --- | --- | --- |
| | Positive | Negative | Unable to Determine Infected Status |
| Positive | 708 | 3 | 11 |
| Negative | 11* | 923 | 4 |
| Invalid | 0 | 0 | 0 |
*Six (6) of the eleven (11) were negative for HCV RNA by PCR.
# Percent Positive and Negative Agreement Calculations
Percent positive and negative agreement between the OraQuick® HCV Rapid Antibody Test and HCV status were calculated overall for the analysis population (n=1660), as well as for subjects with signs or symptoms of hepatitis and subjects at risk for hepatitis C infection.
Percent Positive Agreement = Number of OraQuick® HCV Rapid Antibody Test Reactive Results x 100
Total number of HCV Infected status
Percent Negative Agreement = Number of OraQuick® HCV Rapid Antibody Test Non-Reactive Results x 100
Total number of HCV Not Infected status
For the purposes of calculating percent agreement, subjects reactive by the OraQuick HCV Rapid Antibody Test whose HCV status was "Unable to Determine" were considered "HCV Not Infected" and non-reactive subjects by the OraQuick HCV Rapid Test whose HCV status was "Unable to Determine" were considered "HCV Infected"
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 17
21
{17}
# Percent Positive and Negative Agreement
The percent positive and negative agreement between the OraQuick® HCV Rapid Antibody Test and the subject HCV Infected Status were calculated for the analysis population (n=1660). Percent positive and negative agreement was also calculated for individuals with signs or symptoms of hepatitis, and for individuals at risk for hepatitis C infection. In addition, the percent positive and negative agreements according to risk factors for HCV infection were also calculated. The risks for HCV were ranked on a clinical evaluation of the likelihood of acquiring hepatitis C, with the most common given higher rankings.³ Each subject was assigned only one risk (the highest ranking). Results with the 95% confidence intervals are summarized in the following tables.
Percent Positive Agreement and Percent Negative Agreement According to Risk
| Study Subjects | Total | Percent Positive Agreement | 95% Exact Confidence Interval | Percent Negative Agreement | 95% Exact Confidence Interval |
| --- | --- | --- | --- | --- | --- |
| Overall | 1660 | 97.9%* (708 / 723) | 96.6%, 98.8% | 98.5%* (923 / 937) | 97.5%, 99.2% |
| Overall with signs and symptoms | 355 | 99.0%* (197 / 199) | 96.4%, 99.9% | 97.4%* (152 / 156) | 93.6%, 99.3% |
| Overall without signs or symptoms | 1305 | 97.5%* (511 / 524) | 95.8%, 98.7% | 98.7%* (771 / 781) | 97.7%, 99.4% |
| IVDU^{€} | 661 | 98.2% (428 / 436) | 96.4%, 99.2% | 97.3% (219 / 225) | 94.3%, 99.0% |
| Dialysis | 11 | 100.0% (2 / 2) | 15.8%, 100.0% | 100.0% (9 / 9) | 66.4%, 100.0% |
| Transfusion / Transplant | 48 | 92.3% (12 / 13) | 64.0%, 99.8% | 97.1% (34 / 35) | 85.1%, 99.9% |
| High Risk Sex | 502 | 96.5% (55 / 57) | 87.9%, 99.6% | 99.6% (443 / 445) | 98.4%, 99.9% |
| HCV positive mother | 5 | No subjects met criteria | No subjects met criteria | 100.0% (5 / 5) | 47.8%, 100.0% |
| Prior history of incarceration | 67 | 86.7% (13 / 15) | 59.5%, 98.3% | 98.1% (51 / 52) | 89.7%, 100.0% |
| HIV positive^{§} | 11 | 100.0% (1 / 1) | 2.5%, 100.0% | 100.0% (10 / 10) | 69.2%, 100.0% |
*Includes subjects with "unable to determine" status.
§Does not include 314 additional HIV positive subjects enrolled but included in higher ranked risk categories, and 120 HIV positive subjects enrolled with signs or symptoms of hepatitis.
€Intravenous Drug User
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 18
22
{18}
# Results of Supplemental Testing of Specimens Reactive in the OraQuick® HCV Rapid Antibody Test
The table below shows the results obtained when subjects reactive in the OraQuick® HCV Rapid Antibody Test were tested by recombinant immunoblot assay (RIBA®).
| Number of OraQuick Reactive Results | RIBA® | | |
| --- | --- | --- | --- |
| | Positive | Indeterminate | Negative |
| 722§ | 690 | 29* | 2 |
*Eighteen (18) of the RIBA® indeterminate results were positive for HCV RNA when tested by PCR.
§ One (1) subject reactive by OraQuick did not have RIBA or PCR completed.
Of the subjects reactive in the OraQuick® HCV Rapid Antibody Test 95.6% (690/722) were positive by RIBA®. Eighteen (18) of the RIBA® indeterminate results were positive for HCV RNA when tested by PCR.
# X. PANEL MEETING RECOMMENDATION AND FDA'S POST-PANEL ACTION
In accordance with the provisions of section 515(c)(2) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the Microbiology Panel, an FDA advisory committee, for review and recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel.
# XI. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES
The data from the clinical and non-clinical studies demonstrated acceptable positive and negative percent agreement, seroconversion panel detection, and genotype detection of the OraQuick® HCV Rapid Antibody Test, when used according to the instructions for use in the labeling. The clinical studies in this application indicate that the OraQuick® HCV Rapid Antibody Test is safe and effective when used according to the directions for use in the labeling.
# A. Overall Conclusions
The data in this application support the reasonable assurance of safety and effectiveness of this device when used in accordance with the indications for use.
# XII. CDRH DECISION
CDRH issued an approval order on February 18, 2011. The applicant's manufacturing facilities were inspected and found to be in compliance with the Quality System (QS) Regulation (21 CFR 820).
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 19
23
{19}
### XIII. APPROVAL SPECIFICATIONS
Directions for use: See device labeling.
Hazards to Health from Use of the Device: See Indications, Contraindications, Warnings, Precautions, and Adverse Events in the device labeling.
Post-approval Requirements and Restrictions: See approval order.
### XIV. REFERENCES
1. CDC, Universal Precautions for Prevention of Transmission of Human Immunodeficiency Virus, Hepatitis B Virus, and other Bloodborne Pathogens in Health-Care Settings. MMWR 1988; 37(24):377-388.
2. CDC, Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR 2001; 50 (RR-11):1-42.
3. CDC, Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV – Related Chronic Disease. MMWR 1998; 47(RR19): 1-39.
PMA P080027/S001: FDA Summary of Safety and Effectiveness Data
page 20
24
