GEN-PROBE APTIMA COMBO 2 ASSAY

K032554 · Gen-Probe, Inc. · LSL · Dec 31, 2003 · Microbiology

Device Facts

• Record ID: K032554
• Device Name: GEN-PROBE APTIMA COMBO 2 ASSAY
• Applicant: Gen-Probe, Inc.
• Product Code: LSL · Microbiology
• Decision Date: Dec 31, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3390
• Device Class: Class 2

Intended Use

The APTIMA Combo 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal ribonucleic acid (rRNA) from Chlamydia trachomatis and/or Neisseria gonorrhoeae in clinician-collected endocervical, vaginal, and male urethral swab specimens, patient-collected vaginal swab specimens* and male and female urine specimens. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease. *Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use. The APTIMA Vaginal Swab Specimen Collection Kit is for use with the APTIMA Assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The APTIMA Vaginal Swab Specimen Collection Kit is intended to be used for clinician and patient collection of vaginal swab specimens according to the instructions provided. Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The APTIMA Vaginal Swab Specimen Collection Kit is not for home use.

Device Story

The APTIMA Combo 2 Assay is an in vitro diagnostic test for detecting Chlamydia trachomatis and Neisseria gonorrhoeae rRNA. The system uses target capture, nucleic acid amplification, and hybridization with acridinium ester-labeled DNA probes. The ancillary Vaginal Swab Specimen Collection Kit provides a sterile swab and transport tube with media for collecting vaginal specimens in medical settings. The assay is performed in a laboratory environment. Healthcare providers use the qualitative results to aid in diagnosing urogenital infections. By enabling patient-collected vaginal swabs, the device increases screening options for women when pelvic exams are not indicated, facilitating earlier diagnosis and treatment.

Clinical Evidence

Multi-center clinical study of 1,464 symptomatic and asymptomatic female subjects. Performance evaluated against a patient infected status algorithm based on reference NAAT results from endocervical swabs and urine. Overall sensitivity for C. trachomatis was 96.6% (patient-collected) and 96.7% (clinician-collected); specificity was 97.8% and 97.1%, respectively. For N. gonorrhoeae, sensitivity was 98.7% (patient-collected) and 96.2% (clinician-collected); specificity was 99.6% and 99.4%, respectively.

Technological Characteristics

Target capture and transcription-mediated amplification (TMA). Detection via chemiluminescent acridium ester-labeled probes. Instrumentation: luminometer. Software: dual kinetic assay (DKA) algorithm. Specimen collection: sterile swab with softer bud than unisex swab; transport tube identical to K003395. Qualitative detection of 23S rRNA (C. trachomatis) and 16S rRNA (N. gonorrhoeae).

Indications for Use

Indicated for symptomatic and asymptomatic individuals, including women for screening via patient- or clinician-collected vaginal swabs when a pelvic exam is not otherwise indicated. Not for home use.

Regulatory Classification

Identification

Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identify Neisseria spp. from cultured isolates. Additionally, some of these reagents consist of Neisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence of Neisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Neisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.

Predicate Devices

• Aptima Combo 2 Assay (K003395)
• PACE2 collection (K881277)

Submission Summary (Full Text)

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Summary of Safety and Effectiveness K032554

# DEC 3 1 2003

#### 2. SUMMARY OF SAFETY AND EFFECTIVENESS

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________

Gen-Probe Incorporated

Confidential

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#### GEN-PROBE® APTIMA® Combo 2 Assay GEN-PROBE® APTIMA® Vaginal Swab Specimen Collection Kit

# Sponsor/Contact Information

Submitted By: Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, California 92121 [phone] [phone] (FAX)

Company Contact: Alan Maderazo, Ph.D., RAC Regulatory Affairs Specialist [phone] [phone](FAX) [e-mail]

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Summary of Safety and Effectiveness K032554

## General Information

| Trade Name: | GEN-PROBE® APTIMA® Combo 2 Assay |
|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common or Usual Name: | Ribosomal RNA (rRNA) target-amplified nucleic acid probe<br>test for the <i>in vitro</i> diagnostic detection of <i>Chlamydia</i><br><i>trachomatis</i> and/or <i>Neisseria gonorrhoeae</i> |
| Classification Names: | DNA Probe, Nucleic Acid Amplification, <i>Chlamydia</i><br>DNA Reagents, <i>Neisseria</i> |

# APTIMA Combo 2 Assay

| Device Description | DNA Probe, Nucleic Acid Amplification, Chlamydi |
|--------------------|-------------------------------------------------|
| Medical Specialty | Microbiology |
| Product Code | MKZ |
| Device Class | 1 |
| Regulation number | 866.3120 |

| Device Description | DNA Reagents, Neisseria |
|--------------------|-------------------------|
| Medical Specialty | Microbiology |
| Product Code | LSL |
| Device Class | 2 |
| Regulation number | 866.3390 |

# Substantially Equivalent Devices:

APTIMA Combo 2 Assay; K003395

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#### Device Description

Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Combo 2 Assay to include clinician-collected and patient-collected vaginal swabs (in a medical setting) as acceptable testing specimens. The ancillary kit formulated for this specific application is the GEN-PROBE APTIMA Vaginal Swab Specimen Collection Kit. The components of the APTIMA Vaginal Swab Specimen Collection Kit include: (1) a sterile swab for the collection of vaginal specimens and (2) a transport tube containing transport media with a penetrable cap.

The APTIMA Vaginal Swab Specimen Collection Kit is for use with the APTIMA Assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The APTIMA Vaginal Swab Specimen Collection Kit is intended to be used for clinician and patient collection of vaginal swab specimens according to the instructions provided. The APTIMA Vaginal Swab Specimen Collection Kit not for home use.

The background information describing the relevant diseases, Chilamydia trachomatis and Neisseria gonorrhoeae, and the principles of the APTIMA Combo 2 Assay are provided in the Summary of Safety and Effectiveness for the APTIMA Combo 2 Assay (K003395)

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#### Intended Use

#### AC2 Assay package insert:

The APTIMA Combo 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal ribonucleic acid (rRNA) from Chlamydia trachomatis and/or Neisseria gonorrhoeae in clinician-collected endocervical, vaginal, and male urethral swab specimens, patient-collected vaginal swab specimens* and male and female urine specimens. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease.

*Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use.

#### Ancillary Kit package insert:

The APTIMA Vaginal Swab Specimen Collection Kit is for use with the APTIMA Assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The APTIMA Vaginal Swab Specimen Collection Kit is intended to be used for clinician and patient collection of vaginal swab specimens according to the instructions provided. Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The APTIMA Vaginal Swab Specimen Collection Kit is not for home use.

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## Summary of Technological Characteristics of the APTIMA Combo 2 Assay

The APTIMA Combo 2 Assay incorporates the technologies of target capture, in vitro nucleic acid amplification, and hybridization of target amplicons with acridinium ester-labeled DNA probes to specifically detect and differentiate both C. trachomatis and N. gonorrhoeae nucleic acids in clinical specimens. GEN-PROBE's proprietary technologies are combined in this product to allow qualitative detection of C. trachomatis rRNA and N. gonorrhoeae rRNA.

#### Analytical Sensitivity

Chlamydia trachomatis analytical sensitivity (limits of detection) was determined by directly comparing dilutions of C. trachomatis organisms in cell culture and in the assay. The analytical sensitivity claim for the assay is one Inclusion-Forming Unit (IFU) per assay (7.25 IFU/swab, 5 IFU/mL urine) for all 15 C. trachomatis serovars. However, dilutions of less than one IFU/assay of all serovars tested positive in the APTIMA Combo 2 Assay.

Neisseria gonorrhoeae analytical sensitivity was determined by directly comparing dilutions of 57 different clinical isolates in culture and in the APTIMA Combo 2 Assay. The analytical sensitivity claim for the assay is 50 cells/assay (362 cells/swab, 250 cells/mL urine). However, all strains tested were positive at less than 50 cells/assay.

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## Analytical Specificity

A total of 154 culture isolates were evaluated using the APTIMA Combo 2 Assay. These isolates included 86 organisms that may be isolated from the urogenital tract and 68 additional organisms that represent a phylogenetic cross-section of organisms. The tested organisms included bacteria, fungi, yeast, parasites, and viruses. All organisms except C. psittaci, C. pneumoniae, and the viruses were tested at 1.0x106 cells/assay in both swab and urine transport medium. C. psittaci and C. pneumoniae were tested at 1.0x10 TFU/assay. The viruses were tested as follows: (a) herpes simplex viruses I and II: 6.0x104 TCID50/assay, (b) human papilloma virus 16: 2.9x106 DNA copies/assay and (c) cytomegalovirus: 1x106 infected cell culture cells/assay. Only C. trachomatis and N. gonorrhoeae samples produced positive results in the APTIMA Combo 2 Assay. The list of organisms tested is shown in the following table.

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## Analytical Specificity

| ORGANISM | ORGANISM | ORGANISM |
|------------------------------|---------------------------------|-------------------------------|
| Achromobacter xerosis | Escherichia coli | Neisseria mucosa (3) |
| Acinetobacter calcoaceticus | Flavobacterium meningosepticum | Neisseria sicca (3) |
| Acinetobacter Iwoffi | Fusobacterium nucleatum | Neisseria subflava (14) |
| Actinomyces israelii | Gardnerella vaginalis | Neisseria perflava |
| Actinomyces pyogenes | Gemella haemolysans | Neisseria polysaccharea |
| Aerococcus viridans | Haemophilus ducreyi | Paracoccus denitrificans |
| Aeromonas hydrophila | Haemophilus influenzae | Peptostreptococcus anaerobius |
| Agrobacterium radiobacter | Herpes simplex virus I | Peptostreptococcus productus |
| Alcaligenes faecalis | Herpes simplex virus II | Plesiomonas shigelloides |
| Bacillus subtilis | Human papilloma virus 16 | Propionibacterium acnes |
| Bacteriodes fragilis | Kingella dentrificans | Proteus mirabilis |
| Bacteriodes ureolyticus | Kingella kingae | Proteus vulgaris |
| Bifidobacterium adolescentis | Klebsiella oxytoca | Providencia stuartii |
| Bifidobacterium brevi | Klebsiella pneumoniae | Pseudomonas aeruginosa |
| Branhamella catarrhalis | Lactobacillus acidophilus | Pseudomonas fluorescens |
| Brevibacterium linens | Lactobacillus brevis | Pseudomonas putida |
| Campylobacter jejuni | Lactobacillus jensonii | Rahnella aquatilis |
| Candida albicans | Lactobacillus lactis | Rhodospirillum rubrum |
| Candida glabrata | Legionella pneumophila (2) | Saccharomyces cerevisiae |
| Candida parapsilosis | Leuconostoc paramensenteroides | Salmonella minnesota |
| Candida tropicalis | Listeria monocytogenes | Salmonella typhimurium |
| Chlamydia pneumoniae | Micrococcus luteus | Serratia marcescens |
| Chlamydia psittaci (2) | Moraxella lacunata | Staphylococcus saprophyticus |
| Chromobacterium violaceum | Moraxella osloensis | Staphylococcus aureus |
| Citrobacter freundii | Morganella morganii | Staphylococcus epidermidis |
| Clostridium perfringens | Mycobacterium smegmatis | Streptococcus agalactiae |
| Corynebacterium genitalium | Mycoplasma genitalium | Streptococcus bovis |
| Corynebacterium xerosis | Mycoplasma hominis | Streptococcus mitis |
| Cryptococcus neoformans | N. meningitidis Serogroup A | Streptococcus mutans |
| Cytomegalovirus | N. meningitidis Serogroup B | Streptococcus pneumoniae |
| Deinococcus radiodurans | N. meningitidis Serogroup C (4) | Streptococcus pyogenes |
| Derxia gummosa | N. meningitidis Serogroup D | Streptococcus salivarius |
| Eikenella corrodens | N. meningitidis Serogroup Y | Streptococcus sanguis |
| Enterobacter aerogenes | N. meningitidis Serogroup W135 | Streptococcus griseinus |
| Enterobacter cloacae | Neisseria cinerea (4) | Trichomonas vaginalis |
| Enterococcus avium | Neisseria dentrificans | Ureaplasma urealyticum |
| Enterococcus faecalis | Neisseria elongata (3) | Vibrio parahaemolyticus |
| Enterococcus faecium | Neisseria flava | Yersinia enterocolitica |
| Erwinia herbicola | Neisseria flavescens (2) | |
| Erysipelothrix rhusiopathiae | Neisseria lactamica (9) | |

(n) = number of strains tested

(1) - hamber or earline tested in the APTIMA Combo 2 Assay based on kinetic profile type and RLU.

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## Interference Studies

The following table lists the commonly encountered substances found in vaginal swab specimens that were tested in the assay. All were tested for potential assay interference in the absence and presence of C. trachomatis and N. gonorrhoeae at the estimated rRNA equivalent of one C. trachomatis IFU/assay (5 fg/assay) and 50 N. gonorrhoeae cells/assay (250 fg/assay). The rRNA equivalents were calculated based on the genome size and estimated DNA:RNA ratio/cell of each organism.

| Swab | Urine |
|-------------------------------|-------------------------------|
| 10% Blood | 30% Blood |
| Contraceptive jelly | Urine analytes: |
| Spermicide | Protein |
| Moisturizer | Glucose |
| Hemorrhoidal anesthetic | Ketones |
| Body oil | Bilirubin |
| Powder | Nitrate |
| Anti-fungal cream | Urobilinogen |
| Vaginal lubricants | pH 4 (acidic) |
| Feminine spray | pH 9 (alkaline) |
| Leukocytes (1 x 106 cells/mL) | Leukocytes (1 x 106 cells/mL) |
| | Cellular debris |
| | Vitamins |
| | Minerals |
| | Acetaminophen |
| | Aspirin |
| | Ibuprofen |

## Interfering Substances Testing

No interference was observed with any of the tested substances.

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#### Recovery

Lactobacillus acidophilus, Gardnerella vaginalis, Bacteroides ureolyticus and Staphylococcus epidermidis (1 x 108 cells/assay) were added to pooled negative vaginal swab samples containing the rRNA equivalent of approximately one C. trachomatis IFU (5 fg) and 50 N. gonorrhoeae cells (250 fg). These additions did not interfere with the amplification and detection of C. trachomatis or N. gonorrhoeae rRNA using the APTIMA Combo 2 Assay.

#### Vaginal Swab Specimen Clinical Study Results

In the vaginal swab specimen multi-center clinical study, 1,464 symptomatic and asymptomatic female subjects attending STD, OB/GYN, teen, and family planning clinics were enrolled into the clinical study. Subjects were classified as symptomatic if symptoms such as discharge, dysuria, and pelvic pain were reported by the subjects were classified as asymptomatic if the subject did not report symptoms. Of the 646 asymptomatic subjects enrolled in the study, two were less than 16 years of age, 158 were between the ages of 16 and 20, 231 were between the ages of 21 and 25, and 255 were greater than 25 years of age. Of the 818 symptomatic subjects enrolled in the study, 160 were between the ages of 16 and 20, 324 were between the ages of 21 and 25, and 334 were greater than 25 years of age.

Five specimens were collected from each eligible subject; one urine specimen, one patientcollected vaginal swab, one clinician-collected vaginal swab, and two randomized endocervical swabs. APTIMA Combo 2 Assay results were generated from the two vaginal swabs, one of the endocervical swabs, and an aliguot of the urine specimen. The second endocervical swab and a second aliquot of the urine specimen were tested using another commercially-available nucleic acid amplification test (NAAT) for C. trachomatis and another commercially-available NAAT for N. gonorrhoeae. Endocervical swab and urine specimens tested in the APTIMA Combo 2 Assay and the other commercially available NAATs were used as reference NAATs to determine infected status for each subject in the vaginal swab specimen clinical study.

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Specimen testing was conducted either at the site of subject enrollment or at an external testing site.

All performance calculations were based on the total number of APTIMA Combo 2 Assay patient- and clinician-collected vaginal swab results compared to a patient infected status algorithm. A total of 2,868 C. trachomatis and 2,867 N. gonorrhoeae vaginal swab test results were used in the data analysis. In the algorithm, the designation of a subject as being infected or not infected with C. trachomatis or N. gonorrhoeae was based on endocervical swab and urine specimen results from the commercially-available APTIMA Combo 2 Assay and the other commercially-available NAAT. Subjects were considered infected with C. trachomatis or N. gonorrhoeae if two of the four endocervical swab and urine specimens tested positive in the APTIMA Combo 2 Assay and the other reference NAAT (one specimen testing positive in each NAAT). Subjects were considered non-infected if less than two reference NAAT results were positive. Tables 1 and 2 summarize the number of results from symptornatic and asymptomatic subjects designated as infected or non-infected with C. trachomatis or N. gonorrhoeae, respectively, according to the patient infected status algorithm. For this clinical study, two commercially available NAATs were used to determine GC-infected status. Culture was not used as a reference test since the APTIMA Combo 2 Assay has already been evaluated against culture for other specimen types (refer to K003395).

Sensitivity and specificity for C. trachomatis by gender, specimen type and symptom status are presented in Table 3. Table 4 shows the APTIMA Combo 2 Assay sensitivity, specificity, and predictive values for C. trachomatis compared to patient infected status for each clinical site and overall. Sensitivity and specificity for detection of N. gonorrhoeae by gender, specimen type and symptom status are presented in Table 5. Table 6 shows the N. gonorrhoeae sensitivity, specificity, and predictive values for the APTIMA Combo 2 Assay compared to patient infected status for each clinical site and overall. Samples that were APTIMA Combo 2 Assay positive and infected patient status negative (i.e., apparent false positives) were tested in alternate TMA assays for C. trachomatis and N. gonorrhoeae that targeted sequences unique

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from those targeted in APTIMA Combo 2. The results of the alternate TMA assays were not used to change the original patient categorizations (Tables 3 and 5).

Of the 1,464 subjects enrolled, there were 13 subjects with unknown CT patient infected status and 14 subjects with unknown GC patient infected status. Subjects were designated with an unknown patient infected status if results were missing that prevented conclusive determination of infected status. These subjects' results were not included in any performance calculations. Of the 5,782 APTIMA Combo 2 Assay vaginal swab results from the multi-center clinical study, there was a small percentage (28, 0.5%) of vaginal swab specimens that initially tested invalid or equivocal for CT or GC. Upon repeat testing only three C. trachomatis results and two N. gonorrhoeae results were equivocal and were excluded from the analysis. No specimens tested invalid on repeat testing.

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| Effectiveness<br>and<br>Safety<br>of | |
|--------------------------------------|---------|
| .mary | K032554 |
| r | |

| NAAT 1 | | NAAT 2 (APTIMA Combo 2 Assay) | | APTIMA Combo 2 Assay | | Symptom Status | | Total | |
|-------------------------|-------------------|-------------------------------|--------------------------------|----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------|-------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|
| Patient Infected Status | Endocervical Swab | Urine | Endocervical Swab | Urine | Patient-Collected Vaginal Swab | Clinician-Collected Vaginal Swab | Symptomatic | Asymptomatic | |
| Infected | + | + | + | + | + | + | 79 | 43 | 122 |
| Infected | + | + | + | + | + | + | 0 | 1 | 1 |
| Infected | + | + | + | + | N/A | + | 8 | 5 | 13 |
| Infected | + | + | + | - | N/A | + | 1 | 0 | 1 |
| Infected | + | + | + | = | + | + | 1 | 0 | 1 |
| Infected | + | + | + | + | + | + | 8 | 3 | 11 |
| Infected | + | + | + | + | + | + | 1 | 2 | 3 |
| Infected | + | + | + | N/A | + | + | 1 | 0 | 1 |
| Infected | + | + | + | + | + | + | 5 | 3 | 8 |
| Infected | + | + | + | + | + | + | 5 | 0 | 5 |
| Infected | + | + | + | + | + | + | 2 | 0 | 2 |
| Infected | + | + | + | + | + | + | 1 | 4 | 5 |
| Non-infected | - | - | - | - | - | - | 0 | 1 | 1 |
| Non-infected | - | - | - | - | - | - | 0 | 4 | 4 |
| Non-infected | - | - | - | - | - | - | 2 | 1 | 3 |
| Non-infected | - | - | - | - | N/A | - | 6 | 4 | 10 |
| Non-infected | - | + | - | + | - | + | 1 | 0 | 1 |
| Non-infected | - | + | - | + | - | + | 4 | 2 | 6 |
| Non-infected | - | + | - | + | - | + | 1 | 0 | 1 |
| Non-infected | - | + | - | + | - | + | 2 | 0 | 2 |
| Non-infected | - | + | - | + | - | + | 1 | 2 | 3 |
| Non-infected | - | + | - | + | - | + | 2 | 3 | 5 |
| | NAAT | | T 2 (APTIMA Combo Assay)<br>NA | | | PTIMA Combo 2 Assa | | /mptom Stat | |
| tient Infecte Status | ndocervic<br>Swab | Urine | Endocervica<br>Swab | Urine | Patient- Collected Iginal Swa | Clinician- Collected Taginal Swa | mptomatic | Asymptomat | Госа |
| | | | | | -+- | | | | |
| | l | | | | | + | ਟਾ ਕੇ ਉੱ | ದ ೧೯೭೪ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧ | ារ ប្រជាជនជាតិ ។ ស |
| | - | - | | - | ) | | | | |
| | | | | - | - | N/A | 0 | | |
| | | - | | 1 | | に | | | |
| | 1 | - | | - | | + | 0 | | |
| | l | - | 1 | l | | l | । | 8 | 61 |
| | - | - | - | - | る。 そのため、その他 その他の あなたのです。 その他の人気がない ないかなかなかなかなかったのです。 その他の人気がないということです。 その他の人気がない。 その他の人気がない。 その他の人気がない。 その他の人気がない。 その他の人気がない。 その他の人気がない。 その他の人気がない。 その他の人気がない。 その他の人気がない。 その他 | N/A | I | 0 | |
| | - | | l | 1 | | ll | | l | |
| | l | l | 1 | | == | + | | | |
| | l | | - | 1 | - | | | নে | P |
| | - | VIN VIN | 1 | - | N/A | - | 00 NO Do | | |
| | l | ll | - | l | l | | | 6 | N |
| | - | | - | - | - | N/A | | | |
| | = | - | l | - | 1 | | 【 | | ਨ |
| | | t | l | N/A | - | l | 0 ທ | | |
| | * | - | N/A | l | - | - | | p | 6 |
| | | - | ll | | | + | | | |
| | | | ll | | | | | | |
| Total | | | | | | | 811 | હ્વા | ્વર્સ |
| | | | | | | | | | |

able 1: C. trachomatis Patient- and Clinician-Collected Vaginal Swab Specimen Analysis for Female Patient Infected Statu

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. . .mary of Safety and Effectivene
K032554

N/A = Specimen not obtained or available for testing
= represents equivocal on repeat testing

- Represents equivalent on repeat testing

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| Summary of Safety and Effectiveness |
|-------------------------------------|
| K032554 |

| Patient Infected<br>Status | NAAT 1 | | NAAT 2 (APTIMA Combo 2 Assay) | | | APTIMA Combo 2 Assay | | | Symptom Status | | Total |
|----------------------------|----------------------|-------|-------------------------------|-------|---------------------------------------|-----------------------------------------|-------------|--------------|----------------|--|-------|
| | Endocervical<br>Swab | Urine | Endocervical<br>Swab | Urine | Patient-<br>Collected<br>Vaginal Swab | Clinician-<br>Collected<br>Vaginal Swab | Symptomatic | Asymptomatic | | | |
| Infected | + | + | + | + | + | + | 44 | 15 | 59 | | |
| Infected | + | + | + | + | + | + | 1 | 0 | 1 | | |
| Infected | + | + | + | + | N/A | + | 0 | 1 | 1 | | |
| Infected | + | + | + | + | + | + | 1 | 0 | 1 | | |
| Infected | + | + | + | + | + | + | 2 | 2 | 4 | | |
| Infected | + | + | + | + | + | + | 1 | 1 | 2 | | |
| Infected | + | + | + | + | + | + | 1 | 1 | 2 | | |
| Infected | + | + | + | + | + | + | 0 | 1 | 1 | | |
| Infected | + | + | + | + | + | + | 1 | 0 | 1 | | |
| Infected | + | + | + | + | + | + | 5 | 1 | 6 | | |
| Non-infected | + | - | + | - | + | + | 1 | 0 | 1 | | |
| Non-infected | + | + | + | + | + | + | 5 | 2 | 7 | | |
| Non-infected | + | + | + | + | + | + | 0 | 1 | 1 | | |
| Non-infected | + | + | + | + | + | + | 2 | 1 | 3 | | |
| Non-infected | + | + | + | + | + | + | 2 | 0 | 2 | | |
| Non-infected | + | + | + | + | + | + | 2 | 2 | 4 | | |
| Non-infected | - | - | - | - | - | - | 698 | 577 | 1275 | | |
| Non-infected | + | N/A | + | N/A | N/A | = | 0 | 2 | 2 | | |
| Non-infected | + | N/A | + | N/A | N/A | N/A | 15 | 9 | 24 | | |
| Non-infected | + | N/A | + | N/A | N/A | N/A | 1 | 0 | 1 | | |
| Non-infected | + | N/A | + | N/A | N/A | N/A | 2 | 2 | 4 | | |
| Non-infected | + | N/A | + | N/A | N/A | N/A | 11 | 10 | 21 | | |

Table 2: N. gonorrhoeae Patient- and Clinician-Collected Vaginal Swab Specimen Analysis for Female Patient Infected Statu

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mary of Safety and Effectivenes ﺮ ﺍﻟﻤﺮﺍﺟﻊ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍ

| 2554 |
|------|
| |
| |
| |
| 03 |
| |
| ਮ |

| Patient Infected<br>Status | NAAT 1 | | NAAT 2 (APTIMA Combo 2 Assay) | | | APTIMA Combo 2 Assay | | Symptom Status | | Total |
|----------------------------|----------------------|-------|-------------------------------|-------|---------------------------------------|-----------------------------------------|-----------------|------------------|------|-------|
| | Endocervical<br>Swab | Urine | Endocervical<br>Swab | Urine | Patient-<br>Collected<br>Vaginal Swab | Clinician-<br>Collected<br>Vaginal Swab | Symptomati<br>c | Asymptomati<br>c | | |
| Non-infected | - | = | - | - | - | N/A | 0 | 1 | 1 | |
| Non-infected | = | - | - | - | - | - | 1 | 1 | 2 | |
| Non-infected | - | - | N/A | - | - | - | 0 | 1 | 1 | |
| Non-infected | - | - | - | - | - | N/A | 5 | 4 | 9 | |
| Non-infected | - | - | = | - | - | - | 1 | 1 | 2 | |
| Total | | | | | | | 810 | 640 | 1450 | |

N/A = Specimen not obtained or available for testing
= represents equivocal on repeat testing

PERSPECTIVES ON
ISSUES IN INTEGRATED
STUDIES

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| Summary of Safety and Effectiveness |
|-------------------------------------|
| K032554 |

| Specimer | Symptom Status | | TD | FP | TN | FN | | Sensiti vity (95% C.I. | Specificity | (95% C.I |
|-----------------------------------------------------------------------------|----------------|------|-----|------|-------|----|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------|-------------|-------------------------------------------|
| Patient-Collected Vaginal Swat | Asymptomatic | 288 | રહ | । ୧. | રવેવ | | 08:4 | 91.5 - 100 (92.8 - 98.8 | 97.2 | (95.4 - 98.4) |
| | All | 423 | 172 | 28b | 217 | 9 | 96.6 | | 97.8 | 96.8 - 98.5) |
| inician-Collected Vaginal Swab | Symptomatic | 800 | 113 | 23° | રવેત | P | તે છે. 6 | | 96.7 | (95.1 - 97.9) (96.0 - 98.7) (96.0 - 97.9) |
| | Asymptomatic | ર 36 | 61 | l Ag | ર રતે | C | તેરૂ જિલ્લામાં આવેલું એક ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે | 91.5 - 99.1 189.0 - 99.6 192.9 - 98.8 | 97.6 | |
| | | 1445 | | 37° | 228 | | 96.7 | | 97 l | |
| CT TMA Alternate Amplification results: # positive results/# specimens test | | | | | | | | | | |
| a: 13/16 b: 24/28 c: 15/23 d: 13/14 e: 28/37 | | | | | | | | | | |

ble 3: C. trachomatis Sensitivity and Specificity: APTIMA Combo 2 Assay Vaginal Swab Specimens vs. Patient Infected Statu

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:

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| and Effectiveness | |
|-------------------|---------|
| | |
| Safety<br>of | |
| .lary<br>SL. | K032554 |
| | |

| | Table 4: C. trachomatis Performance by Clinical Site: APTIMA Combo 2 Assay Vaginal Swab Specimens vs. Patient Infected Status | | | | | | | | | | | |
|-------------------------------------|-------------------------------------------------------------------------------------------------------------------------------|------|-----|----|------|----|----------|------------------------|------------------------|---------|---------|--|
| Specimen | Site | N | TP | FP | TN | FN | Prev (%) | Sensitivity (95% C.I.) | Specificity (95% C.I.) | PPV (%) | NPV (%) | |
| Patient-Collected<br>Vaginal Swab | 1 | 218 | 34 | 6 | 177 | 1 | 16.1 | 97.1 (85.1 - 99.9) | 96.7 (93.0 - 98.8) | 85.0 | 99.4 | |
| | 2 | 195 | 50 | 6 | 137 | 2 | 26.7 | 96.2 (86.8 - 99.5) | 95.8 (91.1 - 98.4) | 89.3 | 98.6 | |
| | 3 | 111 | 10 | 1 | 100 | 0 | 9.0 | 100 (69.2 - 100) | 99.0 (94.6 - 100) | 90.9 | 100 | |
| | 4 | 261 | 20 | 4 | 236 | 1 | 8.0 | 95.2 (76.2 - 99.9) | 98.3 (95.8 - 99.5) | 83.3 | 99.6 | |
| | 5 | 199 | 13 | 3 | 183 | 0 | 6.5 | 100 (75.3 - 100) | 98.4 (95.4 - 99.7) | 81.3 | 100 | |
| | 6 | 290 | 32 | 5 | 251 | 2 | 11.7 | 94.1 (80.3 - 99.3) | 98.0 (95.5 - 99.4) | 86.5 | 99.2 | |
| | 7 | 102 | 10 | 2 | 90 | 0 | 9.8 | 100 (69.2 - 100) | 97.8 (92.4 - 99.7) | 83.3 | 100 | |
| | 8 | 47 | 3 | 1 | 43 | 0 | 6.4 | 100 (29.2 - 100) | 97.7 (88.0 - 99.9) | 75.0 | 100 | |
| | ALL | 1423 | 172 | 28 | 1217 | 6 | 12.5 | 96.6 (92.8 - 98.8) | 97.8 (96.8 - 98.5) | 86.0 | 99.5 | |
| Clinician-Collected<br>Vaginal Swab | 1 | 227 | 35 | 8 | 182 | 2 | 16.3 | 94.6 (81.8 - 99.3) | 95.8 (91.9 - 98.2) | 81.4 | 98.9 | |
| | 2 | 196 | 50 | 5 | 139 | 2 | 26.5 | 96.2 (86.8 - 99.5) | 96.5 (92.1 - 98.9) | 90.9 | 98.6 | |
| | 3 | 113 | 10 | 2 | 101 | 0 | 8.8 | 100 (69.2 - 100) | 98.1 (93.2 - 99.8) | 83.3 | 100 | |
| | 4 | 262 | 20 | 10 | 231 | 1 | 8.0 | 95.2 (76.2 - 99.9) | 95.9 (92.5 - 98.0) | 66.7 | 99.6 | |
| | 5 | 199 | 13 | 2 | 184 | 0 | 6.5 | 100 (75.3 - 100) | 98.9 (96.2 - 99.9) | 86.7 | 100 | |
| | 6 | 296 | 34 | 8 | 254 | 0 | 11.5 | 100 (89.7 - 100) | 96.9 (94.1 - 98.7) | 81.0 | 100 | |
| | 7 | 102 | 9 | 1 | 91 | 1 | 9.8 | 90.0 (55.5 - 99.7) | 98.9 (94.1 - 100) | 90.0 | 98.9 | |
| | 8 | 50 | 3 | 1 | 46 | 0 | 6.0 | 100 (29.2 - 100) | 97.9 (88.7 - 99.9) | 75.0 | 100 | |
| | ALL | 1445 | 174 | 37 | 1228 | 6 | 12.5 | 96.7 (92.9 - 98.8) | 97.1 (96.0 - 97.9) | 82.5 | 99.5 | |

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18

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| Status |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| - |
| |
| |
| Property |
| |
| |
| |
| 1 |
| 1 |
| Vaginal Swab Specimens vs. Patient Infected Status<br>------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
| a at 10 alle the la |
| 1 1993 1 |
| ombe |
| - |
| DITTS |
| |
| necificity: |
| 1 |
| MITS UNIVERSITY CAS CALLERY CAR CALTACA WA |
| |
| Ancitivity and |
| |
| ver<br>- |
| Onom<br>044<br>. |
| able 5: N. g |
| |
| |
| C |

| and and and and and the commend of the commend of the commend of the comments of the first and the mail of the first and the first and the former the former the forme the for | | | | | | | | | | | |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------|-----|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------|------|----|-------------|----------------------|------------|----------------|--|
| Specimer | Symptom Status | N | 1 L<br>TT | FP | TN | FN | Sensitivity | 95% C.I. | specificit | 95% C.I. | |
| Patient-Collected Vaginal Swab | Asymptomatic | 659 | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------<br>22 | くな<br>খ | ୧୦ર | | 100 | 100<br>84.6 - | 99.7 | 100<br>198.8 - | |
| | All | 423 | 76 | ep | 340 | | 98.7 | 100<br>93.0 - | 99.6 | 99.0 - 99.8 | |
| 'linician-Collected Vaginal Swab Symptomatic | | 807 | ਟ ਤੇ | ર્દ ૮ | 747 | 1 | 96.4 | તેત્વે છ<br>87.5 - . | 99.3 | 98.5 - 99.8) | |
| | Asymptomatic | 637 | 22 | p & | QII | | વેરે 7 | 78.1 - 99.9, | વેત્તે રે | 98.6 - 99.9 | |
| | Al | 444 | 75 | 8 | .358 | | 96.2 | 89.2 - 99.2 | 99.4 | 98.8 - 99.7 | |
| (1) Marte Alexanda Amerificantian maultar # manimano rach | | | | | | | | | | | |

'GC TMA Alternate Amplification results: # positive results/# specimens tested
a: 2/2 b: 6/6 c: 5/5 d: 2/3 e: 7/8

28.66.55.22.33.7

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able 6: N. gonorrhoeae Performance by Clinical Site: APTIMA Combo 2 Assay Vaginal Swab Specimens vs. Patient Infected Stati

| Specime | Site | N | TP | FP | TN | FN | Prev (%) | Sensitivity | (95% C.I.) | Specificity | (95% C.I.) | PPV | NPV |
|----------------------------|-------|---------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------…