(134 days)
No
The device description focuses on nucleic acid amplification and hybridization technologies for qualitative detection, with no mention of AI or ML. The performance studies describe standard clinical trial methodologies and statistical metrics (sensitivity, specificity, etc.), not AI/ML model evaluation.
No.
The device is for in vitro qualitative detection and differentiation of specific rRNA to aid in diagnosis, not for treating or preventing a disease or condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay is for "qualitative detection and differentiation" of specific RRNA to "aid in the diagnosis of gonococcal and/or chlamydial urogenital disease." This direct reference to aiding in diagnosis makes it a diagnostic device.
No
The device description explicitly mentions physical components like a sterile swab and a transport tube containing transport media, which are hardware components. The assay itself is a laboratory test utilizing chemical and biological processes, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the APTIMA Combo 2 Assay is an "in vitro qualitative detection and differentiation" test. This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
- Device Description: The description details a test that analyzes biological specimens (swabs and urine) outside of the body to detect specific nucleic acids (rRNA from Chlamydia trachomatis and Neisseria gonorrhoeae). This is a core function of an IVD.
- Clinical Context: The assay is used "to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease," which is a diagnostic purpose.
- Specimen Types: The device is designed to test various human specimens (endocervical, vaginal, male urethral swabs, and urine).
The APTIMA Vaginal Swab Specimen Collection Kit is an ancillary device used in conjunction with the APTIMA Combo 2 Assay for the collection of specimens, which are then used in the in vitro diagnostic test. Therefore, both components are part of an IVD system.
N/A
Intended Use / Indications for 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.
Product codes (comma separated list FDA assigned to the subject device)
MKZ, LSL
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)
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Urogenital
Indicated Patient Age Range
The study subjects included individuals: two less than 16 years of age, 158 between 16 and 20, 231 between 21 and 25, and 255 greater than 25 in the asymptomatic group. For the symptomatic group: 160 were between 16 and 20, 324 between 21 and 25, and 334 greater than 25.
Intended User / Care Setting
Clinician-collected, patient-collected vaginal swabs (in a medical setting). Not for home use.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Sample Size: 1,464 symptomatic and asymptomatic female subjects were enrolled. A total of 2,868 C. trachomatis and 2,867 N. gonorrhoeae vaginal swab test results were used in the data analysis. 13 subjects had unknown CT patient infected status and 14 subjects with unknown GC patient infected status, whose results were excluded from calculations.
Data Source: Subjects were enrolled into the clinical study from STD, OB/GYN, teen, and family planning clinics. Specimens collected included one urine specimen, one patient-collected vaginal swab, one clinician-collected vaginal swab, and two randomized endocervical swabs from each subject.
Annotation Protocol:
- Subject infection status (infected/non-infected with C. trachomatis or N. gonorrhoeae) was determined based on a patient infected status algorithm.
- This algorithm used endocervical swab and urine specimen results from two commercially available Nucleic Acid Amplification Tests (NAATs): the APTIMA Combo 2 Assay and another commercially available NAAT.
- Subjects were considered infected if two of the four endocervical swab and urine specimens tested positive (one specimen testing positive in each NAAT).
- Subjects were considered non-infected if less than two reference NAAT results were positive.
- Samples that were APTIMA Combo 2 Assay positive and patient infected status negative (apparent false positives) were tested in alternate TMA assays targeting unique sequences, but these results were not used to change the original patient categorizations.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Multi-center clinical study on vaginal swab specimens.
Sample Size: 1,464 symptomatic and asymptomatic female subjects. A total of 2,868 C. trachomatis and 2,867 N. gonorrhoeae vaginal swab test results were used in the data analysis.
Standalone Performance:
- Analytical Sensitivity:
- Chlamydia trachomatis: 1 Inclusion-Forming Unit (IFU) per assay (7.25 IFU/swab, 5 IFU/mL urine) for all 15 C. trachomatis serovars.
- Neisseria gonorrhoeae: 50 cells/assay (362 cells/swab, 250 cells/mL urine) for 57 different clinical isolates.
- Analytical Specificity: Tested 154 culture isolates (86 urogenital, 68 phylogenetic cross-section) including bacteria, fungi, yeast, parasites, and viruses. Only C. trachomatis and N. gonorrhoeae samples produced positive results.
- Interference Studies: No interference observed with common vaginal swab and urine substances.
Key Results:
C. trachomatis Sensitivity and Specificity (Overall vs. Patient Infected Status)
- Patient-Collected Vaginal Swab (All): Sensitivity 96.6% (95% CI: 92.8 - 98.8), Specificity 97.8% (95% CI: 96.8 - 98.5)
- Clinician-Collected Vaginal Swab (All): Sensitivity 96.7% (95% CI: 92.9 - 98.8), Specificity 97.1% (95% CI: 96.0 - 97.9)
N. gonorrhoeae Sensitivity and Specificity (Overall vs. Patient Infected Status)
- Patient-Collected Vaginal Swab (All): Sensitivity 98.7% (95% C.I.: 93.0 - 100), Specificity 99.6% (95% C.I.: 99.0 - 99.8)
- Clinician-Collected Vaginal Swab (All): Sensitivity 96.2% (95% C.I.: 89.2 - 99.2), Specificity 99.4% (95% C.I.: 98.8 - 99.7)
Predictive Values for Hypothetical Prevalence Rates:
- C. trachomatis: Overall sensitivity 96.1%, specificity 97.9%. PPV and NPV calculated for prevalence rates from 2% to 30%.
- Example: At 10% prevalence, PPV is 85.5% and NPV is 99.5%.
- N. gonorrhoeae: Overall sensitivity 98.0%, specificity 99.1%. PPV and NPV calculated for prevalence rates from 2% to 30%.
- Example: At 10% prevalence, PPV is 90.8% and NPV is 99.8%.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
C. trachomatis:
- Patient-Collected Vaginal Swab (Overall):
- Sensitivity: 96.6% (95% C.I. 92.8 - 98.8)
- Specificity: 97.8% (95% C.I. 96.8 - 98.5)
- PPV: 86.0%
- NPV: 99.5%
- Clinician-Collected Vaginal Swab (Overall):
- Sensitivity: 96.7% (95% C.I. 92.9 - 98.8)
- Specificity: 97.1% (95% C.I. 96.0 - 97.9)
- PPV: 82.5%
- NPV: 99.5%
N. gonorrhoeae:
- Patient-Collected Vaginal Swab (Overall):
- Sensitivity: 98.7% (95% C.I. 93.0 - 100)
- Specificity: 99.6% (95% C.I. 99.0 - 99.8)
- PPV: 90.4%
- NPV: 99.9%
- Clinician-Collected Vaginal Swab (Overall):
- Sensitivity: 96.2% (95% C.I. 89.2 - 99.2)
- Specificity: 99.4% (95% C.I. 98.8 - 99.7)
- PPV: 90.4%
- NPV: 99.8%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3390
Neisseria spp. direct serological test reagents.(a)
Identification. Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identifyNeisseria spp. from cultured isolates. Additionally, some of these reagents consist ofNeisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence ofNeisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusNeisseria, 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.(b)
Classification. Class II (performance standards).
0
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
1
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 (858) 410-8000 (858) 410-8622 (FAX)
Company Contact: Alan Maderazo, Ph.D., RAC Regulatory Affairs Specialist (858) 410-8332 (858) 410-8622(FAX) alanma@gen-probe.com
2
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 |
| test for the in vitro diagnostic detection of Chlamydia | |
| trachomatis and/or Neisseria gonorrhoeae | |
| Classification Names: | DNA Probe, Nucleic Acid Amplification, Chlamydia |
| DNA Reagents, Neisseria |
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
3
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)
4
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.
5
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.
Gen-Probe Incorporated
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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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10
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
and
Safety
| 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) | ||||||||
| NA | PTIMA Combo 2 Assa | /mptom Stat | |||||||
| tient Infecte Status | ndocervic | ||||||||
| Swab | Urine | Endocervica | |||||||
| 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
| Status | NAAT 1 | NAAT 2 (APTIMA Combo 2 Assay) | APTIMA Combo 2 Assay | Symptom Status | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Endocervical | |||||||||||
| Swab | Urine | Endocervical | |||||||||
| Swab | Urine | Patient- | |||||||||
| Collected | |||||||||||
| Vaginal Swab | Clinician- | ||||||||||
| Collected | |||||||||||
| 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
| Status | NAAT 1 | NAAT 2 (APTIMA Combo 2 Assay) | APTIMA Combo 2 Assay | Symptom Status | Total | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Endocervical | ||||||||||
| Swab | Urine | Endocervical | ||||||||
| Swab | Urine | Patient- | ||||||||
| Collected | ||||||||||
| Vaginal Swab | Clinician- | |||||||||
| Collected | ||||||||||
| Vaginal Swab | Symptomati | |||||||||
| c | Asymptomati | |||||||||
| 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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| and Effectiveness | |
|---|---|
| Safety | |
| of | |
| .lary | |
| 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 | ||||||||||||
| 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 | ||||||||||||
| 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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| Status |
|---|
| - |
| Property |
| 1 |
| 1 |
| Vaginal Swab Specimens vs. Patient Infected Status |
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
| a at 10 alle the la |
| 1 1993 1 |
| ombe |
| - |
| DITTS |
| necificity: |
| 1 |
| MITS UNIVERSITY CAS CALLERY CAR CALTACA WA |
| Ancitivity and |
| ver |
-
|
| Onom
044
. |
| 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 | ||||||||
| TT | FP | TN | FN | Sensitivity | 95% C.I. | specificit | 95% C.I. | ||||
| Patient-Collected Vaginal Swab | Asymptomatic | 659 | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | ||||||||
| 22 | くな | ||||||||||
| খ | ୧୦ર | 100 | 100 | ||||||||
| 84.6 - | 99.7 | 100 | |||||||||
| 198.8 - | |||||||||||
| All | 423 | 76 | ep | 340 | 98.7 | 100 | |||||
| 93.0 - | 99.6 | 99.0 - 99.8 | |||||||||
| 'linician-Collected Vaginal Swab Symptomatic | 807 | ਟ ਤੇ | ર્દ ૮ | 747 | 1 | 96.4 | તેત્વે છ | ||||
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (%) | (%) | ||||||||||||
| 217 | I 3 | 203 | 92.9 | ರಿಗೆ ಕೆಳಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರ | |||||||||
| ्२० । | 100 | ||||||||||||
| atient-Collect aginal Swab | C | ો તેર | 164 | -00000000 | 100 | ಕ್ಷಣ ಸಿಕ್ಷಣ ಸ್ಥಳದ ಪ್ರತಿ ಸ್ಥೆಗಳು ಸೇರಿ ಸೇರಿ ಸೇರಿ ಸೇರಿ ಸೇರಿ ಸ | 일 중 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 | ್ದ ಕ್ಷತ್ರ ಕ್ರಿ ಕೃತ ಕೃತ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ಷಿತ್ರ ಪ್ರಸಿ | |||||
| ದ | 100 | ||||||||||||
| 261 | 100 | ||||||||||||
| S | I dd | 100 | |||||||||||
| 9 | ----------- | ទ្ធសន្ធមាន ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នា | ള്ള ജ്വീട്ടില്ല് ജീവിച്ചിരിച്ചു. അവലംബം വേട്ടി ജീവിച്ച വിവ | ||||||||||
| 201 067 | 1/11 00 T | ||||||||||||
| 47 | 1001 | ||||||||||||
| ALL | 1423 | 14 4 6 0 0 0 0 0 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 | 340 | โ | ហូតមួយ ១០០០ ដក | 001 1001 | |||||||
| 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 | ക്രിക്കുന്നത്. അവലംബം അവലംബം പ്രവർത്തിച്ചു. അവലംബം കുറച്ചു വിവരുന്നു വാഹ്യത്തിൽ നിന്നും വിശ്വാസ്ത്രിക്കുന്നു. അവലംബം അവലംബം അവലംബം | ||||||||||||
| nician-Collec | 227 | 100 | 100 | 100 | |||||||||
| aginal Swa | 100 | ||||||||||||
| ర్లాల | 75.0 | 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 |
- $61. - 88.8.8 - 78.82 | | | | |
| | P | | | | | | | 100 | 100) | | | | |
| | S | | | | | | | 100 | 100
(47.8 - 15.8 - | റ്റും ഉപ്പുഴി സംഭവ ഗ്ഗങ്ങളുടെ ഭാഗം ഗ്ഗങ്ങളുടെ ഭ | 001 1666 (001 6666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666 | ತ್ತಿದ್ದ ಸ್ನೇಶ್ವಿ ಪ್ರಶಸ್ತಿ ಶ್ವಿತ್ವ | ತ ಕ್ರಿ ಪ್ಲೆ ಶ್ವಿತ ಶ್ವಿ ಶ್ವಿ ಶ್ವಿ ಶ್ವಿ ಶ್ವಿ ಶ್ರೀ ಶೇಖ |
| | 9 | | | | | | | | | 001 901 9186 | 99.6) | | |
| | 1 | | | | | | | | | | 001 | | |
| | | ន គួរ និង និង និង ន | 7 – 68 – 68 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – | 000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | កម្ពុជា និងប្រជាជនជាតិ | 00-0000000 | ស់ ហុស្សនា ១០០ នាក់ ប្រជាជន ប្រជាជន ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជា | ារ សារ លោក | 68.3 - 98.8) | | តែ និង និង និង និង ន | | |
| | ALL | 444 | | | | | | 96.2 | | 99.4 | 98.8 - 99.7 | 90.4 | ర్తి 8 |
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20
Prevalence
The prevalence of C. trachomatis and/or N. gonorrhoeae disease in patient populations depends on risk factors such as age, gender, the presence of symptoms, the type of clinic, and the test method. A summary of the prevalence of three C. trachomatis and N. gonorrhoeae disease outcomes as determined by the APTIMA Combo 2 Assay is shown in Table 7 for the vaginal swab specimen multi-center clinical study by clinical site and overall.
Confidential
21
| Summary of Safety and Effectiveness |
|---|
| K032554 |
| Site | Patient-Collected Vaginal Swab, % Prevalence (# positive/# tested) | Clinician-Collected Vaginal Swab, % Prevalence (# positive/# tested) | ||||
|---|---|---|---|---|---|---|
| CT+/GC+ | CT+/GC- | CT-/GC+ | CT+/GC+ | CT+/GC- | CT-/GC+ | |
| 1 | 1.8 | |||||
| (4/220) | 16.4 | |||||
| (36/220) | 4.1 | |||||
| (9/220) | 3 | |||||
| (7/230) | 15.7 | |||||
| (36/230) | 3.5 | |||||
| (8/230) | ||||||
| 2 | 9.6 | |||||
| (19/198) | 18.7 | |||||
| (37/198) | 6.6 | |||||
| (13/198) | 9.5 | |||||
| (19/199) | 18.1 | |||||
| (36/199) | 7 | |||||
| (14/199) | ||||||
| 3 | 0.9 | |||||
| (1/111) | 9 | |||||
| (10/111) | 2.7 | |||||
| (3/111) | 0.9 | |||||
| (1/113) | 9.7 | |||||
| (11/113) | 1.8 | |||||
| (2/113) | ||||||
| 4 | 0.4 | |||||
| (1/266) | 9 | |||||
| (24/266) | 1.9 | |||||
| (5/266) | 0.4 | |||||
| (1/267) | 11.2 | |||||
| (30/267) | 2.2 | |||||
| (6/267) | ||||||
| 5 | 0.5 | |||||
| (1/199) | 7.5 | |||||
| (15/199) | 0.5 | |||||
| (1/199) | 0.5 | |||||
| (1/199) | 7 | |||||
| (14/199) | 0.5 | |||||
| (1/199) | ||||||
| 6 | 2.8 | |||||
| (8/290) | 10 | |||||
| (29/290) | 5.5 | |||||
| (16/290) | 2 | |||||
| (6/296) | 12.2 | |||||
| (36/296) | 5.4 | |||||
| (16/296) | ||||||
| 7 | 0 | |||||
| (0/102) | 11.8 | |||||
| (12/102) | 0 | |||||
| (0/102) | 0 | |||||
| (0/102) | 9.8 | |||||
| (10/102) | 0 | |||||
| (0/102) | ||||||
| 8 | 0 | |||||
| (0/48) | 8.3 | |||||
| (4/48) | 2.1 | |||||
| (1/48) | 0 | |||||
| (0/51) | 7.8 | |||||
| (4/51) | 2 | |||||
| (1/51) | ||||||
| All | 2.4 | |||||
| (34/1434) | 11.6 | |||||
| (167/1434) | 3.3 | |||||
| (48/1434) | 2.4 | |||||
| (35/1457) | 12.1 | |||||
| (177/1457) | 3.3 | |||||
| (48/1457) |
0
Table 7: Prevalence of C. trachomatis and/or N. gonorrhoeae Disease as Deternined by the APTIMA Combo 2 Assay Results by Clinical Site
Gen-Probe Incorporate
22
Positive and Negative Predictive Values for Hypothetical Prevalence Rates
The estimated positive and negative predictive values (PPV and NPV) for different hypothetical prevalence rates using the APTIMA Combo 2 Assay are shown in Tables 8 and 9 for C. trachomatis and N. gonorrhoeae, respectively. These calculations are based on a hypothetical prevalence and the overall sensitivity and specificity calculated from the patient infected status for two multi-center clinical studies; the endocervical swab, male urethral swab, and urine specimen clinical study and the vaginal swab specimen clinical study. The overall sensitivity and specificity for C. trachomatis was 96.1% and 97.9%, respectively (Table 8). The overall sensitivity and specificity for N. gonorrhoeve was 98.0% and 99.1%, respectively (Table 9). The actual PPV and NPV calculated using the clinical study data are shown in Tables 4 and 6 for C. trachomatis and N. gonorrhoeae, respectively
Table 8: Positive and Negative Predictive Values for Hypothetical Prevalence Rates- C. trachomatis
| Prevalence Rate (%) | Sensitivity (%) | Specificity (%) | Positive Predictive
Value (%) | Negative Predictive
Value (%) |
|---------------------|-----------------|-----------------|----------------------------------|----------------------------------|
| 2 | 95.9 | 98.2 | 52.1 | 99.9 |
| 5 | 95.9 | 98.2 | 73.7 | 99.8 |
| 10 | 95.9 | 98.2 | 85.5 | 99.5 |
| 15 | 95.9 | 98.2 | 90.4 | 99.3 |
| 20 | 95.9 | 98.2 | 93.0 | 99.0 |
| 25 | 95.9 | 98.2 | 94.7 | 98.6 |
| 30 | 95.9 | 98.2 | 95.8 | 98.2 |
| Table 9: Positive and Negative Values for Hypothetical Prevalence Rates- N. gonorrhoeae | ||||
|---|---|---|---|---|
| Prevalence Rate (%) | Sensitivity (%) | Specificity (%) | Positive Predictive
Value (%) | Negative Predictive
Value (%) |
|---------------------|-----------------|-----------------|----------------------------------|----------------------------------|
| 2 | 97.8 | 98.9 | 64.5 | 100 |
| 5 | 97.8 | 98.9 | 82.4 | 99.9 |
| 10 | 97.8 | 98.9 | 90.8 | 99.8 |
| 15 | 97.8 | 98.9 | 94.0 | 99.6 |
| 20 | 97.8 | 98.9 | 95.7 | 99.4 |
| 25 | 97.8 | 98.9 | 96.7 | 99.3 |
| 30 | 97.8 | 98.9 | 97.4 | 99.1 |
23
Assay Control Performance
Control RLU data were generated as part of the vaginal swab specimen clinical study. A summary of the APTIMA Positive Control, CT/Negative Control, GC and APTIMA Positive Control, GC/Negative Control, CT performance during the clinical study is presented in Table 10.
| Control | Statistics | Total RLU (x1000) |
|---|---|---|
| Positive, CT/Negative, GC | Maximum | 1996 |
| 75th Percentile | 1279 | |
| Median | 1135 | |
| 25th Percentile | 933 | |
| Minimum | 174 | |
| Positive, GC/Negative, CT | Maximum | 1420 |
| 75th Percentile | 1255 | |
| Median | 1169 | |
| 25th Percentile | 1084 | |
| Minimum | 249 |
Table 10: Distribution of Total RLU of the APTIMA Assay Controls from the Vaginal Swab Specimen Clinical Study
24
Conclusions from the Clinical Data
The non-clinical and clinical study results support the use of clinician-collected and patient-collected vaginal swab specimens in the GEN-PROBE APTIMA Combo 2 Assay for the detection of C. trachomatis and N. gonorrhoeae. The GEN-PROBE APTIMA Vaginal Swab Specimen Collection Kit provides the necessary materials to allow for the testing of clinician-collected or patient-collected vaginal specimens in the APTIMA Combo 2 Assay. Use of this ancillary kit broadens the application of the APTMA Combo 2 Assay as a diagnostic tool to provide information that measurably contributes to a diagnosis of C. trachomatis and N. gonorrhoeae infection.
The results of the clinical study demonstrate reasonable evidence that when the APTIMA Combo 2 Assay and the APTIMA Vaginal Swab Specimen Collection Kit are labeled as proposed, the GEN-PROBE APTIMA Combo 2 Assay is safe and effective for its stated intended use.
Application of the APTIMA Vaginal Swab Specimen Collection kit in the APTIMA Combo 2 Assay provides performance that is substantially equivalent to that of the previously cleared claims (K003395) for the detection of C. trachomatis and N. gonorrhoeae which is indicative of it's safety and effectiveness.
Contraindications and Cautions
There are no contraindications or cautions.
25
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/25/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized symbol resembling three overlapping lines, with the bottom line having a wavy appearance. The symbol is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA", which is arranged in a circular fashion around the symbol.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
DEC 3 1 2003
Alan Maderazo, Ph.D. RAC Regulatory Affairs Specialist Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121-1589
Re: K032554
Trade/Device Name: GEN-PROBE® APTIMA® Combo 2 Assay Regulation Number: 21 CFR 866.3390 Regulation Name: Neisseria spp. Direct Serological Test Reagents Regulatory Class: Class II Product Code: LSL, MKZ Dated: December 24, 2003 Received: December 29, 2003
Dear Dr. Maderazo:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
26
Page 2 -
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Steven Putman
Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
27
Indications for Use
K032554 510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________
Device Name:
GEN-PROBE® APTIMA® Combo 2 Assay
Indications for 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.
Indications for 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.
Prescription Use
(Part 21 CFR 801 Subpart D)
✓
AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Saqartzonl 12/31/03
Division Sien-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k)_K0325554