(78 days)
The APTIMA® Assay for Neisseria gonorrhoeae is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC) to aid in the diagnosis of gonococcal urogenital disease. The assay may be used to test the following specimens from symptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; and female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: cliniciancollected endocervical and vaginal swab specimens; and patient-collected vaginal swab specimens and female and male urine specimens. The assay is also intended for use with the testing of gynecological specimens, from both symptomatic and asymptomatic patients, collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System.
Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Assay for Neisseria gonorrhoeae to include PreservCyt liquid Pap specimens (collected and processed by the Cytyc ThinPrep 2000 Processor) as acceptable testing specimens. The ancillary kit formulated for this specific application is the commercially available GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for use regarding decontamination and specimen processing procedures. The APTIMA Specimen Transfer Kit may only be used in conjunction with GEN-PROBE APTIMA Assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae.
The provided document describes the GEN-PROBE APTIMA Assay for Neisseria gonorrhoeae, specifically its expanded indication for use with ThinPrep Specimens. The acceptance criteria and the study proving the device meets these criteria are detailed below.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for sensitivity and specificity are not explicitly stated as numerical targets in the document. However, the study results are presented as the "Summary of Clinical Performance Data" and indicate the device's performance attributes. The general expectation for such a diagnostic assay is high sensitivity and specificity. The reported performance is based on the clinical study.
| Metric | Acceptance Criteria (Implied / Not Explicitly Stated) | Reported Device Performance (Overall) |
|---|---|---|
| Sensitivity | High sensitivity expected | 92.3% (12/13) |
| Specificity | High specificity expected | 99.8% (1630/1633) |
2. Sample Sizes and Data Provenance
- Test Set Sample Size: 1,646 symptomatic and asymptomatic female subjects were evaluated in the clinical study. (Page 8)
- Data Provenance: The data was collected from a prospective multi-center clinical study (Page 8). The study subjects were enrolled from sites with GC prevalence ranging from 0.0% to 5.0% (Page 8). While the exact country of origin is not explicitly stated, the context of an FDA submission (K062440) for a device from "San Diego, California" implies the study was likely conducted in the United States.
3. Number of Experts and Qualifications for Ground Truth
The document does not mention the use of experts to establish ground truth for the clinical study.
4. Adjudication Method for the Test Set
The adjudication method used to establish the "patient infected status" (ground truth) for the clinical study was based on a reference standard involving two other tests:
- The APTIMA Combo 2 Assay (for Chlamydia trachomatis and Neisseria gonorrhoeae).
- The APTIMA GC Assay (performed on endocervical swab specimens). (Page 8)
The criteria were:
- Infected Patient Status: Both reference NAATs (APTIMA Combo 2 Assay and APTIMA GC Assay on endocervical swab) were required to be positive.
- Non-Infected Patient Status: At least one reference NAAT was required to be negative.
- Inconclusive: If an equivocal result was obtained from any one of the reference NAATs, the patient infected status was categorized as inconclusive, and these specimens were not included in sensitivity and specificity calculations. (Page 8)
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was mentioned. The study focuses on the performance of the device itself against a defined ground truth, not on human readers with or without AI assistance.
6. Standalone Performance
Yes, a standalone (algorithm only) performance study was performed. The clinical study directly evaluated the performance of the APTIMA GC Assay in PreservCyt liquid Pap specimens against a defined patient infected status (ground truth) derived from other laboratory tests, without human-in-the-loop performance described. (Page 8)
7. Type of Ground Truth Used
The ground truth used was based on a composite reference standard derived from the results of two other Nucleic Acid Amplification Tests (NAATs) – the APTIMA Combo 2 Assay and the APTIMA GC Assay – performed on endocervical swab specimens. Specifically, two positive reference NAATs defined an infected patient, and at least one negative defined a non-infected patient. (Page 8)
8. Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or its sample size for model development. Diagnostic assays like this typically undergo extensive analytical validation to determine performance characteristics (e.g., limit of detection, specificity) and then clinical validation using a distinct clinical sample set. The analytical studies describe testing with various organisms and dilutions, which might be considered part of the development and refinement process, but not a formally delineated "training set" in the context of machine learning.
9. How Ground Truth for the Training Set Was Established
Since a distinct "training set" is not described, the method for establishing its ground truth is not provided. For the analytical studies (e.g., Limit of Detection, Analytical Specificity), organism concentrations were precisely controlled by direct comparison/dilution of clinical isolates or by spiking known concentrations of organisms/cells into samples. (Page 3-4)
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APTIMA Assay for Neisseria gonorrhoeae – Expanded Indication: ThinPrep Specimens
510(k) SUMMARY 5.0
NOV 7 2006
GEN-PROBE® APTIMA® Assay for Neisseria gonorrhoeae
General Information
| Submitted By: | Company Contact: |
|---|---|
| Gen-Probe Incorporated10210 Genetic Center DriveSan Diego, California 92121phone: (858) 410-8000fax: (858) 410-8622 | E. Joseph McMullenAssociate Director, Regulatory Affairsphone: (858) 410-8649fax: (858) 410-8622e-mail: josephm@gen-probe.com |
| Trade Name: | GEN-PROBE® APTIMA® Assay for Neisseria gonorrhoeae |
| Common or Usual Name: | rRNA target-amplified nucleic acid probe test for the in vitrodiagnostic detection of Neisseria gonorrhoeae |
| Classification Name: | DNA Reagents, Neisseria |
| Classification Code: | Medical Specialty: MicrobiologyProduct Code: LSLRegistration Number: CFR 866.3390Device Class: 2Description: Reagents used to identify Neisseria spp. directlyfrom clinical specimens or cultured isolates derived fromclinical specimens. The identification aids in the diagnosis ofdisease caused by bacteria belonging to the genus Neisseria,such as epidemic cerebrospinal meningitis, meningococcaldisease, and gonorrhea, and also provides epidemiologicalinformation on diseases caused by these microorganisms |
Substantially Equivalent Devices:
GEN-PROBE® APTIMA® Assay for Neisseria gonorrhoeae
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APTIMA Assay for Neisseria gonorrhoeae – Expanded Indication: ThinPrep Specimens
Device Description
Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Assay for Neisseria gonorrhoeae to include PreservCyt liquid Pap specimens (collected and processed by the Cytyc ThinPrep 2000 Processor) as acceptable testing specimens. The ancillary kit formulated for this specific application is the commercially available GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for use regarding decontamination and specimen processing procedures. The APTIMA Specimen Transfer Kit may only be used in conjunction with GEN-PROBE APTIMA Assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae.
Intended Use
APTIMA Assay for Neisseria gonorrhoeae package insert:
The APTIMA® Assay for Neisseria gonorrhoeae is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC) to aid in the diagnosis of gonococcal urogenital disease. The assay may be used to test the following specimens from symptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; and patient-collected female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: clinician-collected endocervical and vaginal swab specimens; and patient-collected vaginal swab specimens' and female and male urine specimens. The assay is also intended for use with the testing of gynecological specimens collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System.
1 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.
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APTIMA Assay for Neisseria gonorrhoeae - Expanded Indication: ThinPrep Specimens
Ancillary Kit package insert:
The GEN-PROBE APTIMA Specimen Transfer Kit is only for use with GEN-PROBE APTIMA Assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae. The GEN-PROBE APTIMA Specimen Transfer Kit allows for APTIMA Assay testing of gynecological specimens collected and processed by the Cytyc ThinPrep 2000 Processor according to the instructions provided.
APTIMA Assay for Neisseria gonorrhoeae
A complete description of the APTIMA Assay for Neisseria gonorrhoeae is provided in the commercialized package insert.
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APTIMA Assay for Neisseria gonorrhoeae – Expanded Indication: ThinPrep Specimens
Summary of Non-Clinical (Analytical Laboratory) Performance Data
Limit of Detection (Analytical Sensitivity)
N. gonorrhoeae analytical sensitivity (limit of detection) was determined by directly comparing dilutions of 51 different clinical isolates in culture and in the APTIMA GC Assay. The analytical sensitivity claim for the assay is 50 cells/assay (362 cells/swab, 250 cells/mL urine, 487.5 cells/mL PreservCyt Solution liquid Pap).
Analytical Specificity
A total of 154 culture isolates were evaluated using the APTIMA GC 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, U. urealyticum and the viruses were tested at 1.0x106 cells/assay in Kova-trol/urine transport media and 60 organisms were tested in swab transport media. C. psittaci VR601 was tested at 8x101 cells/assay and C. psittaci VR125 was tested at 1x10 cells/assay. C. pneumoniae was tested at 4x103 cells/assay and U. urealyticum was tested at 6.7x106 cells/assay. The viruses were tested as follows: (a) herpes simplex virus I: 2.5x104 TCIDs/assay, (b) herpes simplex virus II: 6.0x104 TCIDs/assay, (c) human papillomavirus 16: 2.9x106 DNA copies/assay and (d) cytomegalovirus: 4.8x10 ³ cells/assay. The list of organisms tested is shown in Table 1.
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APTIMA Assay for Neisseria gonorrhoeae – Expanded Indication: ThinPrep Specimens
| 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 | Peptostreptococcusanaerobius |
| Agrobacterium radiobacter | Herpes simplex virus I | Peptostreptococcusproductus |
| Alcaligenes faecalis | Herpes simplex virus II | Plesiomonas shigelloides |
| Bacillus subtilis | Human papilloma virus 16 | Propionibacterium acnes |
| Bacteriodes fragilis | Kingella denitrificans | 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 | Staphylococcussaprophyticus |
| Chromobacterium violaceum | Moraxella osloensis | Staphylococcus aureus |
| Citrobacter freundii | Morganella morganii | Staphylococcusepidermidis |
| 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 | Streptomyces griseinus |
| Enterobacter cloacae | Neisseria cinerea (4) | Trichomonas vaginalis |
| Enterococcus avium | Neisseria denitrificans | 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) |
Table 1: APTIMA GC Assay Analytical Specificity
(n) = Number of strains tested
All organisms tested produced a negative result in the APTIMA GC Assay.
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Interference Studies
The following interfering substances were individually spiked into swab, PreservCyt liquid Pap, and/or urine specimens: 10% blood, contraceptive jelly, spermicide, moisturizer, hemorrhoidal anesthetic, body oil, powder, anti-fungal cream, vaginal lubricants, feminine spray and leukocytes (1x10 cells/mL). The following interfering substances were individually spiked into urine specimens: 30% blood, urine analytes, protein, glucose, ketones, bilirubin,
nitrate, urobilinogen, pH 4 (acidic), pH 9 (alkaline), leukocytes (1x106 cellular debris, vitamins, minerals, acetaminophen, aspirin and ibuprofen. All were tested for potential assay interference in the absence and presence of GC at the estimated rRNA equivalent of 50 GC cells/assay (250 fg/assay). The rRNA equivalents were calculated based on the genome size and estimated DNA:RNA ratio/cell of each organism. No interference was observed with any of the tested substances. No inhibitors of amplification were observed in the APTIMA GC Assay.
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APTIMA Assay for Neisseria gonorrhoeae - Expanded Indication: ThinPrep Specimens
Recovery
Escherichia coli, Gardnerella vaginalis, Lactobacillus acidophilus, Bacteroides ureolyticus and Staphylococcus epidermidis (1 x 10° cells/assay) were added to samples containing the rRNA equivalent of approximately 50 N. gonorrhoeae cells (250 fg). These additions did not interfere with the amplification and detection of N. gonorrhoeae rRNA using the APTIMA GC Assay.
Liquid Pap Specimen Stability Studies
Data to support the recommended shipping and storage conditions for PreservCyt Solution liquid Pap samples were generated with negative processed and unprocessed liquid Pap samples. For the unprocessed samples, four pools of PreservCyt Solution samples were tested after being stored in the Cytyc PreservCyt Solution vial. Each specimen pool was spiked with 50-100 CFU GC/assay, held at 2℃, 10℃, and 30℃, then tested at baseline and on days 5, 7, 8, 14, 18, 21, 25 and 36. All of the spiked samples were positive for GC at all times and temperatures. For the processed samples, four pools of PreservCyt Solution samples were used to determine processed specimen stability at 2℃ to 30℃. Each negative sample pool was spiked with 50-100 IFU GC/assay, then tested at baseline. Prior to processing, the PreservCyt Solution samples were stored at 30°C for seven (7) days to simulate the time lapse between sample collection, Pap processing and shipment to a microbiology testing lab. After seven days at 30℃, 1 mL aliquots of each pool were transferred to an APTIMA Specimen Transfer Tube and tested at baseline before being placed at 2℃, 10℃, and 30℃. The processed samples were then tested for 17 days stored at 30°C and 36 days stored at 2°C to 10°C. All of the spiked samples were positive for GC at all times and temperatures. Data to support longer storage conditions were generated from four pools of negative processed PreservCyt Solution samples tested at below freezing temperatures. Each pool was spiked with 50-100 IFU CT/assay, then tested at baseline. Each pool was first placed at 30°C for 14 days and then stored at -20°C or -70°C over the course of 106 days. All of the spiked samples were positive for GC at all times and temperatures.
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TIMA Assay for Neisseria gonorrhoeae – Expanded Indication: ThinPrep Specim ROBE INCORPORA
recisio
iters. Each of the resulting Pap-STM samples was tested once in the APTIMA GC Assay. A total of five runs were per into 14 APTIMA Transfer Tubes as per the APTIMA Specimen Transfer Kit package insert. The operators were blind ay period for 140 results at the 0.1, 0.5, and 50 CFU level. There were 136 valid results and 4 invalid results for spiked vials were divided between two operators vortexed the vials and then transferred 14 aliquots (1 t specimen within-laboratory precision with the APTIMA GC Assay was determined by spiking PreservCyt vials ntrol panel. The invalid results were due to a misplacement of a TTU in the Leader HC+. The results are summarized in per reaction) and unspiked PreservCyt vials were tested as positive and negative controls. Ten vials spiked at each per vial (0.1 CFU per reaction) and 100 GC CFU per vial (0.5 CFU per reaction). Vials containing 10,000 GC CF
| Table 2: APTIMA GC Assay Within-laboratory Precision Data for PreservCyt Using a 4-Member Precision Panel Containing 0 | .o 500 CFU/mL GC Cells. |
|---|---|
| . | - | MAR 14 FRE RALL in Lear Fri | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | ા ક | NA | 0.3 | ામિ | 0 | NA | ાં ક | 1.2 | 100 | 136 | 1 36. | 1 | 1 | |
| ને રિ | 250. | 0.0 | 0.0 | 2.4 | 1 35.7 | 3.9 | 220.7 | 5636.8 | 100------------ | 140 | 140 | SQ | 500 | ು |
| 87.2 | 1056.0 | 12.4 | 150.4 | 14.0 | പ്പുകളുടെ ഒരു പ്രവരിച്ചു. അവലം പ്രവരിച്ചു. അവലം പ്രവരിച്ചു. അതിനും പ്രവരിച്ചു. അതിനും വിശ്വാസം പ്രവരിച്ചു. അതിനുശേഷം പ്രവരിച്ചു. അതിനുകളും പ്രവരിച്ചു. അതിനുകളും പ്രവരിച്ചു. | 85.2 | 1031.3 | 1211.1 | 80.7 | 113 | 140 | ૫.ક | LO | 0 |
| 245.4 | 769.8 | 0.0 | 00 | 42.2 | 1 32 5------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | 241.7 | 758.3 | 313.7 | 27.9 | ર્જી | 14C | 0.1 | 0 | |
| (%) | x1000 | 1%) | (x1000 | ിക | x1000 | ్రైవే | x1000------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | x1000 | Agrmt. | Agreed | t | CENTXI | CFU.mL reservCy | Member |
| CV | SD | ে | SD | CV | &D | CV | ਣ D | de arகாப | ్రాప్ | Panel | ||||
| Total | Operator | Between-Day | vithin-Operator | |||||||||||
| Between- |
our invalid results due to a misplaced TTU in the Leade
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OBE INCORPORATED
PTIMA Assay for Neisseria gonorrhoeae - Expanded Indication: ThinPrep Specimens
Summary of Clinical Performance Data
A prospective multi-center clinical study was conducted to evaluate the use of the PreservCyt transport medium (a component of the ThinPrep 2000 System) as an alternative medium for gynecological specimens for the detection of N. gonorrhoeae by the APTIMA GC Assay. One thousand six hundred forty-six (1,646) symptomatic and asymptomatic female subjects attending OB/GYN, family planning, public health, women's, and STD clinics were evaluated in the clinical study. Of the 1,646 evaluable subjects, 1,287 were asymptomatic subjects and 359 were symptomatic subjects (Table 3). Subjects were enrolled from sites with GC prevalence that ranged from 0.0% to 5.0%. Two specimens were collected from each eligible subject: one PreservCyt liquid Pap specimen and one endocervical swab specimen. PreservCyt liquid Pap specimens were collected with the spatula/cyto-brush or a broom-like brush cervical sampling device. The distribution of cervical sampling devices is summarized in Table 4 by specimen collection site and overall. PreservCyt liquid Pap specimens were processed in accordance with the ThinPrep 2000 Processor Operator's Manual and APTIMA Specimen Transfer Kit package insert. After processing the PreservCyt liquid Pap specimen with the ThinPrep 2000 Processor, the specimen was transferred into the APTIMA Specimen Transfer Kit for testing with the APTIMA GC Assay. Sensitivity and specificity of the APTIMA GC Assay in PreservCyt liquid Pap specimens were calculated by comparing results to the patient infected status. The algorithm included APTIMA Combo 2 Assay and APTIMA GC Assay results in endocervical swab specimens. Both reference NAATs were required to be positive to establish an infected patient status. At least one reference NAAT was required to be negative to establish a non-infected patient status. If an equivocal result was obtained from any one of the reference NAATs, the patient infected status was categorized as inconclusive; these specimens were not included in the sensitivity and specificity calculations. Table 4 shows the sensitivities and specificities of the APTIMA GC Assay by symptom status and overall. Overall sensitivity was 92.3% (12/13). In symptomatic and asymptomatic subjects, sensitivities were 100% (7/7) and 83.3% (5/6), respectively. Overall specificity was 99.8% (1630/1633). In symptomatic and asymptomatic subjects, specificities were 99.4% (350/352) and 99.9% (1280/1281), respectively. Table 5 shows the sensitivities and specificities of the APTIMA GC Assay by specimen collection site and overall. Sensitivities ranged from 80.0% to 100%. Specificities ranged from 99.0% to 100%.
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I-PROBE INCORPORAT
IMA Assay for Neisseria gonorrhoeae – Expanded Indication: ThinPrep Speciment
able 3: Distribution of Cervical Sampling Device Used for PreservCyt Liquid Pap Specime
| Cervical Sampling Device Used | Clinical Collection Site | Total | |||||
|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | ||
| Spatula/Cytobrush | 0 | 124 | 475 | 287 | 57 | 364 | 1307 |
| Broom-Type Device | 100 | 0 | 0 | 0 | 240 | 0 | 340 |
able 4: Performance of the APTIMA GC Assay in PreservCyt Liquid Pap Specimens by Symptom Stat
| APTIMA GCPreservCyt Result | +/+ | +/- | -/+ | -/- | Sensitivity (%)(95% CI) | Specificity (%)(95% CI) | |
|---|---|---|---|---|---|---|---|
| Symptomatic | Positive | 7 | 0 | 0 | 2 | 100 (7/7)(59.0 - 100) | 99.4 (350/352)(98.0 - 99.9) |
| Negative | 0 | 0 | 0 | 350 | |||
| Total | 7 | 0 | 0 | 352 | |||
| Asymptomatic | Positive | 5 | 0 | 0 | 1 | 83.3 (5/6)(35.9 - 99.6) | 99.9 (1280/1281)(99.6 - 100) |
| Negative | 1 | 0 | 5 | 1275 | |||
| Total | 6 | 0 | 5 | 1276 | |||
| All | Positive | 12 | 0 | 0 | 3 | 92.3 (12/13)(64.0 - 99.8) | 99.8 (1630/1633)(99.5 - 100) |
| Negative | 1 | 0 | 5 | 1625 | |||
| Total | 13 | 0 | 5 | 1628 |
= Positive endocervical swab specimen result in the APTIMA COMBO 2 Assay Positive andocenical swab specimen result in the APTMA
GC Assay ++ = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
= Positive andocervical swab specimen result in the APTMA COMBO 2 Assay.Negative endocervical swab specimen result in the APT
GC Assay
= Negative endocervical swab specimen result in the APTIMA COMBO 2 Assay:Positive endocervical swab specimen result in the APT
GC Assay + -2-
Positive endocervical swab specimen result in the AFTIMA COMBO 2 Assay:Positive endocervical swab specimen result in the APTIM
GC Assay
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APTIMA Assay for Neisseria gonorrhoeae – Expanded Indication: ThinPrep Specimens
Table 5: Performance of the APTIMA GC Assay in PreservCyt Processed Liquid Pap
Specimens by Collection Site
| Site | APTIMA GCPreservCytResult | ++ | +/- | -/+ | -/- | Prev(%) | Sensitivity (%)(95% C.I.) | Specificity (%)(95% C.I.) | PPV(%) | NPV(%) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Positive | 5 | 0 | 0 | 0 | 5.0 | 100 (5/5)(47.8 - 100) | 100 (95/95)(96.2 - 100) | 100 | 100 |
| 1 | Negative | 0 | 0 | 0 | 95 | |||||
| Total | 5 | 0 | 0 | 95 | ||||||
| 2 | Positive | 1 | 0 | 0 | 0 | 0.8 | 100 (1/1)(2.5 - 100) | 100 (123/123)(97.0 - 100) | 100 | 100 |
| 2 | Negative | 0 | 0 | 0 | 123 | |||||
| Total | 1 | 0 | 0 | 123 | ||||||
| 3 | Positive | 4 | 0 | 0 | 0 | 1.1 | 80.0 (4/5)(28.4 - 99.5) | 100 (470/470)(99.2 - 100) | 100 | 99.8 |
| 3 | Negative | 1 | 0 | 0 | 470 | |||||
| Total | 5 | 0 | 0 | 470 | ||||||
| 4 | Positive | 1 | 0 | 0 | 3 | 0.3 | 100 (1/1)(2.5 - 100) | 99.0 (283/286)(97.0 - 99.8) | 25.0 | 100 |
| 4 | Negative | 0 | 0 | 3 | 280 | |||||
| Total | 1 | 0 | 3 | 283 | ||||||
| 5 | Positive | 0 | 0 | 0 | 0 | 0.0 | N/A | 100 (297/297)(98.8 - 100) | N/A | 100 |
| 5 | Negative | 0 | 0 | 0 | 297 | |||||
| Total | 0 | 0 | 0 | 297 | ||||||
| 6 | Positive | 1 | 0 | 0 | 0 | 0.3 | 100 (1/1)(2.5 - 100) | 100 (362/362)(99.0 - 100) | 100 | 100 |
| 6 | Negative | 0 | 0 | 2 | 360 | |||||
| Total | 1 | 0 | 2 | 360 | ||||||
| ALL | Positive | 12 | 0 | 0 | 3 | 0.8 | 92.3 (12/13)(64.0 - 99.8) | 99.8 (1630/1633)(99.5 - 100) | 80.0 | 99.9 |
| ALL | Negative | 1 | 0 | 5 | 1625 | |||||
| Total | 13 | 0 | 5 | 1628 |
N:/A = not applicable
= Positive endocerical swab specimen result in the APTMA COMBO 2 Assay:Positive endocenvical swab specimen result in the APTIMA GC
Assay +;++ Assay
= Postive endocervical swab specimen result in the APTMA COMBO 2 AssayNegative endocenvical swab specimen result in the AFTMA
GC Assey +) -GC Assay
= Negative endocervical swats specimen result in the APTIMA COMBO 2 Assay:Positive andocervical swab specimen result in the APTIMA
GC Assay - 14 GC Assay
Positive andocenvical swab speimen result in the AFT MA COMBO 2 AssayPositive endcoenics! strats specimen result in the AFTMA GC
Assoy - 5-Assay
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APTIMA Assay for Neisseria gonorrhoeae – Expanded Indication: ThinPrep Specimens
| fable 6: PreservCvt Liquid Pap Specimen Analysis for Patient Infected Status | ||||
|---|---|---|---|---|
| Patient Infected Status | Endocervical Swab | Symptom Status | ||
| APTIMACOMBO 2Assay | APTIMA GCAssay | Symptomatic | Asymptomatic | |
| Inconclusive | E | P | 0 | 1 |
| Infected | P | P | 7 | 6 |
| Non-Infected | N | N | 352 | 1276 |
| Non-Infected | N | P | 0 | 5 |
| Total | 359 | 1288 |
Prevalence
The prevalence of GC 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 GC in North America, for PreservCyt liquid Pap specimens on the APTIMA GC Assay is shown in Table 7
Table 7: Prevalence of N. gonorrhoeae by Clinical Site and Overall as Determined by APTIMA GC Assay Results Using PreservCyt Liquid Pap Specimens
| Site | % (#positive/#tested) |
|---|---|
| 1 | 5.0 (5/100) |
| 2 | 0.8 (1/124) |
| 3 | 0.8 (4/475) |
| 4 | 1.4 (4/287) |
| 5 | 0.0 (0/297) |
| 6 | 0.5 (2/364) |
| All | 1.0 (16/1647) |
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APTIMA Assay for Neisseria gonorrhoeae -- Expanded Indication: ThinPrep Specimens
Conclusions from Non-Clinical and Clinical Data
The non-clinical and clinical study results support the use of PreservCyt liquid Pap specimens collected and processed by the Cytyc ThinPrep 2000 Processor in the currently marketed GEN-PROBE APTIMA Assay for Neisseria gonorrhoeae. The currently marketed GEN-PROBE APTIMA Specimen Transfer Kit provides necessary materials and instructions to allow for the testing of PreservCyt liquid Pap specimens in the APTIMA GC Assay.
The results of the clinical study demonstrate reasonable evidence that when the APTIMA GC Assay and the APTIMA Specimen Transfer Kit are labeled as proposed, the APTIMA GC Assay continues to be safe and effective for its stated intended use.
Contraindications and Cautions
There are no contraindications or cautions.
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Image /page/13/Picture/1 description: The image shows the seal of the Department of Health & Human Services (USA). The seal features an abstract design of an eagle with outstretched wings, symbolizing protection and care. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the emblem.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV - 7 2006
Mr. E. Joseph McMullen Associate Director, Regulatory Affairs Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121
Re: K062440
Trade/Device Name: GEN-PROBE® APTIMA® Assay for Neisseria gonorrhoeae Regulation Number: 21 CFR 866.3390 Regulation Name: Neisseria spp. direct serological test reagents Regulatory Class: Class II Product Code: LSL Dated: August 18, 2006 Received: August 21, 2006
Dear Mr. McMullen:
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).
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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 (240)276-0450. 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,
Sally anton
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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APTIMA Assay® for Neisseria gonorrhoege
INDICATIONS FOR USE STATEMENT
510(k) Number: (if known)
GEN-PROBE APTIMA Assay® for Neisseria gonorrhoeae Device Name: Indications for Use:
The APTIMA® Assay for Neisseria gonorrhoeae is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC) to aid in the diagnosis of gonococcal urogenital disease. The assay may be used to test the following specimens from symptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; and female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: cliniciancollected endocervical and vaginal swab specimens; and patient-collected vaginal swab specimens and female and male urine specimens. The assay is also intended for use with the testing of gynecological specimens, from both symptomatic and asymptomatic patients, collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System.
4 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.
Prescription Use X (Part 21 CFR 801 Subpart D) OR
Over-the-Counter Use (Part 21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANQTHER PAGE IF NEEDED
Concurrence of CDRH, Office of Device Evaluation (QDE)
Tarana
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K062440
§ 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).