(350 days)
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 RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease using the PANTHER System as specified.
On the PANTHER System, the assay may be used to test the following specimens from symptomatic and asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt Solution, and patient-collected vaginal swab specimens.
The APTIMA Combo 2 Assay combines the technologies of target capture, TMA, and DKA. Specimens are collected and transferred into their respective specimen transport tubes. The transport solutions in these tubes release the rRNA targets and protect them from degradation during storage. When the APTIMA Combo 2 Assay is performed in the laboratory, the target rRNA molecules are isolated from specimens by use of capture oligomers via target capture that utilizes magnetic microparticles. The capture oligomers contain sequences complementary to specific regions of the target molecules as well as a string of deoxyadenosine residues. A separate capture oligomer is used for each target. During the hybridization step, the sequence specific regions of the capture oligomers bind to specific regions of the target molecules. The capture oligomer:target complex is then captured out of solution by decreasing the temperature of the reaction to room temperature. This temperature reduction allows hybridization to occur between the deoxyadenosine region on the capture oligomer and the poly-deoxythymidine molecules that are covalently attached to the magnetic particles. The microparticles, including the captured target molecules bound to them, are pulled to the side of the reaction vessel using magnets and the supernatant is aspirated. The particles are washed to remove residual specimen matrix that may contain amplification reaction inhibitors. After the target capture steps are completed, the specimens are ready for amplification. Target amplification assays are based on the ability of complementary oligonucleotide primers to specifically anneal and allow enzymatic amplification of the target nucleic acid strands. The APTIMA Combo 2 Assay replicates a specific region of the 23S rRNA from CT and a specific region of the 16S rRNA from GC via DNA intermediates. A unique set of primers is used for each target molecule. Detection of the rRNA amplification product sequences (amplicon) is achieved using nucleic acid hybridization. Single-stranded chemiluminescent DNA probes, which are complementary to a region of each target amplicon, are labeled with different acridinium ester molecules. The labeled DNA probes combine with amplicon to form stable RNA:DNA hybrids. The Selection Reagent differentiates hybridized from unhybridized probe, eliminating the generation of signal from unhybridized probe. During the detection step, light emitted from the labeled RNA:DNA hybrids is measured as photon signals in a luminometer, and are reported as Relative Light Units (RLU). In DKA, differences in the kinetic profiles of the CT and GC labeled probes allow for the differentiation of signal; kinetic profiles are derived from measurements of photon output during the detection read time. The chemiluminescent detection for CT signal has very rapid kinetics and has the "flasher" kinetic type. The chemiluminescent detection reaction for GC signal is relatively slower and has the "glower" kinetic type. Assay results are determined by a cut-off based on the total RLU and the kinetic curve type.
This FDA 510(k) summary describes the APTIMA Combo 2® Assay on the PANTHER System, a device for in vitro qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC). The submission is for clearing the assay for use on the PANTHER System, as it was previously cleared on the TIGRIS System.
Here's an analysis of the provided information:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for this device are implicitly tied to the performance characteristics, specifically sensitivity and specificity, as demonstrated in the clinical study. While explicit "acceptance criteria" values for sensitivity and specificity are not directly stated in the summary, the reported performance characteristics are presented with 95% confidence intervals, suggesting that the observed values met predefined thresholds for regulatory approval. The fact that the device received 510(k) clearance further indicates that its performance was deemed acceptable by the FDA.
Table of Performance for APTIMA Combo 2® Assay on the PANTHER System (Clinical Study Results)
| Specimen Type | Target | Reported Sensitivity % (95% CI) | Reported Specificity % (95% CI) |
|---|---|---|---|
| Male Urethral Swab | CT | 100 (96.3-100) | 99.1 (97.7-99.7) |
| Clinician-Collected/Patient-Collected Vaginal Swab | CT | 97.2 (92.1-99.0) | 98.5 (97.6-99.0) |
| PreservCyt Solution Liquid Pap | CT | 98.2 (93.8-99.5) | 100 (99.7-100) |
| Female Endocervical Swab | CT | 97.2 (92.1-99.0) | 99.3 (98.6-99.6) |
| Male Urethral Swab | GC | 100 (89.8-100) | 100 (99.3-100) |
| Vaginal Swab | GC | 97.7 (87.9-99.6) | 99.6 (99.0-99.8) |
| PreservCyt Solution Liquid Pap | GC | 100 (91.8-100) | 100 (99.7-100) |
| Female Endocervical Swab | GC | 100 (91.6-100) | 99.8 (99.4-100) |
Analytical Sensitivity (Limits of Detection):
- CT: Claimed 1 IFU/assay (7.25 IFU/swab, 9.75 IFU/mL, PreservCyt Solution liquid Pap). 100% positivity was observed in samples containing CT concentrations of 0.03 IFU/mL.
- GC: Claimed 50 cells/assay (362 cells/swab, 488 cells/mL PreservCyt Solution liquid Pap). 100% positivity was observed in samples containing GC concentrations of 0.04 CFU/mL.
Within Laboratory Precision (STM matrix, selected rows as an example):
| Target Concentration CT (IFU/mL) | GC (CFU/mL) | Agrmt (%) | Total SD (x1000) | Total CV (%) |
|---|---|---|---|---|
| 0 | 0 | 100 | 1.3 | 20.1 |
| 0.25 | 0 | 100 | 87.1 | 7.1 |
| 0 | 12.5 | 100 | 43.2 | 4.0 |
| 2.5 | 125 | 100 | 101.5 | 4.1 |
Carryover Study: Overall carryover rate was 0% with a 95% confidence interval of 0-0.1%. This meets an implicit acceptance criterion of negligible or acceptable carryover.
2. Sample Size Used for the Test Set and Data Provenance
The clinical study was a prospective, multicenter clinical study conducted across 7 geographically and ethnically diverse US clinical sites.
Test Set Sample Sizes:
- Male subjects: 580 enrolled, 567 evaluable male urethral swab samples.
- 18 male urethral swab specimens had final invalid results and were excluded.
- Female subjects: 1332 enrolled.
- 1319 evaluable vaginal swab samples (clinician-collected/patient-collected combined).
- 1330 evaluable PreservCyt Solution liquid Pap samples.
- 1310 evaluable endocervical swab samples.
- 1 vaginal swab and 1 endocervical swab had final CT equivocal results and were excluded.
- 1 PreservCyt and 1 endocervical swab had final GC equivocal results and were excluded.
- Female urine specimens were collected but used as part of the "infected status algorithm" (ground truth definition) rather than directly tested as a primary specimen type for performance against the APTIMA Combo 2 Assay on PANTHER for this 510(k).
Data Provenance: United States (7 US clinical sites). The study was prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The ground truth was established using an "infected status algorithm" based on results from two specimen types and two reference NAATs (Nucleic Acid Amplification Tests). The specific number and qualifications of experts directly involved in adjudicating the "infected status" or interpreting the reference NAATs are not explicitly stated in the provided text.
However, for a device like this, standard practice for establishing ground truth for NAATs in clinical trials typically involves:
- Use of one or more FDA-cleared and/or highly sensitive and specific reference NAATs.
- Concordance of positive results across multiple tests/specimens to define an "infected status."
- Discrepancies often resolved by a third, highly sensitive method or expert clinical review, though this detail is not provided.
The text states: "Subjects were categorized as infected if a positive result occurred in each of the 2 reference NAATs." This implies a rule-based algorithm for ground truth rather than individual expert adjudication for each case.
4. Adjudication Method for the Test Set
The adjudication method for determining the "infected status" (ground truth) was an algorithm-based approach:
- For male subjects and female subjects, if the positive NAAT results occurred only in the urine specimens and not in the PreservCyt specimens, the subject was categorized as infected; however, for the evaluation of the non-urine specimen types, the specimens were considered non-infected.
- "Subjects were categorized as infected if a positive result occurred in each of the 2 reference NAATs."
This indicates a 2-out-of-2 (or 2+0) concordance rule for positivity to establish infection status. The text doesn't mention a tie-breaking or expert review process if results were discordant between the two reference NAATs, but specimens with "invalid, equivocal, or error results" were retested, and those with final invalid/equivocal results were excluded from analysis.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done.
This device is an in vitro diagnostic test, specifically a nucleic acid amplification test (NAAT). These types of tests are designed to provide a qualitative result (positive/negative) based on an analytical assay run on an automated system, not to be interpreted by human readers in the same way an imaging device or pathology slide might be. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply to this type of device. The "AI" (algorithm) here is the test.
6. Standalone (Algorithm Only) Performance
Yes, standalone performance was done.
The entire clinical study described, including the sensitivity and specificity values provided in Tables 6, 7, 8, 9, 10, and 11, represents the standalone performance of the APTIMA Combo 2 Assay on the PANTHER System. The results are compared against an "infected status algorithm" which serves as the ground truth, not against human interpretation of raw assay data. The device's output is the final diagnostic result.
7. Type of Ground Truth Used
The ground truth used was an algorithm-based "infected status" derived from the results of two reference nucleic acid amplification tests (NAATs) on two different specimen types (e.g., male urethral swab and male urine for males, and PreservCyt and urine for females).
Specifically:
- "Male urethral swab, male and female urine, and PreservCyt samples were tested with cleared nucleic acid amplification tests (NAATs) to establish the infected status."
- "The infected status algorithm used results from two specimen types and two reference NAATs. Subjects were categorized as infected if a positive result occurred in each of the 2 reference NAATs."
- "For female subjects, if the positive NAAT results occurred only in the urine specimens and not in the PreservCyt specimens, the subject was categorized as infected; however, for the evaluation of the non-urine specimen types, the specimens were considered non-infected."
8. Sample Size for the Training Set
The provided text does not specify a sample size for a training set. This document is a 510(k) summary for a diagnostic test, not a submission for a de novo machine learning algorithm that typically requires a distinct training and test set with explicit disclosure of training data. The "device" in this context is the analytical assay and automated system. While the assay itself (APTIMA Combo 2) was developed and validated, the data tables presented relate to the performance evaluation (test set) for the new platform (PANTHER System).
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is detailed for the purpose of a machine learning algorithm in this 510(k) summary, the process for establishing ground truth for a training set is not applicable here. The provided data focuses on the validation of the device on a new platform (PANTHER System) for regulatory clearance, where the clinical study (test set) is the primary evidence for performance.
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Gen-Probe Incorporated
510(k) SUMMARY
MAY - 3 2012
APTIMA Combo 2® Assay on the PANTHER System
Sponsor/Contact Information
Submitted By:
Name: Address: Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121 (858) 410-8000
Company Contact:
Jody J. Fleming Contact: Regulatory Affairs Manager Phone: 858-410-8634 Fax: 858-410-7876 Email: jody.fleming@gen-probe.com
Date Prepared:
May 1, 2012
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General Information
| Trade Name: | APTIMA Combo 2® Assay |
|---|---|
| Common or Usual Name: | Ribosomal RNA (rRNA) target-amplified nucleic acid probetest for the in vitro diagnostic detection of Chlamydiatrachomatis and/or Neisseria gonorrhoeae |
| Classification Names: | DNA Probe, Nucleic Acid Amplification, ChlamydiaDNA Reagents, Neisseria |
APTIMA Combo 2 Assay
| Device Description | DNA Probe, Nucleic Acid Amplification, Chlamydia |
|---|---|
| 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; K032194
This pre-market application is to clear the APTIMA Combo 2 Assay for use on the PANTHER System. The APTIMA Combo 2 Assay was cleared on the predicate TIGRIS System on December 24, 2003 (K032194). Clearance of this 510(k) will add the PANTHER System as an optional platform. No changes were introduced to the APTIMA Combo 2 Assay reagents.
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Device Description
The APTIMA Combo 2 Assay combines the technologies of target capture, TMA, and DKA.
Specimens are collected and transferred into their respective specimen transport tubes. The transport solutions in these tubes release the rRNA targets and protect them from degradation during storage. When the APTIMA Combo 2 Assay is performed in the laboratory, the farget rRNA molecules are isolated from specimens by use of capture oligomers via target capture that utilizes magnetic microparticles. The capture oligomers contain sequences complementary to specific regions of the target molecules as well as a string of deoxyadenosine residues. A separate capture oligomer is used for each target. During the hybridization step, the sequence specific regions of the capture oligomers bind to specific regions of the target molecules. The capture oligomer:target complex is then captured out of solution by decreasing the temperature of the reaction to room temperature. This temperature reduction allows hybridization to occur between the deoxyadenosine region on the capture oligomer and the poly-deoxythymidine molecules that are covalently attached to the magnetic particles. The microparticles, including the captured target molecules bound to them, are pulled to the side of the reaction vessel using magnets and the supernatant is aspirated. The particles are washed to remove residual specimen matrix that may contain amplification reaction inhibitors. After the target capture steps are completed, the specimens are ready for amplification.
Target amplification assays are based on the ability of complementary oligonucleotide primers to specifically anneal and allow enzymatic amplification of the target nucleic acid strands. The APTIMA Combo 2 Assay replicates a specific region of the 23S rRNA from CT and a specific region of the 16S rRNA from GC via DNA intermediates. A unique set of primers is used for each target molecule. Detection of the rRNA amplification product sequences (amplicon) is achieved using nucleic acid hybridization. Single-stranded chemiluminescent DNA probes, which are complementary to a region of each target amplicon, are labeled with different acridinium ester molecules. The labeled DNA probes combine with amplicon to form stable RNA:DNA hybrids. The Selection Reagent differentiates hybridized from unhybridized probe, eliminating the generation of signal from unhybridized probe. During the detection step, light emitted from the labeled RNA:DNA hybrids is measured as photon signals in a luminometer,
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and are reported as Relative Light Units (RLU). In DKA, differences in the kinetic profiles of the CT and GC labeled probes allow for the differentiation of signal; kinetic profiles are derived from measurements of photon output during the detection read time. The chemiluminescent detection for CT signal has very rapid kinetics and has the "flasher" kinetic type. The chemiluminescent detection reaction for GC signal is relatively slower and has the "glower" kinetic type. Assay results are determined by a cut-off based on the total RLU and the kinetic curve type.
Intended Use
The AC2 Assay intended use is stated below.
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 RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease using the PANTHER System as specified.
On the PANTHER System, the assay may be used to test the following specimens from symptomatic and asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt Solution, and patient-collected vaginal swab specimens'.
'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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Comparison to Predicate
: ·
· A comparison of the AC2 Assay on the PANTHER System with the predicate TIGRIS System is summarized below.
| Item | AC2 on TIGRIS System(Predicate Device) | AC2 on PANTHER System |
|---|---|---|
| Device Class | II | II |
| Regulation Specialty | Microbiology | Microbiology |
| Qualitative /QuantitativeAssay | Qualitative | Qualitative |
| Function | Detection and differentiation ofrRNA from Chlamydiatrachomatis and Neisseriagonorrhoeae | Detection and differentiation ofrRNA from Chlamydiatrachomatis and Neisseriagonorrhoeae |
| Indications For Use /Intended Use | Detection and differentiation ofrRNA from Chlamydiatrachomatis and Neisseriagonorrhoeae on the DTS andTIGRIS Systems. | Detection and differentiation ofrRNA from Chlamydiatrachomatis and Neisseriagonorrhoeae on the PANTHERSystem. |
| Specimen Types | Female specimens:• Vaginal swab• Endocervical swab• ThinPrep in PreservCytsolution• UrineMale Specimens:• Urethral Swab | Female specimens:• Vaginal swab• Endocervical swab• ThinPrep in PreservCytsolutionMale Specimens:• Urethral Swab |
| Item | AC2 on TIGRIS System(Predicate Device) | AC2 on PANTHER System |
| Swabs:After collection, transport andstore swab in transport tube at 2-30°C and test within 60 days. Iflonger storage is desired, freeze at-20°C to -70°C for up to 365days. | Swabs:After collection, transport andstore swab in transport tube at 2-30°C and test within 60 days. Iflonger storage is desired, freeze at-20°C to -70°C for up to 365days. | |
| SpecimenTransport/Storage | ThinPrep Liquid Pap inPreservCyt:Transport and store in PreservCytsolution at 2-30°C for up to 30days. After transfer to APTIMAspecimen transfer tube, store at15-30°C for 14 days or store at2-8°C for 30 days. If longerstorage is desired, freeze at -20°Cto -70°C for up to 365 days.Urine:After collection, transfer urine totransport tube within 24 hoursand store at 2-30°C; Must beassayed within 30 days aftertransfer. If held longer, freeze -at-20°C to -70°C for up to 365 days. | ThinPrep Liquid Pap inPreservCyt:Transport and store in PreservCytsolution at 2-30°C for up to 30days. After transfer to APTIMAspecimen transfer tube, store at15-30°C for 14 days or store at2-8°C for 30 days. If longerstorage is desired, freeze at -20°Cto -70°C for up to 365 days. |
| Type of Assay | Nucleic Acid Amplification Test | Nucleic Acid Amplification Test |
| Technology* | Target Capture (TC),Transcription-MediatedAmplification (TMA),Hybridization Protection Assay .(HPA) | Target Capture (TC),Transcription-MediatedAmplification (TMA),Hybridization Protection Assay(HPA) |
| Detection Format | HPA which provides relativelight units (RLUs) that areassessed against an establishedassay cutoff | HPA which provides relative lightunits (RLUs) that are assessedagainst an established assaycutoff |
Comparison to Predicate Device
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*A number of Gen-Probe APTIMA assays (that are based on TC, TMA, and HPA technologics) have been cleared by FDA including: the AC2 Assay (K060652), the APTIMA CT Assay (K061413) and the APTIMA GC Assay (K061509) for use on the automated TIGRIS System and the semiautomated DTS Systems.
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Performance Data
Brief Description of Non-Clinical Data
The following studies were conducted to support analytical performance of the PANTHER System.
Analytical Sensitivity Study
Chlamydia trachomatis analytical sensitivity (limits of detection) was determined by directly comparing dilutions of CT organisms in the APTIMA COMBO 2 assay. The analytical sensitivity claim for the assay is 1 IFU/assay (7.25 IFU/swab, 9.75 IFU/mL, PreservCyt Solution liquid Pap). However, dilutions of less than 1 IFU/assay tested positive in the APTIMA COMBO 2 Assay (for this study, 100% positivity was observed in samples containing CT concentrations of 0.03 IFU/mL).
Neisseria gonorrhoeae analytical sensitivity (limits of detection) was determined by directly comparing dilutions of GC organismsin the APTIMA COMBO 2 Assay. The analytical sensitivity claim for the assay is 50 cells/assay (362 cells/swab, 488 cells/mL PreservCyt Solution liquid Pap). However, dilutions of less than 50 cells/assay tested positive in the APTIMA COMBO 2 Assay (for this study, 100% positivity was observed in samples containing GC concentrations of 0.04 CFU/mL).
Within Laboratory Precision Study
APTIMA COMBO 2 Assay precision was evaluated at Gen-Probe using the PANTHER System. Testing was performed using three PANTHER Systems and three lots of assay reagents. Testing was performed over 24 days.
Reproducibility panel members were created using negative PreservCyt Solution liquid Pap specimens and STM. The positive panel members were created by spiking CT and/or GC organisms to the targeted concentrations shown in Table 1.
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.
.
For each panel member, Table 1 presents mean RLU, between-instrument, between-lot, between-run, within-run, and overall variation as SD and percent CV. Percent agreement with expected results is also shown.
Page 8 of 26
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Table 1. PANTHER System Within Laboratory Precision Data
| Target Concentration | Mean | BetweenInstruments | BetweenLots | BetweenRuns | WithinRuns | Total | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Matrix | CT(IFU/mL) | GC(CFU/mL) | Agreed/N | Agrmt(%) | RLU(x1000) | SD(x1000) | CV(%) | SD(x1000) | CV(%) | SD(x1000) | CV(%) | SD(x1000) | CV(%) | SD(x1000) | CV(%) |
| STM | 0 | 0 | 96/96 | 100 | 6 | 0.1 | 1.0 | 0.9 | 13.5 | 0.0 | 0.0 | 1.0 | 15.7 | 1.3 | 20.1 |
| 0.25 | 0 | 95/95 | 100 | 1226 | 70.0 | 5.7 | 20.0 | 1.6 | 8.4 | 0.7 | 47.1 | 3.8 | 87.1 | 7.1 | |
| 2.5 | 0 | 96/96 | 100 | 1249 | 78.0 | 6.2 | 6.1 | 0.5 | 0.0 | 0.0 | 32.9 | 2.6 | 84.8 | 6.8 | |
| 25 | 0 | 95/95 | 100 | 1268 | 72.9 | 5.7 | 15.3 | 1.2 | 0.0 | 0.0 | 39.6 | 3.1 | 84.3 | 6.6 | |
| 0 | 12.5 | 96/96 | 100 | 1081 | 18.4 | 1.7 | 28.6 | 2.6 | 0.0 | 0.0 | 26.7 | 2.5 | 43.2 | 4.0 | |
| 0 | 125 | 96/96 | 100 | 1266 | 29.8 | 2.4 | 0.0 | 0.0 | 8.9 | 0.7 | 27.6 | 2.2 | 41.6 | 3.3 | |
| 0 | 1250 | 96/96 | 100 | 1309 | 29.4 | 2.2 | 0.0 | 0.0 | 9.8 | 0.8 | 31.8 | 2.4 | 44.4 | 3.4 | |
| 2.5 | 125 | 96/96 | 100 | 2456 | 86.6 | 3.5 | 0.0 | 0.0 | 0.0 | 0.0 | 53.0 | 2.2 | 101.5 | 4.1 | |
| 2.5 | 2500 | 96/96 | 100 | 2509 | 73.1 | 2.9 | 0.0 | 0.0 | 19.8 | 0.8 | 46.8 | 1.9 | 89.0 | 3.5 | |
| 1000 | 2500 | 96/96 | 100 | 2496 | 31.7 | 1.3 | 6.1 | 0.2 | 0.0 | 0.0 | 193.7 | 7.8 | 196.3 | 7.9 | |
| 1000 | 125 | 96/96 | 100 | 2471 | 83.6 | 3.4 | 9.4 | 0.4 | 0.0 | 0.0 | 52.4 | 2.1 | 99.1 | 4.0 | |
| PCyt | 0 | 0 | 96/96 | 100 | 7 | 0.0 | 0.0 | 0.8 | 11.7 | 0.0 | 0.0 | 1.5 | 22.4 | 1.7 | 24.7 |
| 0.25 | 0 | 96/96 | 100 | 1113 | 92.3 | 8.3 | 30.1 | 2.7 | 0.0 | 0.0 | 63.6 | 5.7 | 116.0 | 10.4 | |
| 2.5 | 0 | 96/96 | 100 | 1194 | 62.5 | 5.2 | 24.8 | 2.1 | 0.0 | 0.0 | 47.0 | 3.9 | 82.1 | 6.9 | |
| 25 | 0 | 95/95 | 100 | 1222 | 65.1 | 5.3 | 26.4 | 2.2 | 14.7 | 1.2 | 35.0 | 2.9 | 79.8 | 6.5 | |
| 0 | 12.5 | 93/93 | 100 | 994 | 33.3 | 3.3 | 36.9 | 3.7 | 16.0 | 1.6 | 26.2 | 2.6 | 58.4 | 5.9 | |
| 0 | 125 | 95/95 | 100 | 1189 | 40.1 | 3.4 | 4.5 | 0.4 | 10.9 | 0.9 | 21.4 | 1.8 | 47.0 | 4.0 | |
| 0 | 1250 | 95/95 | 100 | 1239 | 37.7 | 3.0 | 7.5 | 0.6 | 13.6 | 1.1 | 18.0 | 1.5 | 44.6 | 3.6 | |
| 2.5 | 125 | 95/95 | 100 | 2333 | 99.7 | 4.3 | 35.3 | 1.5 | 12.6 | 0.5 | 48.9 | 2.1 | 117.2 | 5.0 |
Agent = ageemen, CV = cellicient of variation, N = multion liggio = Pesserv, V.V = reblive light uni. 3D = standad deviation, STM = swab casport masjium.
Nee; Variability form some to reasonal the variability de to hose tures is very stall. Were this econs, the minimity so messeed with standed levision and 54.7 kset o ().
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Carryover Studies for the PANTHER System
A multi-run analytical study was conducted using spiked panels on three PANTHER Systems. Carryover was assessed using approximately 20% high titer GC samples dispersed between negative samples. The runs included clusters of high positive samples with clusters of negative samples as well as single high positives dispersed in a specific pattern within the run. High titer samples were made using GC rRNA spiked into STM to give a final concentration equivalent to 2.5 x 108 CFU/mL. Testing was carried out using 5 runs on cach of three PANTHER Systems. Carryover was calculated from a total of 2938 valid negative results. The overall carryover rate was 0% with a 95% confidence interval of 0-0.1%.
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Brief Description of Clinical Data
Prevalence
The prevalence of CT and GC in patient populations depends on risk factors such as age, gender, the presence or absence of symptoms, the type of clinic, and the sensitivity of the test used to detect infections. A summary of the prevalence of three CT and GC disease outcomes, as determined by the APTIMA COMBO 2 Assay on the PANTHER System in the clinical trial, is shown in Tables 2, 3, and 4 by specimen type and clinical site.
Table 2. Prevalence of CT+/GC- Infections as Determined by the APTIMA COMBO 2 Assay by Specimen Type and Clinical Site
| CT+/GC- Prevalence % (# positive/# tested with valid results) | ||||
|---|---|---|---|---|
| Site | Male UrethralSwab | Clinician-Collected/Patient-collectedVaginal Swab | PreservCyt | EndocervicalSwab |
| 1 | 0(-) | 9.9 (21/212) | 8.9 (20/225) | 10.4 (20/193) |
| 2 | 13.9 (28/202) | 8.3 (19/230) | 8.8 (21/239) | 8.2 (19/231) |
| 3 | 1.3 (1/76) | 2.7 (6/222) | 3.1 (7/226) | 2.7 (6/223) |
| 4 | 24.4 (33/135) | 11.7 (40/342) | 10.2 (35/342) | 11.3 (38/337) |
| 5 | 0(-) | 4.5 (1/22) | 4.8 (1/21) | 4.3 (1/23) |
| 6 | 21.5 (28/130) | 11.9 (13/109) | 8.7 (10/115) | 8.8 (10/114) |
| 7 | 16.7 (1/6) | 3.2 (5/157) | 2.5 (4/161) | 2.6 (4/152) |
| All | 16.6 (91/549) | 8.1 (105/1294) | 7.4 (98/1329) | 7.7 (98/1273) |
PreservCyt = PreservCyt Solution Liquid Pap
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:
| CT-/GC+ Prevalence % (# positive/# tested with valid results) | ||||
|---|---|---|---|---|
| Site | Male UrethralSwab | Clinician-Collected/Patient-collected VaginalSwab | PreservCyt | EndocervicalSwab |
| 1 | 0 ( - ) | 3.3 (7/212) | 2.7 (6/225) | 3.1 (6/193) |
| 2 | 5.9 (12/202) | 3.9 (9/230) | 4.6 (11/239) | 4.8 (11/231) |
| 3 | 1.3 (1/76) | 0.5 (1/222) | 0.4 (1/226) | 0.4 (1/223) |
| 4 | 1.5 (2/135) | 1.5 (5/342) | 1.5 (5/342) | 1.8 (6/337) |
| 5 | 0 ( - ) | 0.0 (0/22) | 0.0 (0/21) | 0.0 (0/23) |
| 6 | 5.4 (7/130) | 3.7 (4/109) | 1.7 (2/115) | 1.8 (2/114) |
| 7 | 0.0 (0/6) | 2.5 (4/157) | 2.5 (4/161) | 2.6 (4/152) |
| All | 4.0 (22/549) | 2.3 (30/1294) | 2.2 (29/1329) | 2.4 (30/1273) |
Table 3. Prevalence of CT-/GC+ Infections as Determined by the APTIMA COMBO 2 Assay by Specimen Type and Clinical Site
PreservCyt = PreservCyt Solution Liquid Pap
Table 4. Prevalence of CT+/GC+ Infections as Determined by the APTIMA COMBO 2 Assay by Specimen Type and Clinical Site
| Site | Male UrethralSwab | CT+/GC+ Prevalence % (# positive/# tested with valid results)Clinician-Collected/Patient-collected VaginalSwab | PreservCyt | EndocervicalSwab |
|---|---|---|---|---|
| 2 | 3.0 (6/202) | 1.3 (3/230) | 0.8 (2/239) | 0.9 (2/231) |
| 3 | 0.0 (0/76) | 0.0 (0/222) | 0.0 (0/226) | 0.0 (0/223) |
| 4 | 4.4 (6/135) | 1.2 (4/342) | 0.9 (3/342) | 0.9 (3/337) |
| 5 | 0 (-) | 0.0 (0/22) | 0.0 (0/21) | 0.0 (0/23) |
| 6 | 0.8 (1/130) | 0.9 (1/109) | 0.9 (1/115) | 0.9 (1/114) |
| 7 | 0.0 (0/6) | 0.6 (1/157) | 0.6 (1/161) | 0.7 (1/152) |
| All | 2.4 (13/549) | 1.3 (17/1294) | 1.1 (14/1329) | 1.1 (14/1273) |
PreservCyt = PreservCyt Solution Liquid Pap
{12}------------------------------------------------
Positive and Negative Predictive Values for Hypothetical Prevalence Rates
The estimated positive and negative predictive values (PPV and NPV) of the APTIMA COMBO 2 Assay for different hypothetical prevalence rates are shown for each specimen type in Table 5. The PPV and NPV are derived for different hypothetical prevalence rates using the sensitivity and specificity estimates for each specimen type from the clinical performance study (see Table 6 and Table 9).
| Specimen Type | HypotheticalPrevalence (%) | CT Detection | GC Detection | ||
|---|---|---|---|---|---|
| PPV (%) | NPV (%) | PPV (%) | NPV (%) | ||
| Male UrethralSwab | 1 | 53.1 | 100 | 100 | 100 |
| 2 | 69.6 | 100 | 100 | 100 | |
| 5 | 85.5 | 100 | 100 | 100 | |
| 10 | 92.6 | 100 | 100 | 100 | |
| 15 | 95.2 | 100 | 100 | 100 | |
| 20 | 96.6 | 100 | 100 | 100 | |
| 25 | 97.4 | 100 | 100 | 100 | |
| Clinician-Collected VaginalSwab/Patient-CollectedVaginal Swab | 1 | 38.9 | 100 | 70.6 | 100 |
| 2 | 56.3 | 99.9 | 82.9 | 100 | |
| 5 | 76.8 | 99.9 | 92.6 | 99.9 | |
| 10 | 87.5 | 99.7 | 96.3 | 99.7 | |
| 15 | 91.7 | 99.5 | 97.7 | 99.6 | |
| 20 | 94.0 | 99.3 | 98.3 | 99.4 | |
| 25 | 95.5 | 99.1 | 98.8 | 99.2 | |
| PreservCytSolution LiquidPap | 1 | 100 | 100 | 100 | 100 |
| 2 | 100 | 100 | 100 | 100 | |
| 5 | 100 | 99.9 | 100 | 100 | |
| 10 | 100 | 99.8 | 100 | 100 | |
| 15 | 100 | 99.7 | 100 | 100 | |
| 20 | 100 | 99.6 | 100 | 100 | |
| 25 | 100 | 99.4 | 100 | 100 | |
| EndocervicalSwab | 1 | 58.5 | 100 | 85.8 | 100 |
| 2 | 74.0 | 99.9 | 92.4 | 100 | |
| 5 | 88.0 | 99.9 | 96.9 | 100 | |
| 10 | 93.9 | 99.7 | 98.5 | 100 | |
| 15 | 96.1 | 99.5 | 99.1 | 100 | |
| 20 | 97.2 | 99.3 | 99.3 | 100 | |
| 25 | 97.9 | 99.1 | 99.5 | 100 |
Table 5. Positive and Negative Predictive Values for Hypothetical Prevalence Rates by Specimen Type
{13}------------------------------------------------
Clinical Study Results
A prospective, multicenter clinical study was conducted to establish the performance characteristics of the APTIMA COMBO 2 Assay on the PANTHER System. Specimens were collected from symptomatic and asymptomatic men (n=580) and women (n=1332) enrolled from 7 geographically and ethnically diverse US clinical sites, including obstetrics and gynecology, family planning, public health, and STD clinics. Subjects were classified as symptomatic if symptoms were reported by the subject. Subjects were classified as asymptomatic if the subject did not report symptoms. Of the 580 male subjects, none were <18 years of age, 72 were 18 to 20 years of age, 201 were 21 to 25 years of age, and 307 were >25 years of age. Of the 1332 female subjects, 11 were 14 to 15 years of age, 59 were 16 to 17 years of age, 319 were 18 to 20 years of age, 401 were 21 to 25 years of age, and 542 were >25 years of age.
Up to 2 specimens were collected from each male subject (1 urethral swab and 1 first-catch urine, in that order) and up to 4 specimens were collected from each female subject (1 first-catch urine, 1 vaginal swab, 1 PreservCyt Solution liquid Pap specimen, and 1 endocervical swab, in that order). All specimens were clinician-collected except urine specimens and approximately half of the vaginal swab specimens, which were collected by the subject at the clinic. Approximately half of the PreservCyt Solution liquid Pap specimens were collected with a broom-type device and half were collected with a spatula and cytobrush. Samples were prepared for APTIMA testing in accordance with the appropriate APTIMA specimen collection kit package insert instructions.
All evaluable samples (567 male urethral swab, 1319 vaginal swab, 1330 PreservCyt, and 1310 endocervical swab samples) were tested with the APTIMA COMBO 2 Assay on the PANTHER System in accordance with package insert instructions. The samples were split amongst three laboratories (two external laboratories and GEN-PROBE). Samples with initial invalid, equivocal, or error results were retested. Eighteen (18) male urethral swab, 25 vaginal swab, 1 PreservCyt, and 37 endocervical swab specimens had final invalid results and were excluded from the analyses. Most of the invalid results were due to insufficient sample volume. One vaginal swab and 1 endocervical swab had final CT equivocal results and 1 PreservCyt and 1 endocervical swab had final GC equivocal results and were excluded from the analyses.
{14}------------------------------------------------
Male urethral swab, male and female urine, and PreservCyt samples were tested with cleared nucleic acid amplification tests (NAATs) to establish the infected status. The infected status algorithm used results from two specimen types and two reference NAATs. Subjects were categorized as infected if a positive result occurred in each of the 2 reference NAATs. For female subjects, if the positive NAAT results occurred only in the urine specimens and not in the PreservCyt specimens, the subject was categorized as infected; however, for the evaluation of the non-urine specimen types, the specimens were considered non-infected. Subjects that could not be categorized as infected or not infected were excluded from the performance analyses.
Chlamydia trachomatis Performance Results
Performance characteristics of the APTIMA COMBO 2 Assay were estimated by comparing PANTHER System results to the infected status algorithm. Table 6 shows the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the APTIMA COMBO 2 Assay for CT detection and the prevalence of CT (based on the infected status) in each specimen type.
| SpecType | n | TP | FP | TN | FN | Prev % | Sensitivity %(95% CI)¹ | Specificity %(95% CI)¹ | PPV %(95% CI)² | NPV %(95% CI)² |
|---|---|---|---|---|---|---|---|---|---|---|
| MS | 549 | 100 | 4 | 445 | 0 | 18.2 | 100(96.3-100) | 99.1(97.7-99.7) | 96.2(90.8-98.9) | 100(99.2-100) |
| CVS/PVS | 1274 | 104 | 18 | 1149 | 3 | 8.4 | 97.2(92.1-99.0) | 98.5(97.6-99.0) | 85.2(78.8-90.5) | 99.7(99.3-99.9) |
| PCyt | 1311 | 112 | 0 | 1197 | 2 | 8.7 | 98.2(93.8-99.5) | 100(99.7-100) | 100(96.9-100) | 99.8(99.4-100) |
| FS | 1254 | 104 | 8 | 1139 | 3 | 8.5 | 97.2(92.1-99.0) | 99.3(98.6-99.6) | 92.9(87.1-96.7) | 99.7(99.3-99.9) |
Table 6. Performance Characteristics of the APTIMA COMBO 2 Assay for CT Detection
CI = confidence interval, CVS = clinician-collected vaginal swab, FN = false negative, FP = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value. PCyt = PreservCyt Solution liquid Pap, PV = positive predictive value, Prev = prevalent-collected vaginal swab, Spec = specimen, TN = true negative. TY = true positive.
' Score Cl
2 PPV 95% CI computed from the exact 95% CI for the positive likelihood ratio, NPV 95% CI computed from the exact 95% CI from the negative likelihood ratio.
Table 7 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for CT detection and the prevalence of CT (based on the infected status) in each specimen type by symptom status. CT prevalence was higher in symptomatic men and women.
{15}------------------------------------------------
| SpecType | SxStatus | n | TP | FP | TN | FN | Prev% | Sensitivity%(95% CI)¹ | Specificity%(95% CI)¹ | PPV %(95% CI)² | NPV %(95% CI)² |
|---|---|---|---|---|---|---|---|---|---|---|---|
| MS | Sym | 238 | 59 | 1 | 178 | 0 | 24.8 | 100(93.9-100) | 99.4(96.9-99.9) | 98.3(91.5-100) | 100(98.0-100) |
| Asym | 311 | 41 | 3 | 267 | 0 | 13.2 | 100(91.4-100) | 98.9(96.8-99.6) | 93.2(82.5-98.5) | 100(98.7-100) | |
| CVS/PVS | Sym | 810 | 73 | 8 | 729 | 0 | 9.0 | 100(95.0-100) | 98.9(97.9-99.4) | 90.1(82.3-95.5) | 100(99.5-100) |
| Asym | 464 | 31 | 10 | 420 | 3 | 7.3 | 91.2(77.0-97.0) | 97.7(95.8-98.7) | 75.6(63.1-86.2) | 99.3(98.1-99.8) | |
| PCyt | Sym | 838 | 76 | 0 | 762 | 0 | 9.1 | 100(95.2-100) | 100(99.5-100) | 100(95.4-100) | 100(99.5-100) |
| Asym | 473 | 36 | 0 | 435 | 2 | 8.0 | 94.7(82.7-98.5) | 100(99.1-100) | 100(91.1-100) | 99.5(98.5-99.9) | |
| FS | Sym | 794 | 71 | 5 | 718 | 0 | 8.9 | 100(94.9-100) | 99.3(98.4-99.7) | 93.4(85.9-97.8) | 100(99.5-100) |
| Asym | 460 | 33 | 3 | 421 | 3 | 7.8 | 91.7(78.2-97.1) | 99.3(97.9-99.8) | 91.7(79.9-98.0) | 99.3(98.1-99.8) |
Table 7. Performance Characteristics of the APTIMA COMBO 2 Assay for CT Detection by Symptom Status
Asym = asymplomatic, CI = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urettral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PV = positive predictive value, Prev = prevalent-collected vaginal swab, Spec = specimen, Sx = symplom, Sym = symplomatic, TN = true negative, TP = true positive.
l Score Cl
2 PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the negative likelihood ratio.
Table 8 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for CT detection and the prevalence of CT (based on the infected status) in each specimen type by clinical site. CT prevalence varied across clinical sites, as expected.
{16}------------------------------------------------
| Table 8. Performance Characteristics of the APTIMA COMBO 2 Assay for CT Detection by | ||
|---|---|---|
| Clinical Site |
| SpecType | Site | n | TP | FP | TN | FN | Prev% | Sensitivity %(95% CI)¹ | Specificity %(95% CI)¹ | PPV %(95% CI)² | NPV %(95% CI)² |
|---|---|---|---|---|---|---|---|---|---|---|---|
| MS | 1 | 0 | 0 | 0 | 0 | 0 | NC | NC | NC | NC | NC |
| 2 | 202 | 34 | 0 | 168 | 0 | 16.8 | 100(89.8-100) | 100(97.8-100) | 100(90.3-100) | 100(98.0-100) | |
| 3 | 76 | 0 | 1 | 75 | 0 | 0.0 | NC | 98.7(92.9-99.8) | 0.0(NC) | 100(NC) | |
| 4 | 135 | 36 | 3 | 96 | 0 | 26.7 | 100(90.4-100) | 97.0(91.5-99.0) | 92.3(80.9-98.3) | 100(96.6-100) | |
| 5 | 0 | 0 | 0 | 0 | 0 | NC | NC | NC | NC | NC | |
| 6 | 130 | 29 | 0 | 101 | 0 | 22.3 | 100(88.3-100) | 100(96.3-100) | 100(88.9-100) | 100(96.7-100) | |
| 7 | 6 | 1 | 0 | 5 | 0 | 16.7 | 100(20.7-100) | 100(56.6-100) | 100(6.9-100) | 100(80.4-100) | |
| CVS/PVS | 1 | 211 | 23 | 6 | 182 | 0 | 10.9 | 100(85.7-100) | 96.8(93.2-98.5) | 79.3(64.2-91.2) | 100(98.2-100) |
| 2 | 230 | 18 | 4 | 206 | 2 | 8.7 | 90.0(69.9-97.2) | 98.1(95.2-99.3) | 81.8(64.7-93.9) | 99.0(97.1-99.9) | |
| 3 | 213 | 6 | 0 | 206 | 1 | 3.3 | 85.7(48.7-97.4) | 100(98.2-100) | 100(64.1-100) | 99.5(98.1-100) | |
| 4 | 335 | 40 | 4 | 291 | 0 | 11.9 | 100(91.2-100) | 98.6(96.6-99.5) | 90.9(79.8-97.3) | 100(98.8-100) | |
| 5 | 21 | 1 | 0 | 20 | 0 | 4.8 | 100(20.7-100) | 100(83.9-100) | 100(6.5-100) | 100(95.3-100) | |
| 6 | 107 | 11 | 3 | 93 | 0 | 10.3 | 100(74.1-100) | 96.9(91.2-98.9) | 78.6(56.4-94.6) | 100(96.8-100) | |
| 7 | 157 | 5 | 1 | 151 | 0 | 3.2 | 100(56.6-100) | 99.3(96.4-99.9) | 83.3(47.4-99.5) | 100(98.3-100) | |
| PCyt | 1 | 225 | 27 | 0 | 198 | 0 | 12.0 | 100(87.5-100) | 100(98.1-100) | 100(88.1-100) | 100(98.3-100) |
| 2 | 239 | 23 | 0 | 216 | 0 | 9.6 | 100(85.7-100) | 100(98.3-100) | 100(86.3-100) | 100(98.4-100) | |
| 3 | 217 | 7 | 0 | 210 | 0 | 3.2 | 100(64.6-100) | 100(98.2-100) | 100(65.7-100) | 100(98.7-100) | |
| 4 | 335 | 38 | 0 | 295 | 2 | 11.9 | 95.0(83.5-98.6) | 100(98.7-100) | 100(91.5-100) | 99.3(97.8-99.9) | |
| 5 | 21 | 1 | 0 | 20 | 0 | 4.8 | 100(20.7-100) | 100(83.9-100) | 100(6.5-100) | 100(95.3-100) | |
| 6 | 113 | 11 | 0 | 102 | 0 | 9.7 | 100(74.1-100) | 100(96.4-100) | 100(75.2-100) | 100(97.0-100) | |
| 7 | 161 | 5 | 0 | 156 | 0 | 3.1 | 100(56.6-100) | 100(97.6-100) | 100(57.8-100) | 100(98.4-100) |
Cl = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urethral swah, NPV = negative value, PCy1 = PreservCyt Solution liquid Pap, PPV = postive predictive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, TN = true negative, TP = true positive. ' Score Cl
2 PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the cract 95% Cl from the negative likelihood ratio.
{17}------------------------------------------------
| SpecType | Site | n | TP | FP | TN | FN | Prev % | Sensitivity %(95% CI)¹ | Specificity %(95% CI)¹ | PPV %(95% CI)² | NPV %(95% CI)² |
|---|---|---|---|---|---|---|---|---|---|---|---|
| FS | 1 | 193 | 24 | 3 | 166 | 0 | 12.4 | 100(86.2-100) | 98.2(94.9-99.4) | 88.9(73.6-97.5) | 100(98.0-100) |
| 2 | 231 | 19 | 2 | 209 | 1 | 8.7 | 95.0(76.4-99.1) | 99.1(96.6-99.7) | 90.5(73.4-98.6) | 99.5(97.7-100) | |
| 3 | 214 | 6 | 0 | 207 | 1 | 3.3 | 85.7(48.7-97.4) | 100(98.2-100) | 100(64.1-100) | 99.5(98.1-100) | |
| 4 | 330 | 39 | 2 | 288 | 1 | 12.1 | 97.5(87.1-99.6) | 99.3(97.5-99.8) | 95.1(84.8-99.3) | 99.7(98.2-100) | |
| 5 | 22 | 1 | 0 | 21 | 0 | 4.5 | 100(20.7-100) | 100(84.5-100) | 100(6.5-100) | 100(95.5-100) | |
| 6 | 112 | 11 | 0 | 101 | 0 | 9.8 | 100(74.1-100) | 100(96.3-100) | 100(75.2-100) | 100(97.0-100) | |
| 7 | 152 | 4 | 1 | 147 | 0 | 2.6 | 100(51.0-100) | 99.3(96.3-99.9) | 80.0(40.0-99.4) | 100(98.4-100) |
Table 8. Performance Characteristics of the APTIMA COMBO 2 Assay for CT Detection by Clinical Site (continued)
Cl = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PPV = positive predictive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, TN = true negative, TP = true positive. 1 Score Cl
2 YPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the exact 95% Cl from the negative likelihood ratio.
Table 9 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for GC detection and the prevalence of GC (based on the infected status) in each specimen type.
| SpecType | n | TP | FP | TN | FN | Prev% | Sensitivity %(95% CI)1 | Specificity %(95% CI)1 | PPV %(95% CI)2 | NPV %(95% CI)2 |
|---|---|---|---|---|---|---|---|---|---|---|
| MS | 546 | 34 | 0 | 512 | 0 | 6.2 | 100(89.8-100) | 100(99.3-100) | 100(90.2-100) | 100(99.3-100) |
| VS | 1258 | 42 | 5 | 1210 | 1 | 3.4 | 97.7(87.9-99.6) | 99.6(99.0-99.8) | 89.4(78.6-96.1) | 99.9(99.6-100) |
| PCyt | 1293 | 43 | 0 | 1250 | 0 | 3.3 | 100(91.8-100) | 100(99.7-100) | 100(92.1-100) | 100(99.7-100) |
| FS | 1238 | 42 | 2 | 1194 | 0 | 3.4 | 100(91.6-100) | 99.8(99.4-100) | 95.5(85.4-99.4) | 100(99.7-100) |
Table 9. Performance Characteristics of the APTIMA COMBO 2 Assay for GC Detection
Cl = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PV = positive predictive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, TN = true negative, TV = true positive.
Score CI
2 PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the exact 95% Cl from the negative likelihood ratio.
{18}------------------------------------------------
Table 10 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for GC detection and the prevalence of GC (based on the infected status) in each specimen type by symptom status. GC prevalence was higher in symptomatic men but similar in symptomatic and asymptomatic women.
Table 10. Performance Characteristics of the APTIMA COMBO 2 Assay for GC Detection by Symptom Status
| SpecType | SxStatus | n | TP | FP | TN | FN | Prev% | Sensitivity %(95% CI)¹ | Specificity %(95% CI)¹ | PPV %(95% CI)² | NPV %(95% CI)² |
|---|---|---|---|---|---|---|---|---|---|---|---|
| MS | Sym | 236 | 31 | 0 | 205 | 0 | 13.1 | 100(89.0-100) | 100(98.2-100) | 100(89.5-100) | 100(98.3-100) |
| MS | Asym | 310 | 3 | 0 | 307 | 0 | 1.0 | 100(43.9-100) | 100(98.8-100) | 100(44.4-100) | 100(99.3-100) |
| CVS/PVS | Sym | 802 | 27 | 4 | 771 | 0 | 3.4 | 100(87.5-100) | 99.5 (98.7-99.8) | 87.1(72.6-96.1) | 100(99.6-100) |
| CVS/PVS | Asym | 456 | 15 | 1 | 439 | 1 | 3.5 | 93.8(71.7-98.9) | 99.8 (98.7-100) | 93.8(74.0-99.8) | 99.8(98.9-100) |
| PCyt | Sym | 829 | 27 | 0 | 802 | 0 | 3.3 | 100(87.5-100) | 100(99.5-100) | 100(88.0-100) | 100(99.6-100) |
| PCyt | Asym | 464 | 16 | 0 | 448 | 0 | 3.4 | 100(80.6-100) | 100(99.1-100) | 100(81.3-100) | 100(99.3-100) |
| FS | Sym | 785 | 26 | 1 | 758 | 0 | 3.3 | 100(87.1-100) | 99.9(99.3-100) | 96.3(82.4-99.9) | 100(99.5-100) |
| FS | Asym | 453 | 16 | 1 | 436 | 0 | 3.5 | 100(80.6-100) | 99.8(98.7-100) | 94.1(74.3-99.8) | 100(99.3-100) |
| SpecType | Site | n | TP | FP | TN | FN | Prev% | Sensitivity %(95% CI)¹ | Specificity %(95% CI)¹ | PPV %(95% CI)² | NPV %(95% CI)² |
| MS | 1 | 0 | 0 | 0 | 0 | 0 | NC | NC | NC | NC | NC |
| 2 | 201 | 18 | 0 | 183 | 0 | 9.0 | 100(82.4-100) | 100(97.9-100) | 100(83.1-100) | 100(98.2-100) | |
| 3 | 76 | 1 | 0 | 75 | 0 | 1.3 | 100(20.7-100) | 100(95.1-100) | 100(6.4-100) | 100(98.7-100) | |
| 4 | 135 | 8 | 0 | 127 | 0 | 5.9 | 100(67.6-100) | 100(97.1-100) | 100(68.8-100) | 100(97.7-100) | |
| 5 | 0 | 0 | 0 | 0 | 0 | NC | NC | NC | NC | NC | |
| 6 | 128 | 7 | 0 | 121 | 0 | 5.5 | 100(64.6-100) | 100(96.9-100) | 100(65.8-100) | 100(97.7-100) | |
| 7 | 6 | 0 | 0 | 6 | 0 | 0.0 | NC | 100(61.0-100) | NC | 100( NC ) | |
| CVS/PVS | 1 | 207 | 13 | 2 | 192 | 0 | 6.3 | 100(77.2-100) | 99.0(96.3-99.7) | 86.7(64.6-98.3) | 100(98.4-100) |
| 2 | 230 | 12 | 0 | 217 | 1 | 5.7 | 92.3(66.7-98.6) | 100(98.3-100) | 100(77.8-100) | 99.5(97.9-100) | |
| 3 | 206 | 1 | 0 | 205 | 0 | 0.5 | 100(20.7-100) | 100(98.2-100) | 100(6.4-100) | 100(99.5-100) | |
| 4 | 331 | 8 | 1 | 322 | 0 | 2.4 | 100(67.6-100) | 99.7(98.3-99.9) | 88.9(59.1-99.7) | 100(99.1-100) | |
| 5 | 21 | 0 | 0 | 21 | 0 | 0.0 | NC | 100(84.5-100) | NC | 100( NC ) | |
| 6 | 106 | 3 | 2 | 101 | 0 | 2.8 | 100(43.9-100) | 98.1(93.2-99.5) | 60.0(24.6-92.8) | 100(98.0-100) | |
| 7 | 157 | 5 | 0 | 152 | 0 | 3.2 | 100(56.6-100) | 100(97.5-100) | 100(57.8-100) | 100(98.3-100) | |
| PCyt | 1 | 220 | 13 | 0 | 207 | 0 | 5.9 | 100(77.2-100) | 100(98.2-100) | 100(78.0-100) | 100(98.5-100) |
| 2 | 239 | 13 | 0 | 226 | 0 | 5.4 | 100(77.2-100) | 100(98.3-100) | 100(78.0-100) | 100(98.6-100) | |
| 3 | 210 | 1 | 0 | 209 | 0 | 0.5 | 100(20.7-100) | 100(98.2-100) | 100(6.4-100) | 100(99.5-100) | |
| 4 | 331 | 8 | 0 | 323 | 0 | 2.4 | 100(67.6-100) | 100(98.8-100) | 100(68.6-100) | 100(99.1-100) | |
| 5 | 21 | 0 | 0 | 21 | 0 | 0.0 | NC | 100(84.5-100) | NC | 100( NC ) | |
| 6 | 111 | 3 | 0 | 108 | 0 | 2.7 | 100(43.9-100) | 100(96.6-100) | 100(44.6-100) | 100(98.1-100) | |
| 7 | 161 | 5 | 0 | 156 | 0 | 3.1 | 100(56.6-100) | 100(97.6-100) | 100(57.8-100) | 100(98.4-100) | |
| SpecTypeFS | Site | n | TP | FP | TN | FN | Prev% | Sensitivity %(95% CI)¹ | Specificity %(95% CI)¹ | PPV %(95% CI)² | NPV %(95% CI)² |
| 1 | 1 | 189 | 12 | 1 | 176 | 0 | 6.3 | 100(75.8-100) | 99.4(96.9-99.9) | 92.3(68.6-99.8) | 100(98.2-100) |
| 2 | 2 | 231 | 13 | 0 | 218 | 0 | 5.6 | 100(77.2-100) | 100(98.3-100) | 100(78.0-100) | 100(98.5-100) |
| 3 | 3 | 207 | 1 | 0 | 206 | 0 | 0.5 | 100(20.7-100) | 100(98.2-100) | 100(6.4-100) | 100(99.5-100) |
| 4 | 4 | 327 | 8 | 1 | 318 | 0 | 2.4 | 100(67.6-100) | 99.7(98.2-99.9) | 88.9(59.1-99.7) | 100(99.1-100) |
| 5 | 5 | 22 | 0 | 0 | 22 | 0 | 0.0 | NC | 100(85.1-100) | NC | 100(NC) |
| 6 | 6 | 110 | 3 | 0 | 107 | 0 | 2.7 | 100(43.9-100) | 100(96.5-100) | 100(44.6-100) | 100(98.1-100) |
| 7 | 7 | 152 | 5 | 0 | 147 | 0 | 3.3 | 100(56.6-100) | 100(97.5-100) | 100(57.9-100) | 100(98.3-100) |
Asym = asymptomatic, CI = confidence interval, CVS = clinician-collected vaginal swab, FN = false negative, FP = false positive, FS = female endocervical swab, NPV = negative predictive value, PCy = PreservCyt Solution liquid Pap, PV = positive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, Sx = symptom, Sym = symptomatic, TN = true negative, TP = true positive.
Score Cl
2 PPV 95% CI computed from the exact 95% CI for the positive likelihood ratio, NPV 95% CI computed from the exact 95% CI from the negative likelihood ratio.
Table 11 shows the sensitivity, specificity, PPV, and NPV of the APTIMA COMBO 2 Assay for GC detection and the prevalence of GC (based on the infected status) in each specimen type by clinical site for the clinical performance study. GC prevalence varied across clinical sites, as expected.
{19}------------------------------------------------
Table 11. Performance Characteristics of the APTIMA COMBO 2 Assay for GC Detection by Clinical Site
Cl = confidence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PPV = positive predictive value, Prev = prevalent-collected vaginal swab, Spcc = specimen, TN = true negative, TV = true positive.
' Score CI
2 PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% Cl computed from the exact 95% Cl from the negative likelihood ratio.
{20}------------------------------------------------
Table 11. Performance Characteristics of the APTIMA COMBO 2 Assay for GC Detection by Clinical Site (continued)
CI = confidence interval, CVS = clinician-collected vaginal swab, FN = false negative, FP = false positive, FS = female endocervical swab, MS = male urethral swab, NPV = negative predictive value, PCyt = PreservCyt Solution liquid Pap, PPV = positive predictive value, Prev = prevalence, PVS = patient-collected vaginal swab, Spec = specimen, TN = 1rue negative, TV = true positive.
Score CI
2 PPV 95% Cl computed from the exact 95% CI for the positive likelihood ratio, NPV 95% CI computed from the exact 95% Cl from the negative likelihood ratio.
The frequency of test outcomes from reference NAAT and investigational PANTHER System testing is summarized in Table 13 for CT and in Tables 16 and Tables 16 and Table 15 for GC.
{21}------------------------------------------------
.
| Assay Results | |||||||
|---|---|---|---|---|---|---|---|
| AC2 DTS | ACT TIGRIS | AC2PANTHER | Symptom Status | ||||
| CT Infected Status | MS | MU | MS | MU | MS | Sym | Asym |
| Infected | + | + | + | + | + | 50 | 37 |
| Infected | + | + | + | + | NA | 4 | 1 |
| Infected | + | + | + | - | + | 2 | 0 |
| Infected | + | + | + | + | + | 4 | 2 |
| Infected | + | - | + | - | + | 3 | 2 |
| Not Infected | + | + | - | - | - | 0 | 1 |
| Not Infected | + | - | - | - | + | 0 | 1 |
| Not Infected | + | - | - | - | - | 1 | 1 |
| Not Infected | - | - | + | - | - | 3 | 2 |
| Not Infected | - | - | - | + | - | 1 | 1 |
| Not Infected | - | - | - | - | + | 1 | 2 |
| Not Infected | - | - | - | - | - | 173 | 262 |
| Not Infected | - | - | - | - | NA | 10 | 9 |
| Not Infected | NA | - | - | - | NA | 1 | 2 |
Table 12. CT Infected Status for Performance Evaluation in Male Urethral Swab Specimens
AC2 = APTIMA COMBO 2, ACT = APTIMA CT Assuy, Asym = asymptomatic, DTS = DTS Systems, MS = male urethral swab, MU = male urine, NA = result not available, PANTHER System, Sym = symptomatic, TIGRIS = TIGRIS DTS System
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:
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{22}------------------------------------------------
| Assay Results | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| CT InfectedStatus | AC2 TIGRIS | ACTTIGRIS | AC2PANTHER | Symptom Status | |||||
| PCyt | FU | PCyt | FU | CVS/PVS | PCyt | FS | Sym | Asym | |
| Infected | + | + | + | + | + | + | + | 62 | 26 |
| Infected | + | + | + | + | + | + | + | 0 | 1 |
| Infected | + | + | + | + | + | + | NA | 3 | 0 |
| Infected | + | + | + | + | + | + | + | 0 | 2 |
| Infected | + | + | + | + | + | + | + | 0 | 1 |
| Infected | + | + | + | + | NA | + | + | 1 | 1 |
| Infected | + | + | + | + | NA | + | NA | 2 | 1 |
| Infected | + | + | + | + | + | + | + | 4 | 1 |
| Infected | + | - | + | + | NA | + | NA | 0 | 1 |
| Infected | + | - | + | + | + | + | + | 4 | 0 |
| Infected | + | - | + | + | + | + | + | 0 | 1 |
| Infected | + | NA | + | NA | + | + | + | 0 | 1 |
| Infected | + | NA | + | NA | + | + | + | 0 | 1 |
| Infected | + | NA | + | NA | + | + | + | 0 | 1 |
| Infected¹ | - | + | - | + | + | - | + | 1 | 1 |
| Infected¹ | - | + | - | + | + | - | - | 2 | 0 |
| Infected¹ | - | + | - | + | + | - | + | 1 | 1 |
| Not Infected | + | - | - | - | - | - | + | 0 | 2 |
| Not Infected | - | + | - | - | - | - | + | 1 | 0 |
| Not Infected | - | - | + | - | + | - | + | 0 | 1 |
| Not Infected | - | - | + | - | + | - | - | 5 | 0 |
| Not Infected | - | - | - | + | + | - | + | 0 | 1 |
| Not Infected | - | - | - | + | + | - | NA | 0 | 1 |
| Not Infected | - | - | - | + | - | - | + | 1 | 3 |
| Not Infected | - | - | - | - | + | - | + | 1 | 0 |
| Not Infected | - | - | - | - | + | - | - | 2 | 7 |
| Not Infected | - | - | - | - | + | - | NA | 2 | 0 |
| Not Infected | - | - | - | - | + | - | + | 2 | 2 |
| Not Infected | - | - | - | - | + | - | - | 680 | 396 |
| Not Infected | - | - | - | - | - | - | NA | 29 | 8 |
| Not Infected | - | - | - | - | + | NA | - | 1 | 0 |
| Not Infected | - | - | - | - | NA | + | - | 17 | 4 |
| Not Infected | - | - | - | - | NA | - | NA | 8 | 1 |
| Not Infected | - | NA | - | - | - | - | - | 8 | 6 |
| Not Infected | - | NA | - | - | - | - | NA | 0 | 1 |
| Not Infected | NA | - | - | - | + | 1 | - | 0 | 1 |
| Not Infected | NA | - | - | - | - | - | NA | 1 | 0 |
| Not Infected | NA | - | - | - | NA | - | + | 1 | 0 |
Table 13. CT Infected Status for Performance Evaluation in Female Vaginal Swab, PreservCyt Solution Liquid Pap, and Endocervical Swab Specimens
AC2 = APTIMA COMBO 2, ACT = APTIMA CT Assoy, Asym = asymplomatic, CVS = clinician-collected vaginal swab, FS = female endocervical swab, FU = female urine, NA = result not available, I'ANTHER System, PCy = PreservCyt Solution liquid Pap. I'VS
= patient-collected vaginal swab, Sym = symptomatic, TIGRIS = TIGRIS DTS System
For the evaluation of the non-urine specimen types, the specimens were considered non-infected.
{23}------------------------------------------------
AC2 Assay on PANTHER
| Assay Results | Symptom Status | ||||||
|---|---|---|---|---|---|---|---|
| GC Infected Status | AC2 DTS | AGC DTS | AC2PANTHERMS | Sym | Asym | ||
| MS | MU | MS | MU | ||||
| Infected | + | + | + | + | + | 30 | 2 |
| Infected | + | + | + | + | NA | 0 | 1 |
| Infected | + | - | + | - | + | 1 | 1 |
| Infected | NA | + | NA | + | NA | 1 | 0 |
| Not Infected | - | - | NA | NA | - | 205 | 307 |
| Not Infected | - | - | NA | NA | NA | 14 | 9 |
Table 14. GC Infected Status for Performance Evaluation in Male Urethral Swab Specimens
AC2 = APTIMA COMBO 2, AGC = APTIMA GC Assay, Asym = asymplomatic, DTS = DTS Systems, MS = male urechral swab, MU = male urine, NA = result not available, PANTHER = PANTHER System, Sym = symptomatic, TIGRIS = TIGRIS DTS System
Table 15. GC Infected Status for Performance Evaluation in Female Vaginal Swab, PreservCyt Solution Liquid Pap, and Endocervical Swab Specimens
| AC2 TIGRIS | AGCTIGRIS | AC2PANTHER | Symptom Status | ||||||
|---|---|---|---|---|---|---|---|---|---|
| GC InfectedStatus | PCyt | FU | PCyt | FU | CVS/PVS | PCyt | FS | Sym | Asym |
| Infected | + | + | + | + | + | + | + | 22 | 10 |
| Infected | + | + | + | + | + | + | NA | 1 | 0 |
| Infected | + | + | + | - | + | + | + | 1 | 0 |
| Infected | + | + | + | = | + | + | + | 0 | 1 |
| Infected | + | - | + | - | + | + | + | 3 | 3 |
| Infected | + | - | + | - | + | + | + | 0 | 1 |
| Infected | + | NA | + | NA | + | + | + | 0 | 1 |
| Not Infected | + | NA | - | - | + | = | - | 0 | 1 |
| Not Infected | - | - | NA | NA | + | - | + | 0 | 1 |
| Not Infected | - | - | NA | NA | + | - | - | 3 | 0 |
| Not Infected | - | - | NA | NA | + | - | NA | 1 | 0 |
| Not Infected | - | - | NA | NA | - | - | + | 1 | 0 |
| Not Infected | - | - | NA | NA | - | - | - | 736 | 429 |
| Not Infected | - | - | NA | NA | - | - | = | 1 | 0 |
| Not Infected | - | - | NA | NA | - | - | NA | 32 | 9 |
| Not Infected | - | - | NA | NA | - | NA | - | 1 | 0 |
| Not Infected | - | - | NA | NA | NA | - | - | 18 | 6 |
| Not Infected | - | - | NA | NA | NA | - | NA | 10 | 3 |
AC2 = APTIMA COMBO 2, ACT = APTIMA CT Assay, Asym = asympiomatic, CVS = clinician-collected vaginal swab, FS = female cndocervical swab, FU = female urine, NA = result not available, PANTHER System, PCy = PreservCy Solution liquid Pap, PVS = patient-collected vaginal swab, Sym = symptomatic, TIGRIS = TIGRIS DTS System.
The equal symbol (=) represents an equivocal result on repeat testing.
{24}------------------------------------------------
RLU Distribution of APTIMA COMBO 2 Controls
The distribution of the RLU values for the APTIMA COMBO 2 controls is presented in Table 16 from all valid PANTHER System runs performed during the clinical performance study.
| Control | Statistic | Total RLU(×1000) |
|---|---|---|
| Positive Control, CT/Negative Control, GC | N | 66 |
| Maximum | 1335 | |
| Median | 1081.5 | |
| Minimum | 624 | |
| CV% | 11.2 | |
| Positive Control, GC/Negative Control, CT | N | 66 |
| Maximum | 1241 | |
| Median | 1172.0 | |
| Minimum | 1063 | |
| CV% | 3.2 |
Table 16. RLU Distribution of APTIMA COMBO 2 Controls
Reproducibility Study
APTIMA Combo 2 Assay reproducibility was evaluated at two external US laboratories and at Gen-Probe using the PANTHER System. Testing was performed using one lot of assay reagents and a total of six operators (two at each site). At each site, testing was performed over at least 10 days.
Reproducibility panel members were created using negative specimens processed with the APTIMA Specimen Collection Kit. The positive panel members were created by spiking with CT and/or GC organisms to result in panel members with expected targeted concentrations.
Table 17 shows the CT and GC concentrations for each panel member. Table 17 presents, for each panel member, RLU data in terms of mean, standard deviation (SD), and coefficient of variation (CV) between sites, between operators, between runs, within runs, and overall. Percent agreement with expected results is also shown. Samples with valid results were included in the analyses.
{25}------------------------------------------------
. AC2 Assay on PANTHER
Table 17. Reproducibility Data
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| TargetConcentration | BetweenSites | BetweenOperators | BetweenDays | BetweenRuns | WithinRuns | Total | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CT(IFU/mL) | GC(CFU/mL) | Agreed/N | Agrmt(%) | MeanRLU(x1000) | SD(x1000) | CV(%) | SD(x1000) | CV(%) | SD(x1000) | CV(%) | SD(x1000) | CV(%) | SD(x1000) | CV(%) | SD(x1000) | CV(%) |
| 0 | 0 | 178/180 | 98.9 | 6.2 | 1.2 | 19.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.2 | 131.7 | 8.3 | 133.0 |
| 0.25 | 0 | 180/180 | 100 | 1202.1 | 92.4 | 7.7 | 0.0 | 0.0 | 0.0 | 0.0 | 62.9 | 5.2 | 50.3 | 4.2 | 122.6 | 10.2 |
| 2.5 | 0 | 178/178 | 100 | 1184.5 | 90.9 | 7.7 | 0.0 | 0.0 | 0.0 | 0.0 | 53.8 | 4.5 | 34.6 | 2.9 | 111.1 | 9.4 |
| 25 | 0 | 180/180 | 100 | 1265.4 | 97.4 | 7.7 | 18.9 | 1.5 | 0.0 | 0.0 | 62.4 | 4.9 | 35.1 | 2.8 | 122.4 | 9.7 |
| 1000 | 0 | 180/180 | 100 | 1278.5 | 101.9 | 8.0 | 15.7 | 1.2 | 20.6 | 1.6 | 61.4 | 4.8 | 31.8 | 2.5 | 125.9 | 9.8 |
| 0 | 0.25 | 177/179 | 98.9 | 421.9 | 40.3 | 9.5 | 21.9 | 5.2 | 27.6 | 6.5 | 35.3 | 8.4 | 72.7 | 17.2 | 96.9 | 23.0 |
| 0 | 12.5 | 179/180 | 99.4 | 1141.8 | 11.9 | 1.0 | 0.0 | 0.0 | 44.4 | 3.9 | 37.3 | 3.3 | 75.8 | 6.6 | 96.2 | 8.4 |
| 0 | 125 | 180/180 | 100 | 1223.7 | 31.4 | 2.6 | 13.0 | 1.1 | 11.1 | 0.9 | 19.8 | 1.6 | 34.3 | 2.8 | 53.4 | 4.4 |
| 0 | 1250 | 180/180 | 100 | 1262.9 | 16.7 | 1.3 | 9.4 | 0.7 | 21.0 | 1.7 | 14.0 | 1.1 | 30.6 | 2.4 | 44.1 | 3.5 |
| 0 | 2500 | 180/180 | 100 | 1308.7 | 20.7 | 1.6 | 13.4 | 1.0 | 0.0 | 0.0 | 21.7 | 1.7 | 25.3 | 1.9 | 41.4 | 3.2 |
| 2.5 | 125 | 180/180 | 100 | 2467.6 | 71.9 | 2.9 | 31.5 | 1.3 | 21.7 | 0.9 | 64.8 | 2.6 | 44.4 | 1.8 | 113.1 | 4.6 |
| 2.5 | 2500 | 180/180 | 100 | 2453.3 | 76.2 | 3.1 | 30.9 | 1.3 | 0.0 | 0.0 | 62.5 | 2.5 | 51.6 | 2.1 | 115.4 | 4.7 |
| 1000 | 125 | 179/179 | 100 | 2503.8 | 74.0 | 3.0 | 38.5 | 1.5 | 0.0 | 0.0 | 59.1 | 2.4 | 39.1 | 1.6 | 109.4 | 4.4 |
| 1000 | 2500 | 180/180 | 100 | 2357.1 | 79.1 | 3.4 | 0.0 | 0.0 | 0.0 | 0.0 | 74.2 | 3.1 | 55.2 | 2.3 | 121.7 | 5.2 |
Agrm = agreement, CV = coefficient of variation, N = number of samples, RLU = relative light unit, SD = standard deviation.
: :
t
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None: Variability from some factors may be numerically negative, which can occur if the variability doe to those factors is very small. When this occuss, the variability as measured with standard deviation and %CV is set to 0. ·
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{26}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/26/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of what appears to be an abstract caduceus, a symbol often associated with healthcare.
Food and Drug Administration
10903 New Hampshire Avenue Silver Spring, MD 20993
MAY - 3 2012
0
Gen-Probe, Inc. Jody Fleming Regulatory Affairs Specialist 10210 Genetic Center Drive San Diego, CA 92121
Re: K111409
13 Trade/Device Name: APTIMA COMBO 2 Assay on the (PANTHER System) Regulation Number: 21 CFR 866.3120 Regulation Name: DNA Reagents, Neisseria Regulatory Class: II Product Code: LSL, MKZ, NSU Dated: April 20, 2012 Received: April 23, 2012
Dear Ms. Fleming:
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 class II (Special Controls), 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing pactice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter
{27}------------------------------------------------
Page 2 - Jody Fleming
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 advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Jary A. Harper
Sally A. Hoivat. Ph.D Director, Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{28}------------------------------------------------
Gen-Probe Incorporated
Indications for Use Form
510(k) Number (if known): K111409
Device Name: APTIMA COMBO 2® Assay
Indications For Use:
The PANTHER System is intended to fully automate amplified nucleic acid test (NAT) diagnostic assays currently developed by Gen-Probe Incorporated (San Diego, CA).
. .
{29}------------------------------------------------
Intended Use -- APTIMA COMBO 2 Assay
Intended Use
The APTIMA COMBO 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease using the PANTHER System as specified.
On the PANTHER System, the assay may be used to test the following specimens from symplomatic and asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt Solution, and patient-collected vaginal swab specimens.
'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)
AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Tauain Teldble
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K111409
Page 2 of 2
1.2 510K Indication For Use Form_Final Final with K Confidential Original 510(k) Submission
§ 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).