(90 days)
No
The device description focuses on biochemical and molecular techniques (target capture, TMA, DKA) for detecting and differentiating rRNA. There is no mention of AI or ML algorithms being used for data analysis, interpretation, or result determination beyond a simple cut-off based on RLU and kinetic curve type.
No.
The device is an in vitro diagnostic (IVD) test designed to detect and differentiate ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease. It is used for diagnosis, not for treating, mitigating, or preventing a disease or condition.
Yes
The Intended Use / Indications for Use section explicitly states that the device is "to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease."
No
The device description clearly outlines a complex in vitro diagnostic assay involving physical components like specimen transport tubes, magnetic microparticles, and chemical reagents, as well as a hardware system (PANTHER System) for processing and detection. While software is likely involved in the PANTHER System for data analysis and reporting, the core of the device is a physical assay and associated hardware.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use Statement: The very first sentence explicitly states "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...". The phrase "in vitro" is a key indicator of an IVD.
- Purpose: The assay is designed to detect specific nucleic acids (rRNA) from pathogens (CT and GC) in biological specimens (swabs, urine) collected from the human body. This is done outside of the body ("in vitro") to provide information for the diagnosis of disease.
- Specimen Types: The assay is used to test various human specimens (endocervical, vaginal, male urethral swabs, urine, PreservCyt Solution).
- Diagnostic Aid: The results of the assay are intended to "aid in the diagnosis" of chlamydial and/or gonococcal urogenital disease. This directly aligns with the purpose of IVDs, which are used to provide information for diagnostic purposes.
- Laboratory Use: The description mentions the assay being performed "in the laboratory" and on the "PANTHER System," which is a laboratory instrument.
All of these points clearly indicate that the APTIMA Combo 2 Assay is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The APTIMA Combo 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal 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, patient-collected vaginal swab specimens, and male urine 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.
Product codes
MKZ, LSL, NSU
Device Description
The APTIMA Combo 2 Assay combines the technologies of target capture, transcription-mediated amplification (TMA), and dual kinetic assay (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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
urogenital
Indicated Patient Age Range
Of the 580 male subjects, none 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.
Of the 1477 evaluable male subjects, 46 were 16 to 17 years of age, 155 were 18 to 20 years of age, 524 were 21 to 30 years of age, 279 were 31 to 40 years of age, and 473 were >40 years of age.
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Clinical Study 1:
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 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, 580 male urine, 1319 vaginal swab, 1330 PreservCyt Solution liquid Pap, 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 in-house). Samples with initial invalid, equivocal, or error results were retested. Eighteen (18) male urethral swab, 25 vaginal swab, 1 PreservCyt Solution liquid Pap. and 37 endocervical swab samples 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 Solution liquid Pap sample and 1 endocervical swab had final GC equivocal results and were excluded from the analyses.
Male urethral swab, male and female urine, and PreservCyt Solution liquid Pap 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 two reference NAATs (see Tables 10, 11, 13, and 14 for the infected status algorithms). For female subjects, if the positive NAAT results occurred only in the urine specimens and not in the PreservCyt Solution liquid Pap 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.
In addition, male urine samples tested with the APTIMA Combo 2 Assay on the PANTHER System were excluded from the performance analyses due to the low prevalence of GC in the study population, particularly in the asymptomatic subjects.
Clinical Study 2:
A prospective, multicenter clinical study was conducted to establish the performance characteristics of the APTIMA Combo 2 Assay on the PANTHER System in male urine specimens. Specimens were collected from symptomatic and asymptomatic men (n=1492) enrolled from 13 geographically and ethnically diverse US clinical research sites, and family planning, public health, men's 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 1492 subjects enrolled, 14 were withdrawn.
Two specimens were collected from each subject (1 urethral swab and 1 first-catch urine, in that order). The urethral swab specimens were clinician-collected, and urine specimens were collected by the subject at the clinic. Urine specimens from each subject were processed into multiple samples for CT/GC testing with different NAATs in accordance with the instructions in the appropriate specimen collection kit package insert. The male urine samples for APTIMA Combo 2 Assay testing on the PANTHER System were split among three external laboratories. All 1478 male urine samples from non-withdrawn subjects were tested with the APTIMA Combo 2 Assay on the PANTHER System in accordance with the APTIMA Combo 2 Assay package insert instructions. Samples with initial invalid, equivocal, or error results were retested. One male urine sample had a final invalid result and was excluded from the analyses. The invalid result was due to insufficient sample volume. Of the remaining 1477 evaluable male subjects, 46 were 16 to 17 years of age, 155 were 18 to 20 years of age, 524 were 21 to 30 years of age, 279 were 31 to 40 years of age, and 473 were >40 years of age.
Male urethral swab and urine samples were tested with cleared NAATs to establish the infected status (see Tables 13 and 15 for the infected status algorithms). The infected status algorithm used urethral swab and urine sample results from one reference CT and GC NAAT and urine sample results from two additional reference CT and GC NAATs to generate four reference results for each analyte. Subjects were categorized as infected if a positive result occurred in at least two of the reference NAATs. Subjects that could not be categorized as infected or not infected were excluded from the performance analyses: 1 subject had an indeterminate CT infected status and was excluded from the performance analyses for detection of CT.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical Sensitivity Study
Chlamydia trachomatis analytical sensitivity (limit of detection) was determined by testing 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, 5.0 IFU/mL urine). However, dilutions of less than 1 IFU/assay tested positive in the APTIMA Combo 2 Assay for the following 12 CT serovars: D, E, F, G, H, I, J, K, L1, L2, L2a and L3 (>=95% positivity was observed in samples containing CT concentrations of 1.89 IFU/mL).
Neisseria gonorrhoeae analytical sensitivity (limit of detection) was determined by testing dilutions of GC organisms in 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, 250 cells/mL urine). However, dilutions of less than 50 cell/assay tested positive in the APTIMA Combo 2 Assay for 30 different strains of GC (>=95% positivity was observed in samples containing GC concentrations of 0.36 CFU/mL).
Carryover Studies for the Panther System
Two studies were conducted to evaluate carryover on the PANTHER System.
- In the first study, carryover was assessed in multiple runs on three PANTHER Systems with 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 within the run. High titer samples were made using GC rRNA spiked into STM to give a final concentration equivalent to 2.5 x 10^5 CFU/mL. Five runs were performed on each of three PANTHER Systems. Carryover was calculated from a total of 2938 valid negative results. The overall carryover rate from this study was 0% with a 95% confidence interval of 0-0.1%.
- The second carryover study was conducted on one PANTHER System with high titer GC positive samples (GC rRNA spiked into STM at the equivalent of 2.5 x 10^0 CFU/mL) alternately processed with negative samples in a checkerboard format. Five checkerboard runs were performed. The overall carryover rate from this study was 0.74% (1/135 negative samples).
Freeze-Thaw Study
Gen-Probe conducted an in-house analytical study that compared the APTIMA Combo 2 Assay (PANTHER System) performance of fresh (non-frozen) versus frozen urines. These data support the use of prospectively-collected frozen specimens to establish the male urine specimen performance claims. Performance of sixty individual urine specimens was assessed after exposure to fresh (non-frozen) and frozen storage conditions.
There were no significant differences in sensitivity and specificity between fresh and frozen samples (upper and lower bound of the 95% CI for the difference in sensitivity and specificity was
§ 866.3390
Neisseria spp. direct serological test reagents.(a)
Identification. Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identifyNeisseria spp. from cultured isolates. Additionally, some of these reagents consist ofNeisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence ofNeisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusNeisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.(b)
Classification. Class II (performance standards).
0
510(k) SUMMARY
APTIMA Combo 2® Assay (on the PANTHER® System)
Attached is a 510(k) summary as described in 21 CFR 807.92
Sponsor Information
Submitted By:
| Name: | |
|---|---|
| Address: |
Hologic | Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121 (858) 410-8000
OCT 17 2013
Company Contact: Contact: Phone: Fax: Email:
Jody J. Fleming Regulatory Affairs Manager 858-410-8634 858-410-7876 jody.fleming@gen-probe.com
Date Prepared: July 18, 2012
General Information
| Trade Name: | APTIMA Combo 2® Assay |
|---|---|
| Common or Usual Name: | Ribosomal RNA (rRNA) target-amplified nucleic acid probe |
| test for the in vitro diagnostic detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae | |
| Classification Names: | DNA Probe, Nucleic Acid Amplification, Chlamydia |
| DNA Reagents, Neisseria |
1
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
Device:
APTIMA Combo 20 Assay (PANTHER® System); K111409 This premarket application is to clear the APTIMA Combo 2 Assay for use on the PANTHER System with the male urine specimen type.
Device Description
The APTIMA Combo 2 Assay combines the technologies of target capture, transcriptionmediated amplification (TMA), and dual kinetic assay (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 deox yadenosine 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
Page 2 of 35
2
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.
3
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 symptomatic and asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt Solution, patient-collected vaginal swab specimens, and male urine 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.
4
Comparison to Predicate
A comparison of the APTIMA Combo 2® Assay (PANTHER® System) with the addition of the male urine specimen type to the predicate APTIMA Combo 2® Assay (PANTHER® System) (K111409) is summarized below.
| Item | Predicate Device | Test Device
(with Male Urine Claim) |
|------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Number | K111409 | K132251 |
| Trade Name | APTIMA Combo 2®
Assay | APTIMA Combo 2® Assay |
| Instrument | PANTHER® System | PANTHER® System |
| Model Number | 303094 and 302923 | 303094 and 302923 |
| Device Class | II | II |
| Regulation Specialty | Microbiology | Microbiology |
| Qualitative /Quantitative
Assay | Qualitative | Qualitative |
| Function | Detection and differentiation of
rRNA from Chlamydia
trachomatis and Neisseria
gonorrhoeae | Same |
| Indications For Use /
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
symptomatic and asymptomatic
individuals: clinician-collected
endocervical, vaginal and male
urethral swab specimens. | 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. |
| Item | Predicate Device | Test Device
(with Male Urine Claim) |
| Indications For Use /
Intended Use
(Continued) | clinician-collected gynecological
specimens collected in the
PreservCyt Solution, patient-
collected vaginal swab
specimens.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. | clinician-collected gynecological
specimens collected in the
PreservCyt Solution, patient-
collected vaginal swab
specimens1, and male urine
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. |
| Specimen Types | Female specimens:
• Vaginal swab
• Endocervical swab
• ThinPrep.in PreservCyt
solution | Female specimens:
• Vaginal swab
• Endocervical swab
• ThinPrep in PreservCyt
solution |
| | Male Specimens:
• Urethral Swab | Male Specimens:
• Urethral Swab
• Urine |
| | Swabs:
After collection, transport and
store swab in transport tube at 2-
30°C and test within 60 days. If
longer storage is desired, freeze at
-20°C to -70°C for up to 365
days. | Swabs:
Same |
| Specimen
Transport/Storage | ThinPrep Liquid Pap in
PreservCyt:
Transport and store in PreservCyt
solution at 2-30°C for up to 30
days. After transfer to APTIMA
specimen transfer tube, store at
15-30°C for 14 days or store at
2-8°C for 30 days. If longer
storage is desired, freeze at -20°C
to -70°C for up to 365 days | ThinPrep Liquid Pap in
PreservCyt:
Same |
| Item | Predicate Device | Test Device
(with Male Urine Claim) |
| Specimen
Transport/Storage
(Continued) | | Urine:
After collection, transport the
processed urine specimens in the
APTIMA urine specimen
transport tube at $2°C$ to $30°C$ and
store at $2°C$ to $30°C$ until tested.
Processed urine specimens should
be assayed with the APTIMA
Combo 2 Assay within 30 days
of collection. If longer storage is
needed, freeze at $-20°C$ to $-70°C$
for up to 12 months after
collection. |
| Type of Assay | Nucleic Acid Amplification Test | Same |
| Technology* | Target Capture (TC),
Transcription-Mediated
Amplification (TMA),
Hybridization Protection Assay
(HPA) | Same |
| Detection Format | HPA which provides relative
light units (RLUs) that are
assessed against an established
assay cutoff | Same |
5
6
*A number of Gen-Probe APTIMA assays (that are based on TC, TMA, and HPA technologies) have
been cleared by FDA including: the APTIMA Combo 2 Assay (K060652), the APTIMA CT A (K061413) and the APTIMA GC Assay (K061509) for use on the automated TIGRIS System and the semiautomated DTS Systems.
7
Performance Data
Brief Description of Non-Clinical Data
The following analytical studies were conducted to support clearance of the male urine claim for the APTIMA Combo 2 Assay on the PANTHER System.
Analytical Sensitivity Study
Chlamydia trachomatis analytical sensitivity (limit of detection) was determined by testing 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, 5.0 IFU/mL urine). However, dilutions of less than 1 IFU/assay tested positive in the APTIMA Combo 2 Assay for the following 12 CT serovars: D, E, F, G, H, I, J, K, L1, L2, L2a and L3 (≥95% positivity was observed in samples containing CT concentrations of 1.89 IFU/mL).
Neisseria gonorrhoeae analytical sensitivity (limit of detection) was determined by testing dilutions of GC organisms in 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, 250 cells/mL urine). However, dilutions of less than 50 cell/assay tested positive in the APTIMA Combo 2 Assay for 30 different strains of GC (≥95% positivity was observed in samples containing GC concentrations of 0.36 CFU/mL).
8
Carryover Studies for the Panther System
Two studies were conducted to evaluate carryover on the PANTHER System. In the first study, carryover was assessed in multiple runs on three PANTHER Systems with 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 within the run. High titer samples were made using GC rRNA spiked into STM to give a final concentration equivalent to 2.5 x 105 CFU/mL. Five runs were performed on each of three PANTHER Systems. Carryover was calculated from a total of 2938 valid negative results. The overall carryover rate from this study was 0% with a 95% confidence interval of 0-0.1%.
The second carryover study was conducted on one PANTHER System with high titer GC positive samples (GC rRNA spiked into STM at the equivalent of 2.5 x 10° CFU/mL) alternately processed with negative samples in a checkerboard format. Five checkerboard runs were performed. The overall carryover rate from this study was 0.74% (1/135 negative samples).
Freeze-Thaw Study
Gen-Probe conducted an in-house analytical study that compared the APTIMA Combo 2 Assay (PANTHER System) performance of fresh (non-frozen) versus frozen urines. These data support the use of prospectively-collected frozen specimens to establish the male urine specimen performance claims. Performance of sixty individual urine specimens was assessed after exposure to fresh (non-frozen) and frozen storage conditions.
There were no significant differences in sensitivity and specificity between fresh and frozen samples (upper and lower bound of the 95% CI for the difference in sensitivity and specificity was 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, 580 male urine, 1319 vaginal swab, 1330 PreservCyt Solution liquid Pap, and 1310 endocervical swab samples) were tested with the APTIMA Combo 2 Assay on the PANTHER System in accordance with package insert
े This study included testing of male urine samples with the APTIMA Combo 2 Assay on the PANTHER System that were not included in the original performance results due to the low prevalence of GC in the study population. Page 14 of 35
14
instructions. The samples were split amongst three laboratories (two external laboratories and in-house). Samples with initial invalid, equivocal, or error results were retested. Eighteen (18) male urethral swab, 25 vaginal swab, 1 PreservCyt Solution liquid Pap. and 37 endocervical swab samples 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 Solution liquid Pap sample and 1 endocervical swab had final GC equivocal results and were excluded from the analyses.
Male urethral swab, male and female urine, and PreservCyt Solution liquid Pap 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 two reference NAATs (see Tables 10, 11, 13, and 14 for the infected status algorithms). For female subjects, if the positive NAAT results occurred only in the urine specimens and not in the PreservCyt Solution liquid Pap 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,
In addition, male urine samples tested with the APTIMA Combo 2 Assay on the PANTHER System were excluded from the performance analyses due to the low prevalence of GC in the study population, particularly in the asymptomatic subjects.
Clinical Study 2: Male Urine Specimen Clinical Study
A prospective, multicenter clinical study was conducted to establish the performance characteristics of the APTIMA Combo 2 Assay on the PANTHER System in male urine specimens. Specimens were collected from symptomatic and asymptomatic men (n=1492) enrolled from 13 geographically and ethnically diverse US clinical research sites, and family planning, public health, men's 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 1492 subjects enrolled, 14 were withdrawn.
Two specimens were collected from each subject (1 urethral swab and 1 first-catch urine, in that order). The urethral swab specimens were clinician-collected, and urine specimens were collected by the subject at the clinic. Urine specimens from each subject were processed into
Page 15 of 35
15
multiple samples for CT/GC testing with different NAATs in accordance with the instructions in the appropriate specimen collection kit package insert. The male urine samples for APTIMA Combo 2 Assay testing on the PANTHER System were split among three external laboratories. All 1478 male urine samples from non-withdrawn subjects were tested with the APTIMA Combo 2 Assay on the PANTHER System in accordance with the APTIMA Combo 2 Assay package insert instructions. Samples with initial invalid, equivocal, or error results were retested. One male urine sample had a final invalid result and was excluded from the analyses. The invalid result was due to insufficient sample volume. Of the remaining 1477 evaluable male subjects, 46 were 16 to 17 years of age, 155 were 18 to 20 years of age, 524 were 21 to 30 years of age, 279 were 31 to 40 years of age, and 473 were >40 years of age.
Male urethral swab and urine samples were tested with cleared NAATs to establish the infected status (see Tables 13 and 15 for the infected status algorithms). The infected status algorithm used urethral swab and urine sample results from one reference CT and GC NAAT and urine sample results from two additional reference CT and GC NAATs to generate four reference results for each analyte. Subjects were categorized as infected if a positive result occurred in at least two of the reference NAATs. Subjects that could not be categorized as infected or not infected were excluded from the performance analyses: 1 subject had an indeterminate CT infected status and was excluded from the performance analyses for detection of CT.
Chlamydia trachomatis Performance Results
Performance characteristics of the APTIMA Combo 2 Assay for CT detection were estimated for each specimen type and are displayed in Tables 4 and 5 combining data from the two clinical studies. Table 6 displays the clinical performance results by individual study. Performance was calculated by comparing PANTHER System results to an infected status algorithm, which differed between the two clinical studies (see Tables 10 through 12 for the CT infected status algorithms). Table 4 shows the sensitivity, specificity, positive 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.
16
| Specimen
Type¹ | n | TP | FP | TN | FN | Prev % | Sensitivity %
(95% CI)² | Specificity %
(95% CI)² | PPV %
(95% CI)³ | NPV %
(95% CI)³ |
|-------------------|------|-----|----|------|----|--------|----------------------------|----------------------------|--------------------|--------------------|
| 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) |
| 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) |
| MU | 1799 | 197 | 3 | 1589 | 10 | 11.5 | 95.2 (91.3-97.4) | 99.8 (99.4-99.9) | 98.5 (95.8-99.7) | 99.4 (98.9-99.7) |
1
'able 4: Performance Characteristics of the APTIMA Combo 2 Assay for CT Detection
Cl = onfidence increal, CVS = clinical swah, N = false positive, FF = false positive, FS = paintent = wh, NS = macurial swab, YV = nake collected valia, "N = neagaine, PV = n = true positive.
l at architect and, Precedes (1 ligol by, and crime sent see least and Clinical Sudy , symomte mate net semple realls are fon Clinical Study.
2 and architection and essels o
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.
17
Table 5 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.
Page 18 of 35
18
able 5: Performance Characteristics of the APTIMA Combo 2 Assay for CT Detection by Symptom Status
| Specimen-
Type¹ | Symptom
Status | n | TP | FP | TN | FN | Prev
% | Sensitivity %
(95% CI)² | Specificity %
(95% CI)² | PPV %
(95% CI)³ | NPV %
(95% CI)³ |
|--------------------|-------------------|------|-----|----|------|----|-----------|----------------------------|----------------------------|--------------------|--------------------|
| 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) |
| 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) |
| MU | Sym | 497 | 85 | 1 | 406 | 5 | 18.1 | 94.4 (87.6-97.6) | 99.8 (98.6-100) | 98.8 (94.1-100) | 98.8 (97.3-99.6) |
| | Asym | 1302 | 112 | 2 | 1183 | 5 | 9.0 | 95.7 (90.4-98.2) | 99.8 (99.4-100) | 98.2 (94.1-99.8) | 99.6 (99.1-99.9) |
Aya manais, C = caliciencia subjective, PP = dispositive, PP = disposities N.S = mierceda sol, M.S = mac cuecha sol, M.S = mac cuecha val. A.V. = mierceded value, M.S. = pres
Male urethral swab, vaginal swab, PreservCyt liquid Pap, and endocervical swab sample results are from Clinical Study 1, symptomatic male urine sample results are from Clinical Study 2, and
asymptomatic male urine sample results are from both studies.
Scored C!
Score Cl
PPV 95% Cl computed from the exact 95% Cl for the positive likelihood ratio, NPV 95% C1 computed from the regative likelihood ratio
Page 19 of 35
19
Table 6: Clinical Performance of the AC2 Assay on PANTHER for Detection of Chiamydia Trachomatis in Male Urine, by Study and
Symptom Status
| Study | Symptom
Status | | TP | FP | TN | FN | Prev
%) | Sensitivity % (95% CI)' | Specificity %
(95% Cl) | (95% Cl)2
PPV % | (95% CI)²
NPV % | |
|---------|-------------------|------|-----|----|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------|-----------------------|-------------------------|--|
| Study | Asymr | 323 | 40 | | 280 | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
2 | 13.0 | 95.2 (84.2 to 98. | 99.6 (98.0 to 99.5 | 97.6 (88.3 to 99.9) | 99.3 (97.6 to 99.9) | |
| | | | | | | | | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | | | | |
| Study 2 | Asymp | 979 | 72 | | Amazing American American American American American American American American American American American American American American American American American American Amer
903 | | 7.7
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | 96.0 (88.9 to 98.6) | 99.9 (99.4 to 100.L | 98.6 (93.0 to 100.0) | 99.9
99.7 (99.1 to 1 | |
| | Sympt | 497 | જરુ | | 406 | | 18. | 94.4 (87.6 to 97.6) | 99.8 (98.6 to 100.t | 98.8 (94.1 to 100.0) | 98.8 (97.3 to 99.6) | |
| | ้โจเจ | 1476 | 157 | | 309 | | 11.2 | 95.2 (90.7 to 97.5) | 99.8 (99.4 to 100. | 99.8
98.7 (95.7 to | 99.4 (98,8 to 99.7) | |
| | | | | | | | | | | | | |
Symptomatic
prevalence = incidence * Symptomatic
duration
Asympt = asymptomatic
Score Cl.
Score Cl.
PPV 95% Cl computed from the exact 95% Cl for Pestive Likelihood Ratio, NPV 95% Cl computed from the exact 95% Cl for Negative L
Page 20 of 35
20
Neisseria gonorrhoeae Performance Results
Performance characteristics of the APTIMA Combo 2 Assay for GC detection were estimated for each specimen type and are displayed in Tables 7 and 8 combining data from the two clinical studies. Table 9 displays the clinical performance results by individual study. The infected status algorithm differed between the two clinical studies (see Tables 13 through 15 for the GC infected status algorithms). Table 7 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.
21
| Specimen
Type¹ | n | TP | FP | TN | FN | Prev % | Sensitivity %
(95% CI)² | Specificity %
(95% CI)² | PPV %
(95% CI)³ | NPV %
(95% CI)³ |
|-------------------|------|----|----|------|----|--------|----------------------------|----------------------------|--------------------|--------------------|
| CVS/
PVS | 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) |
| MS | 546 | 34 | 0 | 512 | 0 | 6.2 | 100 (89.8-100) | 100 (99.3-100) | 100 (90.2-100) | 100 (99.3-100) |
| MU | 1797 | 75 | 5 | 1716 | 1 | 4.2 | 98.7 (92.9-99.8) | 99.7 (99.3-99.9) | 93.8 (86.7-97.8) | 99.9 (99.7-100) |
able 7: Performance Characteristics of the APTIMA Combo 2 Assay for GC Detectio
Cl = confieresal, CVS = clinicia-collected vab, FN = false nositive, FS = fende ndocemial swal, MC = male unter swal, MCF = mal unter = true positive
Vaginal swo. Preces Cy il quid Pop. colocer cicles web sample results are from Clinical Study I, sympondic natures and see from Clicicle Sudy 2, ad
espinsionale with collec
PPV 95% Cl 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.
22
Table 8 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.
23
Table 8: Performance Characteristics of the APTIMA Combo 2 Assay for GC Detection by Symptom Status
| Specimen Type | Symptom
Status | U | TP | FP | TN | FN | % សារ | Sensitivity % (95% CI)² | pecificity % (95% CI)² | PPV % 95% CI)3 | NPV% 95% CI)3 |
|----------------|----------------------------|------|-----|----|-------|----|-------|---------------------------|-----------------------------------------------------------------------------------------------------------------------|------------------|-----------------|
| CVS/ PVS | Sym | 802 | LT | ना | ﺎ ﻟﻠ | 0 | 3.4 | 00 (87.5-100 | 99.5 (98.7-99.8) | 87.1 (72.6-96.1) | 100 (99.6-100 |
| | Asym | 4 રહ | SI | l | 439 | l | ૩.5 | 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 | LT | | 802 | 0 | 3.3 | 00 (87.5-100) | 100 (99.5-100) | 100 (88.0-100) | 100 (99.6-100 |
| | Asym | 464 | ા ર | 0 | 448 | 0 | 3.4 | 00 (80.6-100) | 00 (99.1-100 | 100 (81.3-100) | 100 (99.3-100 |
| FS | Sym | 785 | 97 | | 758 | 0 | g g | 00 (87.1-100) | 99.9 (99.3-100) | 96.3 (82.4-99.9 | 00 (99.5-100 |
| | Asym | 453 | 91 | | 436 | 0 | 3.5 | 00 (80.6-100 | 99.8 (98.7-100 | 94.1 (74.3-99.8) | 100 (99.3-100) |
| MS | Sym · | 236 | । દ | 0 | 205 | 0 | 13.1 | 100 (89.0-100) | 00 (98.2-100 | 100 (89.5-100) | 00 (98.3-100 |
| | Asym | 310 | ದ | 0 | 307 | 0 | 1.0 | 00 (43.9-100) | 100 (98.8-100 | 100 (44.4-100 | 00 (99.3-100 |
| MU | Sym | 497 | 99 | | 430 | 0 | 13.3 | 100 (94.5-100 | 99.8 (98.7-100 | 98.5 (92.3-100 | 100 (99.2-100 |
| | Asym | 1300 | 6 | | 1 286 | | 0.8 | 90.0 (59.6-98.2 | 99.7 (99.2-99.9 | 69.2 (45.6-91.7) | 99.9 (99.7-100) |
| | m = asymptomatic, Cl = cor | | | | | | | | idence interval, CVS = clinician-collected vaginal swab, FN = false positive, FS = female endocervical swab, MS = mal | | |
All Propenia Creaming Cream Comments of Propential Proponies Proponio Productions Marchises Microsoft Marchiteria Marculares Microsoft Marculares (Marcular Processor Microsof
Vaginal swab, PreservCyt liquid Pap, endocervical swab, male urethral swab sample results are from Clinical Study 1, symptomatic male urine sample results are from Clinical Study 2, and
asymptomatic male urine sample results are from both studies.
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.
Page 24 of 35
24
Table 9. Clinical Performance of the AC2 Assay on PANTHER for Detection of Neisseria Gonorrhoeae in Male Urine, by Study an
Symptom Status
| Symptom
Status | n | TP | FP | TN | FN | Prev
(%) | Sensitivity %
(95% CI)¹ | Specificity %
(95% CI)¹ | PPV %
(95% CI)² | NPV %
(95% CI)² |
|-------------------|------|----|----|------|----|-------------|----------------------------|----------------------------|----------------------|----------------------|
| Asymp | 320 | 3 | 2 | 314 | 1 | 1.3 | 75.0 (30.1 to 95.4) | 99.4 (97.7 to 99.8) | 60 (22.4 to 93.0) | 99.7 (99.0 to 100.0) |
| Asymp | 980 | 6 | 2 | 972 | 0 | 0.6 | 100.0 (61.0 to 100.0) | 99.8 (99.3 to 99.9) | 75 (44.7 to 96.9) | 100 (99.7 to 100.0) |
| Sympt | 497 | 66 | 1 | 430 | 0 | 13.3 | 100.0 (94.5 to 100.0) | 99.8 (98.7 to 100.0) | 98.5 (92.3 to 100.0) | 100 (99.2 to 100.0) |
| Total | 1477 | 72 | 3 | 1402 | 0 | 4.9 | 100.0 (94.9 to 100.0) | 99.8 (99.4 to 99.9) | 96 (89.2 to 99.1) | 100 (99.7 to 100.0) |
sympt = asymptomatic, Prev = prevalence, Sympt = symptomat
Score Cl.
PPP 95% Cl computed from the exact 95% Cl for Positive Likelihood Ratio, NPV 95% Cl computed from the exact 95% Cl for Negative Likelihood Rati
Page 25 of 35
25
Chlamydia trachomatis Infected Status Tables
The frequency of test outcomes from reference NAAT and investigational PANTHER System testing is summarized in Tables 10 through 12 for CT.
| Assay Results | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| CT Infected | AC2 TIGRIS | ACT TIGRIS | AC2 PANTHER | Symptom Status | |||||
| Status | PCyt | FU | PCyt | FU | CVS/PVS | PCyt | ાજુ | Sym | Asym |
| Infected | + | + | + | + | + | + | + | ୧2 | 26 |
| Infected | + | + | + | + | + | + | - | 0 | - |
| Infected | + | + | + | + | + | + | NA | 3 | 0 |
| Infected | + | + | + | + | + | + | 0 | 2 | |
| Infected | + | + | + | + | - | + | + | 0 | - |
| Infected | + | + | + | + | NA | + | + | 1 | l |
| Infected | + | + | + | + | NA | + | NA | 2 | l |
| Infected | + | + | + | + | + | + | 4 | l | |
| Infected | + | - | + | + | NA | + | NA | 0 | 1 |
| Infected | + | + | " | t | + | + | 4 | 0 | |
| Infected | + | ( | + | - | t | + | 0 | - | |
| Infected | + | * | + | a | NA | + | + | 0 | ﻤﺴﺘ |
| Infected | + | NA | + | NA | + | + | + | 0 | 1 |
| Infected | + | NA | + | NA | - | + | 0 | l | |
| Infected | - | + | ・ | + | + | 1 | + | l | 0 |
| Infected | - | 十 | - | + | + | - | - | 2 | 0 |
| Infected | ﻌ | + | - | + | - | - | l | I | |
| Not Infected | + | - | ・ | • | 0 | 2 | |||
| Not Infected | - | + | - | - | - | l | 0 | ||
| Not Infected | ﺖ | - | + | - | + | - | + | 0 | l |
| Not Infected | - | - | + | - | - | 5 | 0 | ||
| Not Infected | - | - | - | + | + | - | 0 | - | |
| Not Infected | - | - | t | キ | + | - | NA | 0 | --- |
| Not Infected | - | + | - | " | 3 | ||||
| Not Infected | " | - | • | + | - | 中 | l | 0 | |
| Not Infected | - | + | " | - | + | 2 | 7 | ||
| Not Infected | - | - | + | NA | 2 | 0 | |||
| Not Infected | l | - | " | - | + | 2 | 2 | ||
| Not Infected | ト | - | - | 1 | - | - | 680 | 396 | |
| Not Infected | ( | " | - | NA | 29 | 8 | |||
| Not Infected | - | " | • | NA | ﺎ | 0 | |||
| Not Infected | - | • | NA | - | 17 | 4 | |||
| Not Infected | - | - | - | י | NA | י | NA | 8 | l |
| Not Infected | - | NV | - | - | - | - | - | 8 | 6 |
| Not Infected | - | NA | - | - | NA | 0 | l | ||
| Not Infected | NA | - | - | - | - | - | 0 | ﻤﺴﻌ | |
| Not Infected | NA | - | " | - | - | NA | ﺎ | 0 | |
| Not Infected | NA | - | " | NA | + | l | 0 |
Table 10: Clinical Study 1. CT Infected Status for Performance Evaluation in Female Vaginal Swab, PreservCyt Solution Liquid Pap, and Endocervical Swab Samples
AC2 = APTIMA Combo 2, ACT = APTIMA CT Assay, Asym = asymptomatic, CVS = clinician-collected vaginal swab, FS = female endocervical swab, FU = female urine, NA = result not available, PANTHER System, PC yt = PreservCyt Solution liquid Pap, PVS = patient-collected vaginal swab; Sym = symptomatic; TIGRIS = TIGRIS DTS System.
1 For the evaluation of the non-urine specimen types, the specimens were considered non-infected.
26
| CT Infected Status | Assay Results | AC2 DTS | ACT TIGRIS | AC2 PANTHER | Symptom 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 | - | - | - | NA | 10 | 9 | ||
| Not Infected | NA | - | - | - | NA | 1 | 2 |
Table 11: Clinical Study 1: CT Infected Status for Performance Evaluation in Male Urethral Swab Samples
.
AC2 = APTIMA Combo 2, ACT = APTIMA CT Assay, Asym = asymptomatic, MS = male ureibral swab, MU = male urine, NA = result not available, PANTHER System, Sym = symptomatic, TIGRIS = TIGRIS DTS System.
.
27
Table 12: Clinical Study 1 and Clinical Study 2. CT Infected Status for Performance Evaluation in Male Urine Samples
| Assay Results | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| CT Infected | ||||||||||
| Status | AC2¹ | ACT TIGRIS¹ | NAAT 1³ | NAAT 2¹ | AC2 | |||||
| PANTHER | Symptom | |||||||||
| Status | ||||||||||
| MS | MU | MS | MU | MU | MU | MU | Sym | Asy | ||
| Clinical Study I | ||||||||||
| Infected | + | + | + | + | + | 38 | ||||
| Infected | + | - | + | + | + | 2 | ||||
| Infected | + | + | + | - | - | 2 | ||||
| Clinical Study 2 | ||||||||||
| Infected | + | + | + | + | + | 73 | 66 | |||
| Infected | + | + | + | + | + | 2 | 1 | |||
| Infected | + | + | + | + | + | 0 | 1 | |||
| Infected | + | + | + | NA | + | 0 | 1 | |||
| Infected | + | + | - | + | + | 3 | 0 | |||
| Infected | + | + | - | + | - | 0 | 1 | |||
| Infected | + | + | + | + | + | 4 | 0 | |||
| Infected | + | + | + | + | - | 3 | 0 | |||
| Infected | + | = | + | - | 0 | 1 | ||||
| Infected | + | + | + | + | + | 5 | 4 | |||
| Clinical Study I | ||||||||||
| Not Infected | + | + | - | - | + | 1 | ||||
| Not Infected | + | - | - | - | - | 2 | ||||
| Not Infected | - | - | + | - | - | 2 | ||||
| Not Infected | - | - | + | + | 1 | |||||
| Not Infected | - | - | - | - | - | 273 | ||||
| Not Infected | NA | - | - | 2 | ||||||
| Clinical Study 2 | ||||||||||
| Not Infected | + | - | - | - | 1 | 6 | ||||
| Not Infected | - | + | - | + | + | 0 | 1 | |||
| Not Infected | - | - | + | - | + | 1 | 0 | |||
| Not Infected | - | - | + | - | - | 0 | 2 | |||
| Not Infected | - | - | - | = | - | 388 | 874 | |||
| Not Infected | - | - | - | - | - | 0 | 1 | |||
| Not Infected | - | - | - | NA | - | 10 | 18 | |||
| Not Infected | - | - | NA | - | - | 1 | 2 | |||
| Not Infected | - | NA | - | 2 | 0 | |||||
| Not Infected | NA | - | - | - | 4 | 0 |
AC2 = APTIMA Combo 2 Assay, ACT = APTIMA CT Assay, Asyn = asymptomatic, TIGRIS = 71GRIS DTS Systems, MS = male urethral swab samples, MU = male urine samples, NA = result not available, PANTHER System, Sym = symptomatic 'Male urethral swab and male urine samples were tested with the APTIMA Combo 2 Assay on the DTS Systems in Clinical Study 1 and on the TIGRIS System in Clinical Study 2.
3Male urethral swab and male urine samples were tested with the APTIMA CT Assay on the TIGRIS DTS Systems in Clinical Study 1. 3Male urine samples were tested with two FDA-cleared CT NAATs in Clinical Study 2.
Note: Data from asymptomatic men in Clinical Study 1 are combined with data from Clinical Study 2.
28
Neisseria gonorrhoeae Infected Status Tables
The frequency of test outcomes from reference NAAT and investigational PANTHER System testing is summarized in Tables 13 through 15 for GC.
| Assay Results | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| GC Infected | |||||||||
| Status | AC2 | ||||||||
| TIGRIS | AGC | ||||||||
| TIGRIS | AC2 | ||||||||
| PANTHER | Symptom Status | ||||||||
| 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 |
| Table 13: Clinical Study 1. GC Infected Status for Performance Evaluation in Female | |
|---|---|
| Vaginal Swab, PreservCyt Solution Liquid Pap, and Endocervical Swab |
AC2 = APTIMA Combo 2, AGC = APTIMA GC Assay, Asym = asymptomatic, CVS = clinician-collected vaginal swab, FS = female endocervical swab, FU = female urine, NA = result not available, PANTHER System, PCyt = PreservCyt Solution liquid Pap, PVS = patient-collected vaginal swab, Sym = symptomatic, TIGRIS = TIGRIS DTS System. The equal symbol (=) represents an equivocal result on repeat testing.
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Table 14: Clinical Study 1. GC Infected Status for Performance Evaluation in Male Urethral Swab Samples
| Assay Results | |||||||
|---|---|---|---|---|---|---|---|
| GC Infected | |||||||
| Status | AC2 DTS | AGC DTS | AC2 PANTHER | Symptom Status | |||
| MS | MU | MS | MU | MS | Sym | Asym | |
| 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 |
AC2 = APTIMA Combo 2, AGC = APTIMA GC Assay, Asym = asymptomatic, DTS = DTS Systems, MS = made urethral swab, MU = male urine, NA = result not available, PANTHER = PANTHER System, Sym = symptomatic,
Table 15. Clinical Study 1 and Clinical Study 2. GC Infected Status for Performance Evaluation in Male Urine Samples
| Assay Results | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| GC Infected | |||||||||
| Status | AC21 | AGC DTS2 | NAAT 11 | NAAT 23 | AC2 | ||||
| PANTHER | Symptom | ||||||||
| Status | |||||||||
| MS | MU | MS | MU | MU | MU | MU | Sym | Asym | |
| Clinical Study 1 | |||||||||
| Infected | + | + | + | + | + | 3 | |||
| Infected | + | - | + | - | - | 1 | |||
| Clinical Study 2 | |||||||||
| Infected | + | + | + | + | + | 63 | 4 | ||
| Infected | + | + | + | NA | + | 1 | 1 | ||
| Infected | - | + | + | - | + | 0 | 1 | ||
| Infected | NA | + | + | + | + | 2 | 0 | ||
| Clinical Study 1 | |||||||||
| Not Infected | - | - | NA | NA | + | 2 | |||
| Not Infected | - | - | NA | NA | - | 314 | |||
| Clinical Study 2 | |||||||||
| Not Infected | + | - | - | - | - | 2 | 4 | ||
| Not Infected | - | + | - | - | + | 0 | 1 | ||
| Not Infected | - | - | + | - | - | 6 | 2 | ||
| Not Infected | - | - | - | + | - | 1 | 0 | ||
| Not Infected | - | - | - | - | + | 1 | 1 | ||
| Not Infected | - | - | - | - | - | 407 | 945 | ||
| Not Infected | - | - | - | NA | - | 9 | 19 | ||
| Not Infected | - | - | NA | - | - | 1 | 2 | ||
| Not Infected | - | NA | - | - | - | 2 | 0 | ||
| Not Infected | NA | - | - | - | - | 2 | 0 |
AC2 = APTIMA Combo 2 Assay, AGC = APTIMA GC Assay, Asym = asymptomatic, DTS = DTS Systems, MS = male uretiral swab samples, MU = male urine samples, NA = result not available, PANTHER = PANTHER System, Sym = symptomatic 'Male urethral swab and male urine samples were tested with the APTIMA Combo 2 Assay on the DTS Systems in Clinical Study 1 and on the TIGRIS System in Clinical Study 2.
4Male urethral swab and male urine samples were tested with the APTIMA CT Assay on the DTS Systems in Clinical Study 1.
3Male urine samples were tested with two FDA-cleared GC NAATs in Clinical Study 2.
Note: Data from asymptomatic men in Clinical Study 1 are combined with data from Clinical Study 2.
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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 Clinical Study 1 and Clinical Study 2.
| Table 16: Clinical Study 1 and Clinical Study 2. RLU Distribution of APTIMA Combo 2 | |
|---|---|
| Controls |
| Total RLU (x1000) | |||
|---|---|---|---|
| Control | Statistic | Clinical Study 1 | Clinical Study 2 |
| N | 66 | 23 | |
| Maximum | 1335 | 1258 | |
| Positive Control, CT/ | |||
| Negative Control, GC | Median | 1081.5 | 1135.0 |
| Minimum | 624 | 910 | |
| CV% | 11.2 | 7.5 | |
| N | 66 | 23 | |
| Maximum | 1241 | 1311 | |
| Positive Control, GC/ | |||
| Negative Control, CT | Median | 1172.0 | 1174.0 |
| Minimum | 1063 | 1082 | |
| CV% | 3.2 | 4.9 |
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Reproducibility Studies
Reproducibility of the APTIMA Combo 2 Assay on the PANTHER System was evaluated in two different studies using panel members created with Specimen Transport Medium in Reproducibility Study 1 and using panel members created with clinical urine specimens in Reproducibility Study 2.
Reproducibility Study 1
APTIMA Combo 2 Assay reproducibility was evaluated with panel members created using Specimen Transport Medium at three external US laboratories using the PANTHER System. Testing was performed using one lot of assay reagents and a total of six operators (two at each site). Testing was performed over at least 10 days at each site. The negative panel member consisted of Specimen Transport Medium and positive panel members were created by spiking Specimen Transport Medium with lysate from 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 and the mean, standard deviation (SD), and coefficient of variation (CV) of the RLU data for each panel member between-sites, between-operators, between-days, between-runs, within-runs, and overall. Percent agreement with expected results is also shown. Only samples with valid results were included in the analyses.
32
| | Target
Concentration | | | | Between
Sites | | Between
Operators | | Between
Days | | Between
Runs | | Within
Runs | | Total | |
|----------------|-------------------------|------------------|-----|----------------|------------------|-----------|----------------------|-----------|-----------------|-----------|-----------------|-----------|----------------|-----------|---------------|-----------|
| CT
(IFU/mL) | GC
(CFU/mL) | Agmt
Agreed/N | (%) | RLU
(x1000) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) |
| 0 | 0 | 180/180 | 100 | 6 | 1.0 | 17.5 | 0.5 | 8.1 | 0.2 | 3.7 | 0.5 | 8.2 | 1.5 | 24.4 | 1.9 | 32.4 |
| 0.25 | 0 | 180/180 | 100 | 1207 | 45.0 | 3.7 | 17.3 | 1.4 | 0.0 | 0.0 | 35.1 | 2.9 | 66.9 | 5.5 | 89.7 | 7.4 |
| 2.5 | 0 | 180/180 | 100 | 1272 | 41.3 | 3.2 | 19.2 | 1.5 | 0.0 | 0.0 | 31.0 | 2.4 | 36.8 | 2.9 | 66.3 | 5.2 |
| 25 | 0 | 180/180 | 100 | 1292 | 43.7 | 3.4 | 14.9 | 1.2 | 7.7 | 0.6 | 35.1 | 2.7 | 36.3 | 2.8 | 68.8 | 5.3 |
| 1000 | 0 | 180/180 | 100 | 1294 | 48.1 | 3.7 | 14.3 | 1.1 | 26.8 | 2.1 | 29.6 | 2.3 | 34.8 | 2.7 | 73.0 | 5.6 |
| 0 | 0.25 | 180/180 | 100 | 589 | 92.2 | 15.7 | 19.9 | 3.4 | 28.1 | 4.8 | 21.2 | 3.6 | 44.8 | 7.6 | 110.2 | 18.7 |
| 0 | 12.5 | 179/179 | 100 | 1251 | 163.5 | 13.1 | 0.0 | 0.0 | 15.1 | 1.2 | 31.5 | 2.5 | 29.8 | 2.4 | 169.8 | 13.6 |
| 0 | 125 | 180/180 | 100 | 1295 | 168.3 | 13.0 | 6.7 | 0.5 | 33.4 | 2.6 | 21.1 | 1.6 | 33.3 | 2.6 | 176.2 | 13.6 |
| 0 | 1250 | 180/180 | 100 | 1309 | 166.5 | 12.7 | 0.0 | 0.0 | 28.4 | 2.2 | 27.6 | 2.1 | 31.2 | 2.4 | 173.9 | 13.3 |
| 0 | 2500 | 179/179 | 100 | 1305 | 170.9 | 13.1 | 11.4 | 0.9 | 30.4 | 2.3 | 15.2 | 1.2 | 32.2 | 2.5 | 177.5 | 13.6 |
| 2.5 | 125 | 178/178 | 100 | 2513 | 123.9 | 4.9 | 24.6 | 1.0 | 24.0 | 1.0 | 57.5 | 2.3 | 52.4 | 2.1 | 150.3 | 6.0 |
| 2.5 | 2500 | 180/180 | 100 | 2515 | 123.5 | 4.9 | 6.5 | 0.3 | 33.8 | 1.3 | 39.3 | 1.6 | 59.4 | 2.4 | 146.6 | 5.8 |
| 1000 | 125 | 179/179 | 100 | 2524 | 117.4 | 4.6 | 35.2 | 1.4 | 52.1 | 2.1 | 28.9 | 1.1 | 54.7 | 2.2 | 146.8 | 5.8 |
| 1000 | 2500 | 180/180 | 100 | 2525 | 118.2 | 4.7 | 21.6 | 0.9 | 38.7 | 1.5 | 54.8 | 2.2 | 48.5 | 1.9 | 145.9 | 5.8 |
Table 17: Reproducibility Study 1 Data
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Reproducibility Study 2
APTIMA Combo 2 Assay reproducibility was evaluated with panel members created using clinical urine specimens at two external US laboratories and in-house using the PANTHER System. Testing was performed using one lot of assay reagents and a total of six operators (two at each site). Testing was performed over at least 10 days at each site. The negative panel member consisted of negative urine and the positive panel members were created by spiking negative urine with lysate from CT and/or GC organisms to result in panel members with expected targeted concentrations. Table 18 shows the CT and GC concentrations for each panel member and the mean, SD, and CV of the RLU data for each panel member between-sites, between-operators, between-days, between-runs, within-runs, and overall. Percent agreement with expected results is also shown. Only samples with valid results were included in the analyses.
34
| Target
Concentration | | | | Between
Sites | | Between
Operators | | Between
Days | | Between
Runs | | Within
Runs | | Total | | |
|-------------------------|----------------|------------------|------|------------------|-----------|----------------------|-----------|-----------------|-----------|-----------------|-----------|----------------|-----------|---------------|-----------|------------------------|
| CT
(IFU/mL) | GC
(CFU/mL) | Agmt
Agreed/N | (%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | SD
(x1000) | CV
(%) | Mean
RLU
(x1000) |
| 0 | 0 | 178/180 | 98.9 | 1.2 | 19.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.2 | 131.7 | 8.3 | 133.0 | 6 |
| 0.25 | 0 | 180/180 | 100 | 92.4 | 7.7 | 0.0 | 0.0 | 0.0 | 0.0 | 62.9 | 5.2 | 50.3 | 4.2 | 122.6 | 10.2 | 1202 |
| 2.5 | 0 | 178/178 | 100 | 90.9 | 7.7 | 0.0 | 0.0 | 0.0 | 0.0 | 53.8 | 4.5 | 34.6 | 2.9 | 111.1 | 9.4 | 1185 |
| 25 | 0 | 180/180 | 100 | 97.4 | 7.7 | 18.9 | 1.5 | 0.0 | 0.0 | 62.4 | 4.9 | 35.1 | 2.8 | 122.4 | 9.7 | 1265 |
| 1000 | 0 | 180/180 | 100 | 101.9 | 8.0 | 15.7 | 1.2 | 20.6 | 1.6 | 61.4 | 4.8 | 31.8 | 2.5 | 125.9 | 9.8 | 1278 |
| 0 | 0.25 | 177/179 | 98.9 | 40.3 | 9.5 | 21.9 | 5.2 | 27.6 | 6.5 | 35.3 | 8.4 | 72.7 | 17.2 | 96.9 | 23.0 | 422 |
| 0 | 12.5 | 179/180 | 99.4 | 11.9 | 1.0 | 0.0 | 0.0 | 44.4 | 3.9 | 37.3 | 3.3 | 75.8 | 6.6 | 96.2 | 8.4 | 1142 |
| 0 | 125 | 180/180 | 100 | 31.4 | 2.6 | 13.0 | 1.1 | 11.1 | 0.9 | 19.8 | 1.6 | 34.3 | 2.8 | 53.4 | 4.4 | 1224 |
| 0 | 1250 | 180/180 | 100 | 16.7 | 1.3 | 9.4 | 0.7 | 21.0 | 1.7 | 14.0 | 1.1 | 30.6 | 2.4 | 44.1 | 3.5 | 1263 |
| 0 | 2500 | 180/180 | 100 | 20.7 | 1.6 | 13.4 | 1.0 | 0.0 | 0.0 | 21.7 | 1.7 | 25.3 | 1.9 | 41.4 | 3.2 | 1309 |
| 2.5 | 125 | 180/180 | 100 | 71.9 | 2.9 | 31.5 | 1.3 | 21.7 | 0.9 | 64.8 | 2.6 | 44.4 | 1.8 | 113.1 | 4.6 | 2468 |
| 2.5 | 2500 | 180/180 | 100 | 76.2 | 3.1 | 30.9 | 1.3 | 0.0 | 0.0 | 62.5 | 2.5 | 51.6 | 2.1 | 115.4 | 4.7 | 2453 |
| 1000 | 125 | 179/179 | 100 | 74.0 | 3.0 | 38.5 | 1.5 | 0.0 | 0.0 | 59.1 | 2.4 | 39.1 | 1.6 | 109.4 | 4.4 | 2504 |
| 1000 | 2500 | 180/180 | 100 | 79.1 | 3.4 | 0.0 | 0.0 | 0.0 | 0.0 | 74.2 | 3.1 | 55.2 | 2.3 | 121.7 | 5.2 | 2357 |
Table 18: Reproducibility Study 2 Data
·
ngmit = getentin, C.V = today-orming in, C = encuston, iF U = manstering int, S.D = dandarderiand.
Note: Variability from some lise which can occur if the variability du to
Page 35 of 35
・
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/35/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the bird-like figure. The logo is in black and white.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 17, 2013
Hologic/Gen-Probe Incorporated Jody J. Fleming, MBA, RAC Regulatory Affairs Manager 10210 Genetic Center Drive San Diego. CA, 92121
Re: K132251
Trade/Device Name: APTIMA Combo 20 Assay (on the PANTHER® System) Regulation Number: 21 CFR 866.3120 21 CFR 866.3390 Regulation Name: Chlamydia serological reagents Neisseria spp. direct serological test reagents Regulatory Class: II Product Code: MKZ, LSL, NSU Dated: July 22, 2013 Received: July 23, 2013
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. Isting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21. Parts 800 to 898. 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
36
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact 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/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 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/ReportalProblem/default.html 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/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Sally A. ዘመjyzat -S
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
37
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
...
1 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·
Form Approved: OMB No: 0910-0120 Expiration Date: December 31, 2013
Indications for Use
510(k) Number (if known):
Device Name: APTIMA Combo 20 Assay
Indications For Use:
The APTIMA Combo 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal 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, patient-collected vaginal swab specimens, and male urine 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 | AND/OR | Over-The-Counter Use |
|---|---|---|
| X | ||
| (Part 21 CFR 801 Subpart D) | (21 CFR 801 Subpart C) |
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)
Concurrence of Center for Devices and Radiological Health (CDRH)
Kathleen A. Simon S
2013.10.17 09:29:32 -04'00'
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