(46 days)
Not Found
No
The description focuses on standard molecular diagnostic techniques (target capture, TMA, DKA, chemiluminescent detection) and does not mention any AI or ML components. The "kinetic profiles" and "cut-off based on total RLU and kinetic curve type" are described as standard data analysis methods for this type of assay, not indicative of AI/ML.
No
Explanation: This device is an in vitro diagnostic (IVD) device used for qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in diagnosis. It does not provide therapy or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the Aptima Combo 2 Assay is used "to aid in the diagnosis of chlamydial and/or gonococcal disease."
No
The device description clearly outlines a complex in vitro diagnostic assay involving chemical reagents, magnetic microparticles, target capture, amplification, and chemiluminescent detection, all of which are hardware and chemical components, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The Intended Use statement explicitly states that the Aptima Combo 2 Assay is for "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 disease".
The term "in vitro" means "in glass" or "in the laboratory," referring to tests performed outside of the living body. The purpose of detecting and differentiating the rRNA from CT and GC is to "aid in the diagnosis" of specific diseases. These are key characteristics of 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 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, PreservCyt® Solution liquid Pap specimens, vaginal, throat, rectal, and male urethral swab specimens; patient-collected vaginal swab specimens1, and female and male urine specimens.
'Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The Aptima Multitest Swab Specimen Collection Kit has not been evaluated for home use.
The Aptima Combo 20 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 Tigris® DTS® Automated Analyzer or semi-automated instrumentation as specified. The assay may be used to test the following specimens from symptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; and female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; patient-collected vaginal swab specimens'; and female and male urine specimens. The assay is also intended for use with the testing of gynecological specimens, from both symptomatic and asymptomatic patients, collected in the PreservCyt® Solution.
IPatient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The Aptima Multitest Swab Specimen Collection Kit is not for home use.
Product codes (comma separated list FDA assigned to the subject device)
QEP, MKZ, LSL
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 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 nucleic acid chemiluminescent probes, which are complementary to a region of each target amplicon, are labeled with different acridinium ester molecules. The updated version of the Aptima Combo 2 assay incorporates a second CT probe, complementary to a unique region of the existing CT amplicon. This tandem probe provides detection coverage for the variant strains of C. trachomatis that emerged in 2019. The labeled probes combine with amplicon to form stable 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 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
endocervical, vaginal, throat, rectal, male urethral
Indicated Patient Age Range
Not Found
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Limit of Detection – Panther and Tigris: Analytical sensitivity for Finnish variant of Chlamydia trachomatis (FI-nvCT) was determined by testing dilutions of in vitro transcripts in negative urine specimens, negative ThinPrep specimens, and simulated swab matrix specimens. Thirty replicates of each dilution were tested on both the Panther system and Tigris system with each of three reagent lots of the updated AC2 assay for a total of 90 replicates per specimen type. The analytical sensitivity was determined to be less than one IFU per assay in urine, ThinPrep, and simulated swab matrix specimens.
Clinical Comparability: Clinical specimen agreement between the current version and updated version of the AC2 assay was evaluated using remnant swab specimens collected from patients undergoing CT and/or GC screening. A single replicate of each specimen was tested with both the current version and the updated version of the AC2 assay on the Panther System. The overall agreement was >99.0% for both CT and GC.
CT/GC Clinical Sample Agreement: The clinical panel agreement study evaluated the equivalence between the current and updated versions of the AC2 assay using 20 prepared CT/GC clinical panels containing 0 to 2,500 IFU/mL of wild type CT, 0 to 500 IFU/mL of FI-nvCT, and 0 to 125,000 CFU/mL of GC in urine specimens. Each of the 20 panels were tested in triplicate in two runs per day, on three Panther systems, by two operators, using three lots of reagents over seven days. The results show 100% (97.6-100%) total CT and GC agreement to the expected panel result for the updated AC2 assay. Results also show 100% (97.6-100%) total CT and GC agreement to the expected panel result for the current AC2 assay, with the exception of the moderate (0.2 IFU/mL) FI-nvCT only panel, which had 98.2% (93.5-99.5%) CT agreement and 99.1% (94.9-99.8%) GC agreement.
Microorganism Cross-Reactivity and Microbial Interference: The analytical specificity and microbial interference of the updated version of the AC2 assay was evaluated using 86 microorganisms consisting primarily of viral, bacterial, and yeast strains. Each pool of microorganisms was tested with and without the presence of FI-nvCT in vitro transcripts at a concentration of 3x LoD. None of the microorganisms tested were found to have an impact on the detection capabilities or analytical specificity of the updated version of the AC2 assay.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Specimen Comparison Results - CT:
Positive Percent Agreement (95% C.I.): 100% (92.7% - 100%)
Negative Percent Agreement (95% C.I.): 98.9% (96.9% - 99.6%)
Clinical Specimen Comparison Results - GC:
Positive Percent Agreement (95% C.I.): 100% (92.4% - 100%)
Negative Percent Agreement (95% C.I.): 99.6% (98.0% - 99.9%)
CT/GC Clinical Sample Agreement:
Updated AC2 assay: 100% (97.6-100%) total CT and GC agreement to the expected panel result.
Current AC2 assay: 100% (97.6-100%) total CT and GC agreement to the expected panel result (except FI-nvCT only panel); moderate (0.2 IFU/mL) FI-nvCT only panel: 98.2% (93.5-99.5%) CT agreement and 99.1% (94.9-99.8%) GC agreement.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s).
(a)
Identification. A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) is an in vitro diagnostic device intended for the detection and identification of nucleic acids from non-viral microorganism(s) and their associated resistance markers in clinical specimens collected from patients suspected of sexually transmitted infections. The device is intended to aid in the diagnosis of non-viral sexually transmitted infections in conjunction with other clinical and laboratory data. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist that are not detected by the device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;
(ii) Detailed discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate;
(iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) Limiting statements indicating that:
(A) A negative test result does not preclude the possibility of infection;
(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) Reliable results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(D) If appropriate (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type; and(v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that:
(A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present;
(B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora;
(C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and
(D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy.
(4) Design verification and validation must include:
(i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result (
e.g., how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies, including, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate.
(iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses.
(iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the symbol of the Department of Health & Human Services on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name written out next to it.
May 17, 2020
Hologic, Inc. Anila Tarte Regulatory Affairs Specialist 10210 Genetic Center Drive San Diego, California 92121
Re: K200866
Trade/Device Name: Aptima Combo 2 Assay (Panther System) and Aptima Combo 2 Assay (Tigris System) Regulation Number: 21 CFR 866.3393 Regulation Name: Nucleic Acid Detection System for Non-Viral Microorganism(s) Causing Sexually Transmitted Infections. Regulatory Class: Class II Product Code: QEP, LSL, MKZ Dated: March 30, 2020 Received: April 1, 2020
Dear Anila Tarte:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. 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.
1
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or post-marketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Steven Gitterman, M.D., Ph.D. Deputy Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
HOLOGIC®
510(k) SUMMARY
Aptima Combo 2® Assay (Panther® and Tigris® DTS® System)
I. SUBMITTER
Hologic, Inc. 10210 Genetic Center Drive San Diego, CA 92121
Contact Information:
| Anila Tarte | ||
|---|---|---|
| Regulatory Affairs Specialist | ||
| Phone: | 858-410-8055 | |
| Email: | anila.tarte@hologic.com |
Date Prepared: May 14, 2020
II. DEVICES
| Proprietary Name: | Aptima Combo 2® Assay (Panther® System) |
|---|---|
| Classification Name: | Nucleic Acid Detection System for Non-Viral Microorganism(s) |
| Causing Sexually Transmitted Infections | |
| Regulation Number: | 866.3393 |
| Regulatory Class: | Class II |
| Product Code: | QEP |
| Subsequent Product Code: | MKZ, LSL |
| Proprietary Name: | Aptima Combo 2® Assay (Tigris® DTS® System) |
| Classification Name: | Nucleic Acid Detection System for Non-Viral Microorganism(s) |
| Causing Sexually Transmitted Infections | |
| Regulation Number: | 866.3393 |
| Regulatory Class: | Class II |
| Product Code: | OEP |
3
III. PREDICATE DEVICE
The predicate device is the Aptima Combo 2 Assay on Panther and Tigris Systems (K200436; cleared 03/24/2020). The predicate device has not been subject to a design-related recall.
IV. DEVICE DESCRIPTIONS
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 nucleic acid chemiluminescent probes, which are complementary to a region of each target amplicon, are labeled with different acridinium ester molecules. The updated version of the Aptima Combo 2 assay incorporates a
4
second CT probe, complementary to a unique region of the existing CT amplicon. This tandem probe provides detection coverage for the variant strains of C. trachomatis that emerged in 2019. The labeled probes combine with amplicon to form stable 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 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.
V. DESCRIPTION OF DEVICE MODIFICATION
The clearance of this Special 510(k) application supports a change in formulation to the Probe reagent contained in the Aptima Combo 2 assay. Reformulation of the Probe reagent was necessary to detect recently emerged variants of Chlamydia trachomatis (CT) that were discovered outside of the U.S. using the Panther System or Tigris System. The updated version of the Aptima Combo 2 Assay (termed "updated AC2 assay") includes dual (redundant) CT detection probe, which not only identifies all recent variants of CT, but is also intended to provide diagnostic protection against future genetic variants within the AC2 probe region.
| Table 1: Aptima Combo 2 Assay - Catalog Numbers | |
|---|---|
| ------------------------------------------------- | -- |
| Kit Description | Current Kit
Cat. No. | Updated Kit
Cat. No. |
|-------------------------------------------------------|-------------------------|-------------------------|
| Aptima Combo 2 Assay, 100-Test Kit (Panther System) | 302923 | PRD-05576 |
| Aptima Combo 2 Assay, 250-Test Kit (Panther System) | 303094 | PRD-05571 |
| Aptima Combo 2 Assay, 250-Test Kit (Tigris System) | 301130 | PRD-05572 |
| Aptima Combo 2 Assay, 1000-Test Kit (Tigris System) * | 301130B | PRD-05572B |
- AC2 for Tigris 1000-Test Kit is packaged to contain four 250-Test Kits
5
VI. INDICATIONS FOR USE
Intended Use - Aptima Combo 2 Assay (Panther)
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 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, PreservCyt® Solution liquid Pap specimens, vaginal, throat, rectal, and male urethral swab specimens; patient-collected vaginal swab specimens1, and female and male urine specimens.
'Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The Aptima Multitest Swab Specimen Collection Kit has not been evaluated for home use.
Intended Use - Aptima Combo 2 Assay (Tigris)
The Aptima Combo 20 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 Tigris® DTS® Automated Analyzer or semi-automated instrumentation as specified. The assay may be used to test the following specimens from symptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; and female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; patient-collected vaginal swab specimens'; and female and male urine specimens. The assay is also intended for use with the testing of gynecological specimens, from both symptomatic and asymptomatic patients, collected in the PreservCyt® Solution.
IPatient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The Aptima Multitest Swab Specimen Collection Kit is not for home use.
6
VII. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICES
A comparison of the subject device to the predicate devices is summarized in Table 2 (AC2 assay on Panther) and Table 3 (AC2 assay on Tigris). Use of the updated AC2 assay does not change the principles of procedure, intended use, or primary technological characteristics. The similarities and differences between the subject and predicate devices are further discussed following the substantial equivalence tables. This discussion is the same for each assay.
Table 2: Comparison Between Predicate Device and Subject Device - AC2 Assay on the Panther System
| Item | Predicate Device
AC2 Assay (Panther)
K200436 | Subject Device AC2Assay (Panther)
K200866 |
|-----------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Technology
Principle of
Operation | Target Capture (TC), Transcription-Mediated
Amplification (TMA), Hybridization
Protection Assay (HPA) | Same |
| Platform | Automated Panther System | Same |
| Function | Detection and differentiation of rRNA from
Chlamydia trachomatis and Neisseria
gonorrhoeae | Same |
| Organisms
Detected | Chlamydia trachomatis (CT) and/or
Neisseria gonorrhoeae (GC) | Same |
| Patient
Population | Symptomatic and asymptomatic individuals | Same |
| 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,
throat, rectal, and male urethral swab
specimens clinician-collected gynecological | 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 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, PreservCyt® Solution
liquid pan specimens vaginal throat |
| Same* | | |
7
| Item | Predicate Device
AC2 Assay (Panther)
K200436 | Subject Device AC2Assay (Panther)
K200866 |
|------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | specimens collected in the PreservCyt®
Solution, patient-collected vaginal swab
specimens,1 and female and male urine
specimens. | rectal, and male urethral swab
specimens, patient-collected vaginal
swab specimens,1 and female and male
urine specimens. |
| | 1Patient-collected vaginal swab specimens are an
option for screening women when a pelvic exam
is not otherwise indicated. The Aptima Multitest
Swab Specimen Collection Kits have not been
evaluated for home use. | 1Patient-collected vaginal swab specimens
are an option for screening women when a
pelvic exam is not otherwise indicated. The
Aptima Multitest Swab Specimen Collection
Kit has not been evaluated for home use. |
- Edits to the intended use were made for clarification purposes only. Specimen types were aligned and/or grouped into respective clinician-collected and patient-collected specimen types
| Table 3: Comparison Between Predicate Device and Subject Device - AC2 Assay | |
|---|---|
| on the Tigris System |
| Item | Predicate Device
AC2 Assay (Tigris)
K200436 | Subject Device
AC2 Assay (Tigris)
K200866 |
|-----------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------|
| Technology
Principle of
Operation | Target Capture (TC), Transcription-Mediated
Amplification (TMA), Hybridization Protection Assay
(HPA) | Same |
| Platform | Automated Tigris System | Same |
| Function | Detection and differentiation of rRNA from Chlamydia
trachomatis and Neisseria gonorrhoeae | Same |
| Organisms
Detected | Chlamydia trachomatis (CT) and/or Neisseria
gonorrhoeae (GC) | Same |
| Patient
Population | Symptomatic and asymptomatic individuals | Same |
| 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
Tigris® DTS® Automated Analyzer. On the Tigris DTS
system, the assay may be used to test the following
specimens from symptomatic individuals: clinician-
collected endocervical, vaginal and male urethral swab
specimens; and female and male urine specimens. The
assay may be used to test the following specimens from
asymptomatic individuals: clinician-collected
endocervical, vaginal and male urethral swab specimens;
patient-collected vaginal swab specimens1; and female and | Same |
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| Item | Predicate Device
AC2 Assay (Tigris)
K200436 | Subject Device
AC2 Assay (Tigris)
K200866 |
|------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------|
| | male urine specimens. The assay is also intended for use
with the testing of gynecological specimens, from both
symptomatic and asymptomatic patients, collected in the
PreservCyt® Solution. | |
| | 1Patient-collected vaginal swab specimens are an option for screening
women when a pelvic exam is not otherwise indicated. The vaginal and
multitest swab specimen collection kits are not for home use. | |
Similarities
Both the predicate and subject devices utilize the same technology and principles of operation, mechanisms of action, and run on the same automated instrument systems. There are no changes to the assay kit configuration, intended use, results interpretation, or existing performance of the assay. Additionally, the proposed changes do not affect the existing Aptima Controls Kit, Aptima ancillary or collection kits, or the software and hardware associated with the use of the Panther or Tigris systems.
Differences
Changes to the user interface are minimal and include updated packaging and labeling to differentiate between the current AC2 assay kit and the updated AC2 assay kit. Package insert changes include new kit catalog numbers and updates to the Analytical Performance section demonstrating detection of all recent CT variants using the updated AC2 assay.
VIII. Design Control Activities
Hologic's overall product development activities are conducted per procedure, 'Product Development Procedure' which is in conformance with the design control requirements as specified in 21 CFR 820.30. Verification testing was performed to confirm clinical comparability between the current Probe and reformulated Probe reagents. The completed verification studies demonstrate that the reformulated Probe reagent does not impact assay performance, assay safety and effectiveness, and confirms that the modified assay meets the design input requirements.
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Hologic risk analysis activities are conducted per Product Safety Risk Management Procedure which is in conformance with ISO 14971:2007. Based on the results of the risk analysis and verification activities, and in accordance with ISO 14971:2007, all risks are reduced as far as possible and meet the pre-defined acceptability criteria. There were no hazards that fell within the "Undesirable" or "Unacceptable" residual risk regions. The device modifications do not introduce any new hazards or increase the overall residual risk as compared to the currently marketed products.
IX. ASSAY PERFORMANCE
Performance of the updated AC2 Assay was evaluated. The result of this evaluation demonstrated that existing performance and claims of the assay were not impacted due to the reformulated Probe reagent.
Brief Description of Non-Clinical Data
The following analytical (non-clinical) studies were conducted to support the clearance of the updated AC2 assay on the Panther System and Tigris System.
Limit of Detection – Panther and Tigris
The analytical sensitivity for the Finnish variant of Chlamydia trachomatis (FI-nvCT) was determined by testing dilutions of in vitro transcripts in negative urine specimens, negative ThinPrep specimens, and simulated swab matrix specimens. Thirty replicates of each dilution were tested on both the Panther system and Tigris system with each of three reagent lots of the updated AC2 assay for a total of 90 replicates per specimen type. The analytical sensitivity was determined to be less than one IFU per assay in urine, ThinPrep, and simulated swab matrix specimens. The detection capabilities of the updated version of the AC2 assay were confirmed across multiple CT variants.
Clinical Comparability
The clinical specimen agreement between the current version and updated version of the AC2 assay was evaluated using remnant swab specimens collected from patients undergoing CT
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and/or GC screening. A single replicate of each specimen was tested with both the current version and the updated version of the AC2 assay on the Panther System.
Table 4 and Table 5 show clinical comparison results for the CT and GC positive and negative percent agreement, respectively. The overall agreement was >99.0% for both CT and GC.
| Current AC2 Assay | |||
|---|---|---|---|
| CT Positive | CT Negative | ||
| Updated AC2 | |||
| Assay | CT Positive | 49 | 3 |
| CT Negative | 0 | 273 | |
| Positive Percent Agreement (95% C.I.): 100% (92.7% - 100%) | |||
| Negative Percent Agreement (95% C.I.): 98.9% (96.9% - 99.6%) |
Table 4: Clinical Specimen Comparison Results - CT
Table 5: Clinical Specimen Comparison Results - GC
| Current AC2 Assay | |||
|---|---|---|---|
| GC Positive | GC Negative | ||
| Updated AC2 | |||
| Assay | GC Positive | 47 | 1 |
| GC Negative | 0 | 275 | |
| Positive Percent Agreement (95% C.I.): 100% (92.4% - 100%) | |||
| Negative Percent Agreement (95% C.I.): 99.6% (98.0% - 99.9%) |
CT/GC Clinical Sample Agreement
The clinical panel agreement study evaluated the equivalence between the current and updated versions of the AC2 assay using 20 prepared CT/GC clinical panels containing 0 to 2,500 IFU/mL of wild type CT, 0 to 500 IFU/mL of FI-nvCT, and 0 to 125,000 CFU/mL of GC in urine specimens. Each of the 20 panels were tested in triplicate in two runs per day, on three Panther systems, by two operators, using three lots of reagents over seven days.
The results show 100% (97.6-100%) total CT and GC agreement to the expected panel result for the updated AC2 assay. Results also show 100% (97.6-100%) total CT and GC agreement to the expected panel result for the current AC2 assay, with the exception of the moderate (0.2 IFU/mL) FI-nvCT only panel, which had 98.2% (93.5-99.5%) CT agreement and 99.1% (94.9-99.8%) GC agreement. The percent agreement to the expected result for the detection of wild
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type CT and GC is comparable between the current AC2 assay and the updated AC2 assay. In addition, the observed variability of the current AC2 and the updated AC2 assays was comparable between instruments, lots, operators, days, and runs.
Microorganism Cross-Reactivity and Microbial Interference
The analytical specificity and microbial interference of the updated version of the AC2 assay was evaluated using 86 microorganisms consisting primarily of viral, bacterial, and yeast strains. Each pool of microorganisms was tested with and without the presence of FI-nvCT in vitro transcripts at a concentration of 3x LoD. None of the microorganisms tested were found to have an impact on the detection capabilities or analytical specificity of the updated version of the AC2 assay.
| Pool ID | Microorganism | Pool ID | Microorganism |
|---|---|---|---|
| 0 | SVSM (Control) | ||
| 1 | Acinetobacter lwoffii | ||
| Actinomyces israelii | |||
| Alcaligenes faecalis | |||
| Anaerococcus vaginalis | 12 | Proteus vulgaris | |
| Shigella dysenteriae | |||
| Shigella flexneri | |||
| Shigella sonneri | |||
| 2 | Arcanobacterium haemolyticum | ||
| Atopobium vaginae | |||
| Bacteroides fragilis | |||
| Bacteroides oralis | 13 | Stenotrophomonas maltophilia | |
| Streptococcus agalactiae | |||
| Streptococcus anginosus | |||
| Streptococcus pyogenes | |||
| 3 | Bifidobacterium adolescentis | ||
| Bordatella parapertussis | |||
| Campylobacter jejuni | |||
| Campylobacter rectus | 14 | Ureaplasma parvum | |
| Ureaplasma urealyticum | |||
| Veillonella parvula | |||
| Burkholderia cepacia | |||
| 4 | Citrobacter koseri | ||
| Corynebacterium diptheria | |||
| Corynebacterium genitalium | |||
| Corynebacterium pseudodiptheriticum | 15 | Clostridium difficile | |
| Prevotella bivia | |||
| Candida albicans | |||
| Cryptococcus neoformans | |||
| 5 | Eggerthella lenta | ||
| Enterobacter cloacae | |||
| Enterococcus faecalis | |||
| Escherichia coli | 16 | Entamoeba histolytica | |
| Giardia lamblia | |||
| Pentatrichomonas hominis | |||
| Trichomonas vaginalis |
Table 6: Cross-Reactivity Microorganisms
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| Pool ID | Microorganism | Pool ID | Microorganism |
|---|---|---|---|
| 6 | Fusobacterium necrophorum | ||
| Fusobacterium nucleatum | |||
| Gardnerella vaginalis | |||
| Helicobacter pylori | 17 | Adenovirus Type 07A | |
| Coronavirus 229E | |||
| Coxsackievirus B3 | |||
| Echovirus Type 11 | |||
| 7 | Haemophilus ducreyi | ||
| Haemophilus parahaemolyticus | |||
| Haemophilus parainfluenzae | |||
| Klebsiella pneumoniae | 18 | Enterovirus Type 68 | |
| Epstein-Barr virus | |||
| Hepatitis B Virus | |||
| Hepatitis C Virus | |||
| 8 | Lactobacillus acidophilus | ||
| Legionella (Tatlockia) micdadei | |||
| Legionella jordanis | |||
| Leptotrichia buccalis | 19 | HIV | |
| HPV 16 (SiHa cells) | |||
| HPV 18 (HeLa cells) | |||
| Human Metapneumovirus Type 20 | |||
| 9 | Listeria monocytogenes | ||
| Megasphaera Type 1 | |||
| Mobiluncus curtisii | |||
| Moraxella catarrhalis | 20 | HSV I | |
| HSV II | |||
| Influenza A H3N2 | |||
| Influenza B Massachusetts/2/12 | |||
| 10a | Mycoplasma genitalium | ||
| Mycoplasma hominis | |||
| Mycoplasma pneumoniae | 21 | Norovirus Group II | |
| Respiratory Syncytial virus Type B | |||
| Rhinovirus A16 | |||
| 10b | Neisseria gonorrhoeae | ||
| 11 | Peptostreptococcus micros | ||
| Propionibacterium acnes | |||
| Staphylococcus aureus | |||
| Staphylococcus epidermidis | 22 | Chlamydia pneumoniae | |
| Chlamydia psittaci | |||
| Chlamydia psittaci |
X. CONCLUSIONS
A comparison of the intended use, technological characteristics, and results from the analytical performance studies demonstrate that the updated AC2 assay on the Panther and Tigris systems performs comparably to the predicate device.