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, vaginal, throat, rectal, and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt® Solution, patient-collected vaginal swab specimens,1 and female and male urine 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 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 specimens1; 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.

The Aptima Trichomonas vaginalis Assay is an in vitro qualitative nucleic acid amplification test (NAAT) for the detection of ribosomal RNA (rRNA) from Trichomonas vaginalis to aid in the diagnosis of trichomoniasis using the Panther System. The assay may be used to test the following specimens from symptomatic or asymptomatic women: clinician-collected endocervical swabs. clinician-collected vaginal swabs, and specimens collected in PreservCyt Solution.

The Aptima Trichomonas vaginalis Assay is an in vitro qualitative nucleic acid amplification test (NAAT) for the detection of ribosomal RNA (rRNA) from Trichomonas vaginalis to aid in the diagnosis of trichomoniasis using the Tigris® DTS® System. The assay may be used to test the following specimens from symptomatic or asymptomatic women: clinician-collected endocervical swabs, clinician-collected vaginal swabs, female urine specimens, and specimens collected in PreservCyt Solution.

Device Description

The clearance of this Special 510(k) application will allow the use of a Ready-Made Reagent format for the Aptima Combo 2 assay (AC2) and the Aptima Trichomonas Vaginalis assay (ATV) on the Tigris and Panther systems. The use of Ready-Made Reagent assays does not change the principles of procedure, intended use, or primary technological characteristics.

Currently, each of the AC2 and ATV Amplification, Enzyme, and Probe reagents are provided in two parts: a lyophilized reagent (cake form) and a reconstitution solution (liquid form). Per the instructions provided in the respective assay's package inserts, the customers are instructed to prepare the reagents by reconstituting each reagent by combining the bottles of lyophilized reagent with the reconstitution solution and mixing reagents manually prior to placing on the Panther or Tigris system. Hologic developed "Ready Made Reagents" (RMRs), which are liquid format or pre-reconstituted Amplification, Enzyme, and Probe reagents available for customers to procure in the 250-Test Kit size available for use on both the Tigris and Panther systems.

Changes to the user interface are minimal as the RMRs are identical to the lyophilized reagents once they have been reconstituted at the laboratory. In order to prepare the current format reagents (lyophilized format), the laboratory personnel pairs each reconstitution solution (Amplification, Enzyme, and Probe) with its respective lyophilized reagent. Using the RMR format, the customer eliminates the reconstitution step and is only required to bring the three reagents to room temperature following the same process currently done for the previously reconstituted reagents. All subsequent steps by the operator are unchanged. All assay principles and processing steps on the Panther or Tigris systems remain unchanged. There are no changes to the instrument hardware or software based on this change.

AI/ML Overview

The provided text describes a 510(k) summary for new "Ready-Made Reagents" (RMRs) for the Aptima Combo 2 Assay and Aptima Trichomonas Vaginalis Assay, designed to simplify reagent preparation for laboratory personnel. The submission aims to demonstrate substantial equivalence to previously cleared predicate devices.

Here's an analysis of the acceptance criteria and study proving the device meets them, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a numerical table format with pre-defined thresholds. However, the implicit acceptance criteria for demonstrating substantial equivalence are based on comparability to the predicate devices, particularly in the analytical performance studies (Limit of Detection and Intended Use) and clinical performance studies. The goal is to show that the RMR format performs equivalently to the existing lyophilized format.

Implicit Acceptance Criteria (based on study design and conclusions):

Criterion Type	Specific Criterion (Implied)	Reported Device Performance (AC2 RMR vs. Current AC2 on Panther)	Reported Device Performance (AC2 RMR vs. Current AC2 on Tigris)	Reported Device Performance (ATV RMR vs. Current ATV on Panther)	Reported Device Performance (ATV RMR vs. Current ATV on Tigris)
Intended Use Study	100% agreement between RMR format and current format for negative, positive, and dual positive panels based on expected positivity.	100% agreement	100% agreement	100% agreement	100% agreement
Limit of Detection	LoD for RMR assay determined to be within ½ log of the LoD for the current assay, with ≥95% positivity at the lowest concentration equivalent to the current assay.	CT: 0.01 IFU/mL (equivalent to current) GC: 0.1 cells/mL (equivalent to current)	CT: 0.01 IFU/mL (equivalent to current) GC: 0.1 cells/mL (equivalent to current)	0.003 TV/mL (equivalent to current)	0.01 TV/mL (within ½ log of 0.003 TV/mL)
Clinical Performance	High positive, negative, and overall agreement between RMR format and current format when testing clinical specimens (for AC2 on Panther, used as general representative).	CT: Positive Agreement 100%, Negative Agreement 99.6%, Overall Agreement 99.7%GC: Positive Agreement 100%, Negative Agreement 99.6%, Overall Agreement 99.7%	Not explicitly stated but implied comparable based on AC2 Panther results generalizability	Not explicitly stated but implied comparable based on AC2 Panther results generalizability	Not explicitly stated but implied comparable based on AC2 Panther results generalizability

2. Sample Size Used for the Test Set and Data Provenance

Intended Use Study:
- The document mentions "negative and positive panels" and "CT positive, GC positive, and CT/GC dual positive panels" but does not specify the exact number of samples/panels used for each test.
- Data provenance is implicitly laboratory-generated (panels with known analytes), not clinical patient samples for this specific study section.
Limit of Detection Study:
- The document mentions using "stocks of CT and GC organisms in negative clinical liquid pap specimens" and "stocks of TV organisms in negative clinical liquid pap specimens".
- Does not specify a sample size (number of specimens/replicates) explicitly for the LoD determination.
- Data provenance appears to be laboratory-prepared samples using clinical specimen matrices.
Clinical Performance Study:
- Sample Size: Three hundred (300) remnant clinical swab specimens.
- Data Provenance: Retrospective, clinical samples ("remnant clinical swab specimens"). The country of origin is not specified but implicitly within the US as this is an FDA submission.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

Not applicable in the traditional sense of image-based AI studies using human expert consensus.
For these in vitro diagnostic (IVD) assays, the "ground truth" for the analytical and clinical studies is established through:
- Known concentrations in prepared panels (Intended Use, LoD).
- Reference assay results (the "current AC2 assay" or "current ATV assay" is used as the baseline/reference result in the clinical comparability study). This assumes the predicate device's performance is the established truth for comparison.

4. Adjudication Method for the Test Set

Not applicable in the context of human expert adjudication for a test set.
The "adjudication" is essentially the comparison of the RMR assay results against the predicate assay results or against known panel concentrations. Discrepancies would be investigated, but there's no mention of a multi-reader/adjudicator process.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study is more common for imaging AI devices where human readers interpret images with and without AI assistance.
This submission is for an in vitro diagnostic (IVD) assay where the device output is typically a qualitative (positive/negative) or quantitative result, not an interpretation by a human reader that is then augmented by AI. The comparison is directly between the new reagent format and the existing reagent format.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, in spirit, the studies are analogous to standalone performance. The performance evaluation of the RMR assays (the "device") is measured directly against established analytical and clinical benchmarks (predicate assay performance, known concentrations). There isn't a human-in-the-loop component for the performance evaluation of the assay itself, beyond the manual steps involved in sample preparation or loading described in the "Differences" section. The assay's output (presence/absence of target RNA) is the direct result.

7. The Type of Ground Truth Used

Analytical Truth: Known concentrations of target organisms in prepared panels (for Intended Use and Limit of Detection studies).
Comparative Truth: The previously cleared predicate devices (Aptima Combo 2 Assay and Aptima Trichomonas Vaginalis Assay using the lyophilized reagent format) served as the "reference result" or "baseline" for comparison in both analytical and clinical studies. This is a common approach in 510(k) submissions for modifications to existing devices.

8. The Sample Size for the Training Set

Not applicable. This submission is for a modification to an existing IVD assay (a change in reagent format), not for a machine learning or AI algorithm that requires a "training set." The assays are nucleic acid amplification tests (NAATs) based on established biochemical principles, not on learned patterns from a dataset.

9. How the Ground Truth for the Training Set was Established

Not applicable as there is no training set for this type of device.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services seal 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 to the right of it.

March 23, 2020

Hologic, Inc. Jill Wyland Director, Regulatory Affairs 10210 Genetic Center Drive San Diego, California 92121

Re: K200436

Trade/Device Name: Aptima Combo 2 Assay (Panther) - 250 test kit, Aptima Combo 2 Assay (Tigris) -250 test kit, Aptima Trichomonas Vaginalis (Panther) - 250 test kit, Aptima Trichomonas Vaginalis (Tigris) - 250 test kit Regulation Number: 21 CFR 866.3120 Regulation Name: Chlamydia Serological Reagents Regulatory Class: Class I, reserved Product Code: MKZ. LSL. OUY. OEP Dated: February 21, 2020 Received: February 24, 2020

Dear Jill Wyland:

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.

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

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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 postmarketing 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 medical devices and radiation-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

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HOLOGIC®

510(k) SUMMARY

Aptima Combo 2 Assay (Panther and Tigris System) Aptima Trichomonas Vaginalis Assay (Panther and Tigris System)

I. SUBMITTER

Hologic, Inc. 10210 Genetic Center Drive San Diego, CA 92121

Contact Information:

	Jill Wyland
	Director of Regulatory & Quality
Phone:	858-410-8487
Fax:	858-201-4188
Email:	jill.wyland@hologic.com

Date Prepared: February 21, 2020

II. DEVICES

Proprietary Name:	Aptima Combo 2® Assay (Panther System)
Classification Name:	Nucleic Acid Amplification System for Non-ViralMicroorganism(s) Sexually Transmitted InfectionsDNA Probe, Nucleic Acid Amplification, Chlamydia DNAReagents, Neisseria
Regulation Number:	866.3390
Regulatory Class:	Class II
Product Code:	QEP
Subsequent Product Code:	MKZ, LSL
Proprietary Name:	Aptima Combo 2® Assay (Tigris System)
Classification Name:	DNA Probe, Nucleic Acid Amplification, Chlamydia DNAReagents, Neisseria
Regulation Number:	866.3390
Regulatory Class:	Class II
Product Code:	MKZ, LSL

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Proprietary Name:Classification Name:Regulation Number:	Aptima Trichomonas Vaginalis® Assay (Panther System)Trichomonas Vaginalis Nucleic Acid Amplification Test System866.3860
Regulatory Class:	Class II
Product Code:	OUY
Proprietary Name:	Aptima Trichomonas Vaginalis Assay (Tigris System)
Classification Name:	Trichomonas Vaginalis Nucleic Acid Amplification Test System
Regulation Number:	866.3860
Regulatory Class:	Class II
Product Code:	OUY

III. PREDICATE DEVICES

The predicate devices are the following:

Aptima Combo 2 Assay (Panther System): K190515; cleared 05/23/2019) 0
o Aptima Combo 2 Assay (Tigris System): K060652: cleared 08/17/2006)
Aptima Trichomonas Vaginalis Assay (Panther System): K122062; cleared 01/09/2013) .
Aptima Trichomonas Vaginalis Assay (Tigris System): K102911; cleared 04/19/2011)

These predicate devices have not been subject to a design-related recall.

IV. DEVICE DESCRIPTIONS

Description of Ready-Made Reagents

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format or pre-reconstituted Amplification, Enzyme, and Probe reagents available for customers to procure in the 250-Test Kit size available for use on both the Tigris and Panther systems.

Assay Components

A list of the components that comprise the AC2 assay and the ATV assay master kits for both the RMR format and lyophilized format is provided in Table 5-01. Both kits are available for use on either the Panther or Tigris systems. There are no changes to the Aptima Controls Kit, ancillary kits, or collection kits.

Components for Lyophilized Kits	Components for RMR Format Kits
Box 1 (Stored at 2°C to 8°C)
Amplification Reagent	RMR Amplification Reagent
Enzyme Reagent	RMR Enzyme Reagent
Probe Reagent	RMR Probe Reagent
Target Capture Reagent B	Target Capture Reagent B
Box 2 (Stored at 15°C to 30°C)
Selection Reagent	Selection Reagent
Target Capture Reagent	Target Capture Reagent
Amplification Reconstitution Solution
Enzyme Reconstitution Solution
Probe Reconstitution Solution

Table 5-01: Reagents Required to Perform the AC2 and ATV Assays

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V. INDICATIONS FOR USE

There are not changes to the indications for use / intended use for each assay due to the use of the Ready-Made Reagents.

Intended Use - Aptima Combo 2 (Panther)

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 has not been evaluated for home use.

Intended Use - Aptima Combo 2 (Tigris)

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 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 specimens1; 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.

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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 is not for home use.

Intended Use - Aptima Trichomonas Vaginalis (Panther)

Intended Use - Aptima Trichomonas Vaginalis (Tigris)

The Aptima Trichomonas vaginalis Assay is an in vitro qualitative nucleic acid amplification test (NAAT) for the detection of ribosomal RNA (rRNA) from Trichomonas vaginalis to aid in the diagnosis of trichomoniasis using the Tigris® DTS® System. The assay may be used to test the following specimens from symptomatic or asymptomatic women: clinician-collected endocervical swabs, clinician-collected vaginal swabs, female urine specimens, and specimens collected in PreservCyt Solution.

VI. COMPARISON OF TECHNILOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICES

A comparison of the four subject devices (RMR assay format) to the predicate devices are summarized in Table 5-02 through Table 5-05. Use of the RMR assay format 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 last substantial equivalence table. This discussion is the same for each assay.

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Item	AC2 Assay (Panther)(Predicate Device)K190515	AC2Assay(Panther)(Subject Device)
TechnologyPrinciple ofOperation	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
OrganismsDetected	Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC)	Same
PatientPopulation	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 fromsymptomatic and asymptomatic individuals: clinician-collected endocervical, vaginal, throat, rectal, and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt® Solution, 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.	Same

Table 5-02: Comparison Between Predicate Device and Subject Device - AC2 on Panther

Table 5-03: Comparison Between Predicate Device and Subject Device - AC2 on Tigris

Item	AC2 Assay (Tigris)(Predicate Device)K060652	AC2 Assay (Tigris)(Subject Device)
TechnologyPrinciple ofOperation	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
OrganismsDetected	Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC)	Same

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Item	AC2 Assay (Tigris)(Predicate Device)K060652	AC2 Assay (Tigris)(Subject Device)
PatientPopulation	Symptomatic and asymptomatic individuals	Same
Intended Use	The Aptima Combo 2® Assay is a target amplification nucleicacid probe test that utilizes target capture for the in vitroqualitative detection and differentiation of ribosomal RNA(rRNA) from Chlamydia trachomatis (CT) and/or Neisseriagonorrhoeae (GC) to aid in the diagnosis of chlamydial and/orgonococcal urogenital disease using the Tigris® DTS®Automated Analyzer. On the Tigris DTS system, the assay maybe used to test the following specimens from symptomaticindividuals: clinician-collected endocervical, vaginal and maleurethral swab specimens; and female and male urine specimens.The assay may be used to test the following specimens fromasymptomatic individuals: clinician-collected endocervical,vaginal and male urethral swab specimens; patient-collectedvaginal swab specimens1; and female and male urine specimens.The assay is also intended for use with the testing ofgynecological specimens, from both symptomatic andasymptomatic patients, collected in the PreservCyt® Solution.1Patient-collected vaginal swab specimens are an option forscreening women when a pelvic exam is not otherwise indicated.The vaginal and multitest swab specimen collection kits are notfor home use.	Same

Table 5-04: Comparison Between Predicate Device and Subject Device - ATV on Panther

Item	ATV Assay (Panther)(Predicate Device)K122062	ATV Assay(Panther)(Subject Device)
TechnologyPrinciple ofOperation	Target Capture (TC), Transcription-Mediated Amplification(TMA), Hybridization Protection Assay (HPA)	Same
Platform	Automated Panther System	Same
Function	Detection and differentiation of rRNA from Trichomonasvaginalis	Same
OrganismsDetected	Trichomonas vaginalis	Same
PatientPopulation	Symptomatic and asymptomatic individuals	Same
Intended Use	The Aptima Trichomonas vaginalis Assay is an in vitroqualitative nucleic acid amplification test (NAAT) for thedetection of ribosomal RNA (rRNA) from Trichomonasvaginalis to aid in the diagnosis of trichomoniasis using the	Same

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Item	ATV Assay (Panther)(Predicate Device)K122062	ATV Assay (Panther)(Subject Device)
Panther System. The assay may be used to test the followingspecimens from symptomatic or asymptomatic women:clinician-collected endocervical swabs, clinician-collectedvaginal swabs, and specimens collected in PreservCyt Solution.

Table 5-05: Comparison Between Predicate Device and Subject Device – ATV on Tigris

Item	ATV Assay (Tigris)(Predicate Device)DEN110012; K102911	ATV Assay (Tigris)(Subject Device)
TechnologyPrinciple ofOperation	Target Capture (TC), Transcription-Mediated Amplification(TMA), Hybridization Protection Assay (HPA)	Same
Platform	Automated Tigris System	Same
Function	Detection and differentiation of rRNA from Trichomonasvaginalis	Same
OrganismsDetected	Trichomonas vaginalis	Same
PatientPopulation	Symptomatic and asymptomatic individuals	Same
Intended Use	The Aptima Trichomonas vaginalis Assay is an in vitroqualitative nucleic acid amplification test (NAAT) for thedetection of ribosomal RNA (rRNA) from Trichomonasvaginalis to aid in the diagnosis of trichomoniasis using theTigris® DTS® System. The assay may be used to test thefollowing specimens from symptomatic or asymptomaticwomen: clinician-collected endocervical swabs, clinician-collected vaginal swabs, female urine specimens, and specimenscollected in PreservCyt Solution.	Same

Similarities

Each of the subject devices utilize the same technology and principles of operation, mechanisms of action, conditions of use, results interpretation, have identical intended uses, and run on the same automated instrument system as compared to their predicate device. There are no differences in the performance of the assay as a result of the additional RMR format. The availability of the RMR format is a convenience for customers processing high volume of assays. The customer now has the option of procuring the AC2 and ATV assays using the RMR format in the 250-test kit size.

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Differences

For the four assays, changes to the user interface are minimal as the RMRs are identical to the lyophilized reagents once they have been reconstituted at the laboratory. In order to prepare the current format of assay reagents (lyophilized format), the laboratory personnel pairs each reconstitution solution (Amplification, Enzyme, and Probe) with its respective lyophilized reagent. Using the RMR format, the customer eliminates the reconstitution step and is only required to bring the three reagents to room temperature following the same process currently done for the previously reconstituted reagents. All subsequent steps by the operator are unchanged. All assay principles and processing on the Panther or Tigris System remain unchanged. Use of the RMR format required new kit packaging and updated package inserts to include the new kit configuration and product handling instructions.

VI. PERFORMANCE DATA

The following performance data are provided in support of the substantial equivalence determination.

Brief Description of Non-Clinical Data

The following analytical (non-clinical) studies were conducted to support the clearance of the AC2 RMR assay on the Panther system, AC2 RMR assay on Tigris, ATV RMR on Panther and ATV RMR on Tigris.

Intended Use Study

Aptima Combo 2 Assay (Panther)

A comparison of Intended Use results between the AC2 and AC2 RMR assays on the Panther system showed comparability when negative and positive panels were tested. AC2 panels consisting of a Negative panel, CT positive, GC positive, and CT/GC dual positive panels were run on two Panther instruments. The current AC2 assay was used as the baseline result. The results showed 100% agreement to the expected positivity results for each CT panel, GC Panel and with dual positive panel for both the current AC2 and AC2 RMR assays on Panther.

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Aptima Combo 2 Assay (Tigris)

A comparison of Intended Use results between the AC2 and pC2 RMR assays on the Tigris system showed comparability when negative and positive panels were tested. AC2 panels consisting of a Negative panel, CT positive, GC positive, and CT/GC dual positive panels were run on one Tigris instrument. The current AC2 assay was used as the baseline result. The results showed 100% agreement to the expected positivity results for each CT panel, GC Panel and with dual positive panel for both the current AC2 assay and AC2 RMR assay on the Tigris system.

Aptima Trichomonas vaginalis Assay (Panther)

A comparison of Intended Use results between the ATV and ATV RMR assays on the Panther system showed comparability when negative and positive panels were tested. ATV panels consisting of a Negative panel, TV positive, and TV low positive were run on two Panther instruments. The current ATV assay was used as the baseline results showed 100% agreement to the expected positivity results for each TV panel, for both the current ATV and ATV RMR assays on the Panther system.

Aptima Trichomonas vaginalis Assay (Tigris)

A comparison of Intended Use results between ATV and ATV RMR on the Tigris system showed comparability when negative and positive panels were tested. ATV panels consisting of a Negative panel, TV positive, and TV low positive were run on one Tigris instrument. The current ATV assay was used as the baseline results showed 100% agreement to the expected positivity results for each TV panel, for both the current ATV and ATV RMR assays on the Tigris system.

Limit of Detection

Aptima Combo 2 Assay (Panther)

The Limit of Detection (LoD) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) for AC2 RMR assay was determined to be within ½ log of the LoD for the AC2 assay on the Panther system. The limit of detection (LoD) was estimated for the current AC2 and AC2 RMR assays by using stocks of CT and GC organisms in negative clinical liquid pap specimens

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collected in PreservCyt solution (ThinPrep). These panels were tested on two Panther systems using two lots for each reagent format. The equivalency was shown as the results of the lowest concentration ≥ 95% positivity for CT target on the current AC2 assay and for AC2 RMR assay on the Panther was 0.01 IFU/mL. The equivalency for the GC target was equivalent as shown by the lowest concentration > 95% positivity for the current AC2 assay and for the AC2 RMR assay on the Panther was 0.1 cells/mL.

Aptima Combo 2 Assay (Tigris)

The Limit of Detection (LoD) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) for AC2 RMR assay was determined to be within ½ log of the AC2 assay on the Tigris system. The limit of detection (LoD) was estimated for the current AC2 and AC2 RMR assays by using stocks of CT and GC organisms in negative clinical liquid pap specimens collected in PreservCyt solution (ThinPrep). These panels were tested on one Tigris system using two reagent lots for each format. The equivalency was shown as the results of the lowest concentration > 95% positivity for CT target on the current AC2 assay and for AC2 RMR assay on Tigris was 0.01 IFU/mL. The equivalency for the GC target was equivalent as shown by the lowest concentration ≥ 95% positivity for the current AC2 assay and for the AC2 RMR assay on Tigris was 0.1 cells/mL.

Aptima Trichomonas vaginalis Assay (Panther)

The Limit of Detection (LoD) for Trichomonas vaginalis for ATV RMR assay was determined to be within ½ log of the LoD for the ATV assay on the Panther System. The limit of detection (LoD) was estimated for the current ATV and ATV RMR assays by using stocks of TV organisms in negative clinical liquid pap specimens collected in PreservCyt solution (ThinPrep). These panels were tested on two Panther Systems using two lots for each reagent format. The equivalency was shown as the results of the lowest concentration ≥ 95% positivity for TV target on the current ATV assay and for the ATV RMR assay on Panther was 0.003 TV/mL.

Aptima Trichomonas vaginalis Assay (Tigris)

The Limit of Detection (LoD) for Trichomonas vaginalis for ATV RMR assay was determined to be within ½ log of the LoD for the ATV assay on the Tigris System. The limit of detection

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(LoD) was estimated for the current ATV and ATV RMR assays by using stocks of TV organisms in negative clinical liquid pap specimens collected in PreservCyt solution (ThinPrep). These panels were tested on one Tigris System using two reagent lots for each format. The equivalency was shown as the results of the lowest concentration ≥ 95% positivity for TV target on the current ATV assay was 0.003TV/mL and for the ATV RMR assay on Tigris was 0.01 TV/mL.

Clinical Performance Study

Aptima Combo 2 Assay (Panther)

The clinical comparability was determined between the current AC2 assay and the AC2 RMR assay on the Panther system when evaluating clinical positive and negative specimens. Hologic demonstrated comparability using the AC2 assay on Panther as representative of both the ATV and AC2 assays for both the Tigris and Panther systems.

Three hundred (300) remnant clinical swab specimens were evaluated with the current AC2 assay and the AC2 RMR assay using two reagent lots of each assay format and across two Panther systems. The current AC2 assay was used as the reference result. The positive, negative and overall agreement between the AC2 and AC2 RMR assays were calculated for both CT and GC target interpretations.

	AC2
	+	-	Total
AC2RMR	+	47	1	48
	-	0	242	242
	Total	47	243	290

Table 5-06: CT Target Agreement Results

Positive agreement (95% CI) = 100% (92.4% - 100%) Negative agreement (95% CI) = 99.6% (97.7% - 99.9%) Overall agreement (95% CI) = 99.7% (98.1% - 99.9%)

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	AC2
	+	-	Total
AC2RMR	+	45	1	46
	-	0	245	245
	Total	45	246	291

Table 5-07: GC Target Agreement Results

Positive agreement (95% CI) = 100% (92.1% - 100%) Negative agreement (95% CI) = 99.6% (97.7% - 99.9%) Overall agreement (95% CI) = 99.7% (98.1% - 99.9%)

This study demonstrates that the performance of the current AC2 assay and AC2 RMR assay is comparable when testing clinical specimens on the Panther system.

VIII. CONCLUSIONS

A comparison of the intended use, technological characteristics, and results from the analytical performance studies demonstrate that the AC2 RMR assay and ATV RMR assay on the Panther and Tigris systems performs comparably to their predicate devices and supports a substantial equivalence decision.

Regulation Number and Section

§ 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.