TIGRIS DTS GEN-PROBE APTIMA COMBO 2 ASSAY by GEN-PROBE, INC.

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 and/or Neisseria gonorrhoeae in clinician-collected endocervical, vaginal and male urethral swab specimens, patientcollected vaginal swab specimens', female and male urine specimens and gynecological specimens collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease using the TIGRIS DTS Automated Analyzer or semi-automated instrumentation as specified.

Device Description

AI/ML Overview

This document is an FDA 510(k) clearance letter for an in vitro diagnostic device, not an AI/ML medical device. Therefore, the requested information about acceptance criteria, study design, and performance metrics (especially those related to AI/ML such as multi-reader multi-case studies, human reader improvement with AI, or standalone algorithm performance) is not applicable or cannot be extracted from this document.

The document discusses the substantial equivalence of the TIGRIS® DTS® GEN-PROBE® APTIMA COMOBO 2® Assay to a legally marketed predicate device for the qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis and/or Neisseria gonorrhoeae.

Here's the information that can be extracted, noting the limitations related to your AI/ML specific questions:

1. Table of Acceptance Criteria and Reported Device Performance:

This document does not provide a table of quantitative acceptance criteria (e.g., sensitivity, specificity thresholds) or specific performance metrics (e.g., reported sensitivity, specificity values) from a clinical study. It is a clearance letter acknowledging substantial equivalence to a predicate device, not a detailed performance report. Such data would typically be found in the 510(k) submission itself, not the clearance letter.

2. Sample size used for the test set and the data provenance:

Test set sample size: Not specified in this document.
Data provenance: Not specified. Clinical studies supporting clearance typically involve multiple sites, which could be domestic or international, and data could be retrospective or prospective. This information is usually detailed in the submission, not the clearance letter.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This is irrelevant for an in vitro diagnostic assay like the APTIMA COMBO 2 Assay. The "ground truth" for such assays is typically established by reference laboratory methods (e.g., culture, NAATs) or clinical diagnosis, not by human expert interpretation of images or other data. Therefore, there's no concept of "experts establishing ground truth" in the way described for AI/ML imaging devices.

4. Adjudication method for the test set:

Not applicable for an in vitro diagnostic assay. Adjudication methods (like 2+1 or 3+1) are used to resolve disagreements among human readers, typically in image interpretation, which is not the function of this device.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

Not applicable. This is an in vitro diagnostic test for direct pathogen detection, not an AI-assisted diagnostic imaging or decision support system. Therefore, MRMC studies and the concept of human readers improving with AI assistance are irrelevant to this device.

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

The device itself is a standalone assay. It performs the detection of rRNA from Chlamydia trachomatis and/or Neisseria gonorrhoeae without human interpretation influencing the result of the assay itself. However, this is not an "algorithm only" in the sense of an AI model; it's a biochemical assay for pathogen identification. The results are typically interpreted by laboratory personnel. Performance studies for such devices evaluate the accuracy of the device's output against a reference standard.

7. The type of ground truth used:

While not explicitly stated in this clearance letter, for in vitro diagnostic assays detecting pathogens, the ground truth is typically established by:

Culture: For bacterial infections like N. gonorrhoeae.
Other highly sensitive and specific Nucleic Acid Amplification Tests (NAATs): Often used as a gold standard or "truth" for comparison, especially for C. trachomatis where culture is difficult.
Clinical diagnosis: Supported by other laboratory findings and patient symptoms.

8. The sample size for the training set:

Not applicable. This document refers to a molecular diagnostic assay, not an AI/ML model that requires a training set. The development of such assays involves analytical studies (assay optimization, limit of detection, cross-reactivity) and clinical studies (evaluating performance on patient samples), but there's no "training set" in the context of machine learning.

9. How the ground truth for the training set was established:

Not applicable, as there is no "training set" in the AI/ML sense for this device. Ground truth in the context of assay development is established through rigorous analytical and clinical validation against established reference methods.

Summary

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Brian J. Shea, RAC Regulatory Affairs Associate Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121-1589

AUG 1 7 2006

Re: K060652 Trade/Device Name: TIGRIS® DTS® GEN-PROBE® APTIMA COMOBO 2® Assay Regulation Number: 21 CFR 866.3390 Regulation Name: Neisseria spp. direct serological test reagents Regulatory Class: Class II Product Code: LSL, MKZ Dated: May 26, 2005 Received: May 30, 2005

Dear Mr. Shea:

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 Foond, Or to and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA), You may, therefore, market the device, subject to the general controls provisions of the Act The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements not the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Parts 20).

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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its tolli-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours.

Sally, atton

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

Device Name: TIGRIS® DTS® GEN-PROBE® APTIMA COMBO 2® Assay

Indications For Use:

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. 2 Gynecological specimens collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System have only been reviewed and cleared for use with the APTIMA Combo 2 Assay in the United States by the Food and Drug Administration (FDA).

Prescription Use	√
(Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K010652

Regulation Number and Section

§ 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).