The APTIMA Assay for Chlamydia trachomatis is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) in clinician-collected endocervical, vaginal and male urethral swab specimens, patient-collected vaginal swab specimens*, and female and male urine specimens. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of chlamydial urogenital disease.

*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.

Device Description

The APTIMA Assay for Chlamydia trachomatis is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of rRNA from Chlamydia trachomatis in clinician-collected endocervical, vaginal and male urethral swab specimens, patient-collected vaginal swab specimens, and female and male urine specimens. The APTIMA Assay for Chlamydia trachomatis (APTIMA CT Assay) may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of chlamydial urogenital disease.

AI/ML Overview

Acceptance Criteria and Device Performance for GEN-PROBE® APTIMA® Assay for Chlamydia trachomatis

Due to the nature of the provided document, which is a 510(k) summary for a diagnostic test, much of the detailed information regarding study design, sample sizes, and ground truth establishment (especially for training sets) is not explicitly present in the provided text. The document focuses on demonstrating substantial equivalence to predicate devices and detailing the intended use and performance characteristics.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria in a quantitative manner as typically seen for AI/ML validation. Instead, it compares the performance of the APTIMA CT Assay with cell culture, highlighting the superior sensitivity of NAATs. The focus is on demonstrating similar or improved performance compared to predicate devices or the "gold standard" of the time (cell culture).

The key performance characteristics highlighted are:

Acceptance Criteria (Implied)	Reported Device Performance (APTIMA CT Assay)
Higher clinical sensitivity than cell culture	Demonstrated higher clinical sensitivity than cell culture. (Buimer et al., 1996; Crothfelt et al., 1998; Jaschek et al., 1993; Stary et al., 1998) - Note: These are references to general NAAT performance, not specific APTIMA CT Assay data within this document.
Comparable performance to predicate NAATs	Implied through substantial equivalence to GEN-PROBE® APTIMA® Combo 2 Assay and Becton Dickenson ProbeTec™ ET System CT and CT/GC Assays.
Reduced issues of specimen inhibition compared to first-generation NAATs	Demonstrated benefits of target capture, TMA, and HPA in reducing specimen inhibition. (Chong et al., 2003; Gaydos et al, 2003)
In vitro qualitative detection of rRNA from Chlamydia trachomatis in various specimen types	Successfully detects rRNA from CT in clinician-collected endocervical, vaginal and male urethral swab specimens, patient-collected vaginal swab specimens, and female and male urine specimens.

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

The provided document does not explicitly state the specific sample sizes used for the test set. It references several external studies (e.g., Buimer et al., Crothfelt et al., Jaschek et al., Stary et al., Chong et al., Gaydos et al.) to support claims about NAAT performance and the benefits of the APTIMA CT Assay's technology. However, the exact sample sizes and the specific data used for the regulatory submission are not detailed within this text.

Data Provenance: The document does not specify the country of origin of the data referenced in the studies. The studies are described as comparing NAATs to cell culture or discussing technological advancements. The document indicates that "an estimated 783,242 new cases of C. trachomatis infections were reported in 2001 in the United States alone," suggesting a focus on the U.S. context, but this does not directly specify the origin of the clinical study data.

Retrospective or Prospective: The document does not explicitly state whether the studies referenced were retrospective or prospective.

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

The document does not provide details on the number or qualifications of experts used to establish ground truth for the test set. For C. trachomatis diagnostics, particularly in the context of comparisons to cell culture, the "ground truth" would typically be established by highly qualified clinical laboratory personnel adhering to established protocols for the reference method (e.g., cell culture).

4. Adjudication Method for the Test Set

The document does not explicitly state an adjudication method for the test set. Given that the "ground truth" for comparing diagnostic tests like this often relies on a reference method (like cell culture) rather than subjective expert interpretation, a complex adjudication process like 2+1 or 3+1 might not be applicable in the same way as it would for image-based diagnostic AI. Discrepancy resolution for discordant results between the new assay and the reference method would be the more relevant process, but this is not detailed.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are typically performed for devices that involve human readers interpreting output (e.g., medical images). The APTIMA CT Assay is an in vitro diagnostic test that provides a qualitative (positive/negative) result without human interpretation of complex patterns, thus an MRMC study is not relevant.

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

The APTIMA CT Assay is a standalone algorithm/device. It is an automated in vitro diagnostic test that provides a direct result from a clinical specimen without real-time human intervention in the interpretation of the core assay output. The performance described (e.g., sensitivity, specificity relative to cell culture) intrinsically represents its standalone performance.

7. The Type of Ground Truth Used

The primary type of ground truth used as a comparator for the performance assessment of NAATs (and by extension for the APTIMA CT Assay's claims) was cell culture. The document states: "Cell culture was once considered to be the 'gold standard' for detection of C. trachomatis." However, it then goes on to state that NAATs have demonstrated higher clinical sensitivity than culture, implying a shift in the perceived "gold standard" or at least a recognition of NAATs' superior performance.

8. The Sample Size for the Training Set

The document does not provide information regarding the sample size for a training set. This is typical for a traditional IVD. Unlike AI/ML devices that explicitly use "training data" to develop algorithms, traditional diagnostic assays are developed and optimized through laboratory research and verification studies, rather than machine learning on a predefined "training set."

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

Similarly to point 8, the concept of a "training set" with a defined "ground truth" in the AI/ML sense is not applicable to this traditional in vitro diagnostic device. The ground truth for developing and verifying such an assay would involve known positive and negative samples, characterized through established laboratory methods, including potentially thoroughly characterized clinical specimens or spiked samples with known concentrations of the pathogen. These would be used for assay optimization, specificity testing, and analytical sensitivity studies during development.

Summary

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SUMMARY OF SAFETY AND EFFECTIVENESS 2.0

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Ko43072-______________________________________________________________________________________________________________________________________________________________________________ The assigned 510(k) number is: __

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GEN-PROBE® APTIMA® Assay for Chlamydia trachomatis

General Information

Submitted By:	Gen-Probe Incorporated
	10210 Genetic Center Drive
	San Diego, California 92121
phone:	(858) 410-8000
fax:	(858) 410-8622

Company Contact:	Alan Maderazo, Ph.D., RAC
	Regulatory Affairs Specialist
phone:	(858) 410-8332
fax:	(858) 410-8622
e-mail:	alanma@gen-probe.com

Trade Name:	GEN-PROBE® APTIMA® Assay for Chlamydia trachomatis
Common or Usual Name:	rRNA target-amplified nucleic acid probe test for the in vitro diagnostic detection of Chlamydia trachomatis
Classification Name:	DNA Probe, Nucleic Acid Amplification, Chlamydia

Classification Code:	Class 1
Medical Specialty:	Microbiology
Product Code:	MKZ
Registration Number:	CFR 866.3120
Device Class:	1
Description:	Reagents used to identify chlamydia directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Chlamydia and provides epidemiological information on these diseases. Chlamydia are the causative agents of psittacosis (a form of pneumonia), lymphogranuloma venereum (a venereal disease), and trachoma (a chronic disease of the eye and eyelid).

Substantially Equivalent Devices:

GEN-PROBE® APTIMA® Combo 2 Assay

Becton Dickenson ProbeTec™ ET System CT and CT/GC Assays

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Device Description

Background on the Disease and Principle of the Test

The Disease

Chlamydia trachomatis (CT) infections are one of the most common sexually transmitted infections worldwide. In the United States alone, an estimated 783,242 new cases of C. trachomatis infections were reported in 2001(CDC, 2003). J

Chlamvdiae are nonmotile, gram-negative, obligate intracellular bacteria. The C. trachomatis species is comprised of fifteen serovars that can cause disease in humans. The serovars D through K are the major cause of genital chlamydial infections in men and women (Schachter, Children born to infected mothers are at significantly higher risk for inclusion 1985). conjunctivitis and chlamydial pneumonia (Beem and Saxon, 1977; Frommell et al., 1979; Schachter and Grossman, 1981).

Screening for the presence of these diseases is the cornerstone for prevention strategies. A large number of these cases may be asymptomatic or have symptoms that are not specific; this makes reduction of the prevalence of chlamydial and gonococcal infections difficult. An accurate and prompt diagnosis of these infections is important to ensure appropriate patient

Gen-Probe Incorporated

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management, to prevent disease complications and their associated medical costs, and to control transmission to uninfected partners.

Historical and Conventional Methods

Historically, several methods for C. trachomatis detection have been utilized in the clinical laboratory, including cell culture, direct fluorescent antibody testing, and enzyme immunoassay. More recent methodologies for C. trachomatis detection include direct DNA probe assays and nucleic acid amplification tests (NAATs). Cell culture was once considered to be the "gold standard" for detection of C. trachomatis. Culture is quite specific, but recent publications have demonstrated that NAATs have a higher clinical sensitivity than culture (Buimer et al., 1996; Crothfelt et al., 1998; Jaschek et al., 1993; Stary et al., 1998). Due to its lower clinical sensitivity and variable performance between laboratories, culture has been replaced in many laboratories by direct DNA probe and NAATs.

First generation NAATs for C. trachomatis have technological issues that have limited their performance. These issues include cumbersome specimen and specimen inhibition that can yield false negative results (Chernesky et al., 1996; Goessens et al, 1997; Mahony et al., 1998; Peterson et al., 1997; Toye et al, 1998; Vincelette et al., 1999). The GEN-PROBE APTIMA Assay for Chlamydia trachomatis (APTIMA CT Assay) is a second generation NAAT that utilizes target capture, Transcription-Mediated Amplification (TMA), and Hybridization Protection Assay (HPA) technologies to streamline specimen processing, amplify target rRNA, and detect amplicon, respectively. Recent studies comparing performance and specimen inhibition of various amplification systems have demonstrated the benefits of target capture, TMA, and HPA (Chong et al., 2003; Gaydos et al, 2003).

Patient Care and Public Health Implications

C. trachomatis infections are one of the most common sexually transmitted infections worldwide with an estimated 783,242 new cases of C. trachomatis infections were reported in

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2001 in the United States alone, (CDC, 2003). The C. trachomatis species is comprised of fifteen serovars that can cause disease in humans. The serovars D through K are the major cause of genital chlamydial infections in men and women (Schachter, 1985). C. trachomatis can cause nongonococcal urethritis, epididymitis, cervicitis, acute salpingitis, and Pelvic Inflammatory Disease (PID) (Cates and Wasserheit, 1991; Holmes et al., 1975; Schachter 1978; Schachter et al., 1975). C. trachomatis infections are often asymptomatic in both males and females. Children born to infected mothers are at significantly higher risk for inclusion conjunctivitis and chlamydial pneumonia (Beem and Saxon, 1977; Frommell et al., 1979; Schachter and Grossman, 1981).

Treatment of symptomatic patients is only partially effective because of the large percentage of asymptomatic patients.

Intended Use

*Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus symbol, which is often associated with healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the caduceus.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 2 7 2005

Alan Maderazo, Ph.D., RAC Regulatory Affairs Specialist Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121-4362

Re: K043072

Trade/Device Name: GEN-PROBE® APTIMA® Assay for Chlamydia trachomatic Regulation Number: 21 CFR 866.3120 Regulation Name: Chlamydia serological reagents Regulatory Class: Class I Product Code: MKZ Dated: November 5, 2004 Received: November 8, 2004

Dear Dr. Maderazo:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into 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 of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

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 (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Saqartys

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): K043072

Device Name: GEN-PROBE® APTIMA® Assay for Chlamydia trachomatis

Indications For Use:

*Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use.

Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign/Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of ____________________________________________________________________________________________________________________________________________________________________

510(k)_k043072

Gen-Probe Incorporated

Confidential

Regulation Number and Section

§ 866.3120 Chlamydia serological reagents.

(a)
Identification. Chlamydia serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to chlamydia in serum. Additionally, some of these reagents consist of chlamydia antisera conjugated with a fluorescent dye used to identify chlamydia directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusChlamydia and provides epidemiological information on these diseases. Chlamydia are the causative agents of psittacosis (a form of pneumonia), lymphogranuloma venereum (a venereal disease), and trachoma (a chronic disease of the eye and eyelid).(b)
Classification. Class I (general controls).