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 ribonucleic acid (rRNA) from Chlamydia trachomatis and/or Neisseria gonorrhoeae in clinician-collected endocervical, vaginal, and male urethral swab specimens, patient-collected vaginal swab specimens* and male and female urine specimens. 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.

*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.

The APTIMA Vaginal Swab Specimen Collection Kit is for use with the APTIMA Assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The APTIMA Vaginal Swab Specimen Collection Kit is intended to be used for clinician and patient collection of vaginal swab specimens according to the instructions provided. Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The APTIMA Vaginal Swab Specimen Collection Kit is not for home use.

Device Description

Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Combo 2 Assay to include clinician-collected and patient-collected vaginal swabs (in a medical setting) as acceptable testing specimens. The ancillary kit formulated for this specific application is the GEN-PROBE APTIMA Vaginal Swab Specimen Collection Kit. The components of the APTIMA Vaginal Swab Specimen Collection Kit include: (1) a sterile swab for the collection of vaginal specimens and (2) a transport tube containing transport media with a penetrable cap.

The APTIMA Vaginal Swab Specimen Collection Kit is for use with the APTIMA Assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The APTIMA Vaginal Swab Specimen Collection Kit is intended to be used for clinician and patient collection of vaginal swab specimens according to the instructions provided. The APTIMA Vaginal Swab Specimen Collection Kit not for home use.

The APTIMA Combo 2 Assay incorporates the technologies of target capture, in vitro nucleic acid amplification, and hybridization of target amplicons with acridinium ester-labeled DNA probes to specifically detect and differentiate both C. trachomatis and N. gonorrhoeae nucleic acids in clinical specimens. GEN-PROBE's proprietary technologies are combined in this product to allow qualitative detection of C. trachomatis rRNA and N. gonorrhoeae rRNA.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the GEN-PROBE® APTIMA® Combo 2 Assay, based on the provided text:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied through the sensitivity and specificity values reported, which are compared against a "patient infected status algorithm" as the ground truth. While explicit numerical acceptance thresholds are not stated in the provided text (common in older 510(k) summaries which often relied on substantial equivalence to predicate devices), the study aims to demonstrate high performance.

Chlamydia trachomatis (CT)

Metric	Acceptance Criteria (Implied by High Performance)	Reported Performance (All Vaginal Swab Specimens)	Reported Performance (Patient-Collected Vaginal Swab)	Reported Performance (Clinician-Collected Vaginal Swab)
Sensitivity	High	96.6% (95% CI: 92.8 - 98.8%)	96.6% (95% CI: 92.8 - 98.8%)	96.7% (95% CI: 92.9 - 98.8%)
Specificity	High	97.8% (95% CI: 96.8 - 98.5%)	97.8% (95% CI: 96.8 - 98.5%)	97.1% (95% CI: 96.0 - 97.9%)

Neisseria gonorrhoeae (NG)

Metric	Acceptance Criteria (Implied by High Performance)	Reported Performance (All Vaginal Swab Specimens)	Reported Performance (Patient-Collected Vaginal Swab)	Reported Performance (Clinician-Collected Vaginal Swab)
Sensitivity	High	98.7% (95% CI: 93.0 - 100%)	98.7% (95% CI: 93.0 - 100%)	96.2% (95% CI: 89.2 - 99.2%)
Specificity	High	99.6% (95% CI: 99.0 - 99.8%)	99.6% (95% CI: 99.0 - 99.8%)	99.4% (95% CI: 98.8 - 99.7%)

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

The study was a multi-center clinical study involving 1,464 symptomatic and asymptomatic female subjects.

Sample Size:
- For CT analysis: 2,868 vaginal swab test results.
- For NG analysis: 2,867 vaginal swab test results.
- These numbers represent the combined results from patient-collected and clinician-collected vaginal swabs.
Data Provenance: The data was collected from subjects attending STD, OB/GYN, teen, and family planning clinics. The text does not explicitly state the country of origin, but given it's a US FDA submission, it's highly likely to be a prospective multi-center clinical study conducted in the United States.

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

The ground truth was established using an algorithm, not directly by human experts interpreting images or test results. Therefore, the concept of "number of experts" and "qualifications of those experts" as typically applied to expert review in imaging studies, does not directly apply here. The accuracy of the reference standard relies on the performance of the commercially available NAATs used.

4. Adjudication Method for the Test Set

The adjudication method for establishing the patient infected status was algorithmic (rule-based):

Subjects were considered infected with C. trachomatis or N. gonorrhoeae if two of the four reference NAAT results were positive (one specimen testing positive in each NAAT: APTIMA Combo 2 Assay and another commercially available NAAT, using endocervical swab and urine specimens).
Subjects were considered non-infected if less than two reference NAAT results were positive.

This method uses concordant results from multiple tests/specimens to define the "true" infection status.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This study is for an in vitro diagnostic (IVD) assay detecting biomarkers, not an AI-assisted diagnostic imaging device that involves human reader interpretation. Therefore, the concept of human readers improving with AI vs. without AI assistance does not apply.

6. Standalone Performance Study

Yes, a standalone performance study was done for the algorithm (the APTIMA Combo 2 Assay). The entire clinical study described evaluates the performance of the device on its own, comparing its results from vaginal swab specimens to the defined patient infected status algorithm. The reported sensitivity and specificity values are for the device operating as a standalone diagnostic tool for vaginal swab specimens.

7. Type of Ground Truth Used

The ground truth used was an algorithmic consensus based on multiple reference nucleic acid amplification tests (NAATs). Specifically:

Endocervical swab and urine specimen results from the commercially-available APTIMA Combo 2 Assay and another commercially-available NAAT were used.
Infection status was determined by requiring a positive result from both reference NAATs.
Culture was not used as a reference test for this specific study, as the APTIMA Combo 2 Assay had previously been evaluated against culture for other specimen types (as per K003395).

8. Sample Size for the Training Set

The document does not provide information regarding a distinct "training set" sample size. For an IVD assay like this, development typically involves analytical validation (sensitivity, specificity, interference etc.) and then clinical validation with a distinct set of clinical samples. The analytical studies (like analytical sensitivity, specificity, recovery, interference) might be considered analogous to early-stage development/testing, but a formal "training set" in the machine learning sense is not explicitly mentioned or typically applicable for this type of assay in this context. The clinical study described served as the primary performance evaluation.

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

As noted above, the concept of a separate "training set" with established ground truth in the machine learning context is not detailed. The primary clinical study used the algorithmic consensus described in point 4 as its ground truth for evaluating the device's performance.

Summary

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Summary of Safety and Effectiveness K032554

DEC 3 1 2003

2. SUMMARY OF SAFETY AND EFFECTIVENESS

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.

The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________

Gen-Probe Incorporated

Confidential

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GEN-PROBE® APTIMA® Combo 2 Assay GEN-PROBE® APTIMA® Vaginal Swab Specimen Collection Kit

Sponsor/Contact Information

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

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

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Summary of Safety and Effectiveness K032554

General Information

Trade Name:	GEN-PROBE® APTIMA® Combo 2 Assay
Common or Usual Name:	Ribosomal RNA (rRNA) target-amplified nucleic acid probetest for the in vitro diagnostic detection of Chlamydiatrachomatis and/or Neisseria gonorrhoeae
Classification Names:	DNA Probe, Nucleic Acid Amplification, ChlamydiaDNA Reagents, Neisseria

APTIMA Combo 2 Assay

Device Description	DNA Probe, Nucleic Acid Amplification, Chlamydi
Medical Specialty	Microbiology
Product Code	MKZ
Device Class	1
Regulation number	866.3120

Device Description	DNA Reagents, Neisseria
Medical Specialty	Microbiology
Product Code	LSL
Device Class	2
Regulation number	866.3390

Substantially Equivalent Devices:

APTIMA Combo 2 Assay; K003395

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Device Description

The APTIMA Vaginal Swab Specimen Collection Kit is for use with the APTIMA Assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The APTIMA Vaginal Swab Specimen Collection Kit is intended to be used for clinician and patient collection of vaginal swab specimens according to the instructions provided. The APTIMA Vaginal Swab Specimen Collection Kit not for home use.

The background information describing the relevant diseases, Chilamydia trachomatis and Neisseria gonorrhoeae, and the principles of the APTIMA Combo 2 Assay are provided in the Summary of Safety and Effectiveness for the APTIMA Combo 2 Assay (K003395)

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Intended Use

AC2 Assay package insert:

*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.

Ancillary Kit package insert:

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Summary of Technological Characteristics of the APTIMA Combo 2 Assay

Analytical Sensitivity

Chlamydia trachomatis analytical sensitivity (limits of detection) was determined by directly comparing dilutions of C. trachomatis organisms in cell culture and in the assay. The analytical sensitivity claim for the assay is one Inclusion-Forming Unit (IFU) per assay (7.25 IFU/swab, 5 IFU/mL urine) for all 15 C. trachomatis serovars. However, dilutions of less than one IFU/assay of all serovars tested positive in the APTIMA Combo 2 Assay.

Neisseria gonorrhoeae analytical sensitivity was determined by directly comparing dilutions of 57 different clinical isolates in culture and in the APTIMA Combo 2 Assay. The analytical sensitivity claim for the assay is 50 cells/assay (362 cells/swab, 250 cells/mL urine). However, all strains tested were positive at less than 50 cells/assay.

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Analytical Specificity

A total of 154 culture isolates were evaluated using the APTIMA Combo 2 Assay. These isolates included 86 organisms that may be isolated from the urogenital tract and 68 additional organisms that represent a phylogenetic cross-section of organisms. The tested organisms included bacteria, fungi, yeast, parasites, and viruses. All organisms except C. psittaci, C. pneumoniae, and the viruses were tested at 1.0x106 cells/assay in both swab and urine transport medium. C. psittaci and C. pneumoniae were tested at 1.0x10 TFU/assay. The viruses were tested as follows: (a) herpes simplex viruses I and II: 6.0x104 TCID50/assay, (b) human papilloma virus 16: 2.9x106 DNA copies/assay and (c) cytomegalovirus: 1x106 infected cell culture cells/assay. Only C. trachomatis and N. gonorrhoeae samples produced positive results in the APTIMA Combo 2 Assay. The list of organisms tested is shown in the following table.

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Analytical Specificity

ORGANISM	ORGANISM	ORGANISM
Achromobacter xerosis	Escherichia coli	Neisseria mucosa (3)
Acinetobacter calcoaceticus	Flavobacterium meningosepticum	Neisseria sicca (3)
Acinetobacter Iwoffi	Fusobacterium nucleatum	Neisseria subflava (14)
Actinomyces israelii	Gardnerella vaginalis	Neisseria perflava
Actinomyces pyogenes	Gemella haemolysans	Neisseria polysaccharea
Aerococcus viridans	Haemophilus ducreyi	Paracoccus denitrificans
Aeromonas hydrophila	Haemophilus influenzae	Peptostreptococcus anaerobius
Agrobacterium radiobacter	Herpes simplex virus I	Peptostreptococcus productus
Alcaligenes faecalis	Herpes simplex virus II	Plesiomonas shigelloides
Bacillus subtilis	Human papilloma virus 16	Propionibacterium acnes
Bacteriodes fragilis	Kingella dentrificans	Proteus mirabilis
Bacteriodes ureolyticus	Kingella kingae	Proteus vulgaris
Bifidobacterium adolescentis	Klebsiella oxytoca	Providencia stuartii
Bifidobacterium brevi	Klebsiella pneumoniae	Pseudomonas aeruginosa
Branhamella catarrhalis	Lactobacillus acidophilus	Pseudomonas fluorescens
Brevibacterium linens	Lactobacillus brevis	Pseudomonas putida
Campylobacter jejuni	Lactobacillus jensonii	Rahnella aquatilis
Candida albicans	Lactobacillus lactis	Rhodospirillum rubrum
Candida glabrata	Legionella pneumophila (2)	Saccharomyces cerevisiae
Candida parapsilosis	Leuconostoc paramensenteroides	Salmonella minnesota
Candida tropicalis	Listeria monocytogenes	Salmonella typhimurium
Chlamydia pneumoniae	Micrococcus luteus	Serratia marcescens
Chlamydia psittaci (2)	Moraxella lacunata	Staphylococcus saprophyticus
Chromobacterium violaceum	Moraxella osloensis	Staphylococcus aureus
Citrobacter freundii	Morganella morganii	Staphylococcus epidermidis
Clostridium perfringens	Mycobacterium smegmatis	Streptococcus agalactiae
Corynebacterium genitalium	Mycoplasma genitalium	Streptococcus bovis
Corynebacterium xerosis	Mycoplasma hominis	Streptococcus mitis
Cryptococcus neoformans	N. meningitidis Serogroup A	Streptococcus mutans
Cytomegalovirus	N. meningitidis Serogroup B	Streptococcus pneumoniae
Deinococcus radiodurans	N. meningitidis Serogroup C (4)	Streptococcus pyogenes
Derxia gummosa	N. meningitidis Serogroup D	Streptococcus salivarius
Eikenella corrodens	N. meningitidis Serogroup Y	Streptococcus sanguis
Enterobacter aerogenes	N. meningitidis Serogroup W135	Streptococcus griseinus
Enterobacter cloacae	Neisseria cinerea (4)	Trichomonas vaginalis
Enterococcus avium	Neisseria dentrificans	Ureaplasma urealyticum
Enterococcus faecalis	Neisseria elongata (3)	Vibrio parahaemolyticus
Enterococcus faecium	Neisseria flava	Yersinia enterocolitica
Erwinia herbicola	Neisseria flavescens (2)
Erysipelothrix rhusiopathiae	Neisseria lactamica (9)

(n) = number of strains tested

(1) - hamber or earline tested in the APTIMA Combo 2 Assay based on kinetic profile type and RLU.

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Interference Studies

The following table lists the commonly encountered substances found in vaginal swab specimens that were tested in the assay. All were tested for potential assay interference in the absence and presence of C. trachomatis and N. gonorrhoeae at the estimated rRNA equivalent of one C. trachomatis IFU/assay (5 fg/assay) and 50 N. gonorrhoeae cells/assay (250 fg/assay). The rRNA equivalents were calculated based on the genome size and estimated DNA:RNA ratio/cell of each organism.

Swab	Urine
10% Blood	30% Blood
Contraceptive jelly	Urine analytes:
Spermicide	Protein
Moisturizer	Glucose
Hemorrhoidal anesthetic	Ketones
Body oil	Bilirubin
Powder	Nitrate
Anti-fungal cream	Urobilinogen
Vaginal lubricants	pH 4 (acidic)
Feminine spray	pH 9 (alkaline)
Leukocytes (1 x 106 cells/mL)	Leukocytes (1 x 106 cells/mL)
	Cellular debris
	Vitamins
	Minerals
	Acetaminophen
	Aspirin
	Ibuprofen

Interfering Substances Testing

No interference was observed with any of the tested substances.

Gen-Probe Incorporated

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Recovery

Lactobacillus acidophilus, Gardnerella vaginalis, Bacteroides ureolyticus and Staphylococcus epidermidis (1 x 108 cells/assay) were added to pooled negative vaginal swab samples containing the rRNA equivalent of approximately one C. trachomatis IFU (5 fg) and 50 N. gonorrhoeae cells (250 fg). These additions did not interfere with the amplification and detection of C. trachomatis or N. gonorrhoeae rRNA using the APTIMA Combo 2 Assay.

Vaginal Swab Specimen Clinical Study Results

In the vaginal swab specimen multi-center clinical study, 1,464 symptomatic and asymptomatic female subjects attending STD, OB/GYN, teen, and family planning clinics were enrolled into the clinical study. Subjects were classified as symptomatic if symptoms such as discharge, dysuria, and pelvic pain were reported by the subjects were classified as asymptomatic if the subject did not report symptoms. Of the 646 asymptomatic subjects enrolled in the study, two were less than 16 years of age, 158 were between the ages of 16 and 20, 231 were between the ages of 21 and 25, and 255 were greater than 25 years of age. Of the 818 symptomatic subjects enrolled in the study, 160 were between the ages of 16 and 20, 324 were between the ages of 21 and 25, and 334 were greater than 25 years of age.

Five specimens were collected from each eligible subject; one urine specimen, one patientcollected vaginal swab, one clinician-collected vaginal swab, and two randomized endocervical swabs. APTIMA Combo 2 Assay results were generated from the two vaginal swabs, one of the endocervical swabs, and an aliguot of the urine specimen. The second endocervical swab and a second aliquot of the urine specimen were tested using another commercially-available nucleic acid amplification test (NAAT) for C. trachomatis and another commercially-available NAAT for N. gonorrhoeae. Endocervical swab and urine specimens tested in the APTIMA Combo 2 Assay and the other commercially available NAATs were used as reference NAATs to determine infected status for each subject in the vaginal swab specimen clinical study.

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Confidential

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Specimen testing was conducted either at the site of subject enrollment or at an external testing site.

All performance calculations were based on the total number of APTIMA Combo 2 Assay patient- and clinician-collected vaginal swab results compared to a patient infected status algorithm. A total of 2,868 C. trachomatis and 2,867 N. gonorrhoeae vaginal swab test results were used in the data analysis. In the algorithm, the designation of a subject as being infected or not infected with C. trachomatis or N. gonorrhoeae was based on endocervical swab and urine specimen results from the commercially-available APTIMA Combo 2 Assay and the other commercially-available NAAT. Subjects were considered infected with C. trachomatis or N. gonorrhoeae if two of the four endocervical swab and urine specimens tested positive in the APTIMA Combo 2 Assay and the other reference NAAT (one specimen testing positive in each NAAT). Subjects were considered non-infected if less than two reference NAAT results were positive. Tables 1 and 2 summarize the number of results from symptornatic and asymptomatic subjects designated as infected or non-infected with C. trachomatis or N. gonorrhoeae, respectively, according to the patient infected status algorithm. For this clinical study, two commercially available NAATs were used to determine GC-infected status. Culture was not used as a reference test since the APTIMA Combo 2 Assay has already been evaluated against culture for other specimen types (refer to K003395).

Sensitivity and specificity for C. trachomatis by gender, specimen type and symptom status are presented in Table 3. Table 4 shows the APTIMA Combo 2 Assay sensitivity, specificity, and predictive values for C. trachomatis compared to patient infected status for each clinical site and overall. Sensitivity and specificity for detection of N. gonorrhoeae by gender, specimen type and symptom status are presented in Table 5. Table 6 shows the N. gonorrhoeae sensitivity, specificity, and predictive values for the APTIMA Combo 2 Assay compared to patient infected status for each clinical site and overall. Samples that were APTIMA Combo 2 Assay positive and infected patient status negative (i.e., apparent false positives) were tested in alternate TMA assays for C. trachomatis and N. gonorrhoeae that targeted sequences unique

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from those targeted in APTIMA Combo 2. The results of the alternate TMA assays were not used to change the original patient categorizations (Tables 3 and 5).

Of the 1,464 subjects enrolled, there were 13 subjects with unknown CT patient infected status and 14 subjects with unknown GC patient infected status. Subjects were designated with an unknown patient infected status if results were missing that prevented conclusive determination of infected status. These subjects' results were not included in any performance calculations. Of the 5,782 APTIMA Combo 2 Assay vaginal swab results from the multi-center clinical study, there was a small percentage (28, 0.5%) of vaginal swab specimens that initially tested invalid or equivocal for CT or GC. Upon repeat testing only three C. trachomatis results and two N. gonorrhoeae results were equivocal and were excluded from the analysis. No specimens tested invalid on repeat testing.

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EffectivenessandSafetyof
.mary	K032554
r

NAAT 1		NAAT 2 (APTIMA Combo 2 Assay)		APTIMA Combo 2 Assay		Symptom Status		Total
Patient Infected Status	Endocervical Swab	Urine	Endocervical Swab	Urine	Patient-Collected Vaginal Swab	Clinician-Collected Vaginal Swab	Symptomatic	Asymptomatic
Infected	+	+	+	+	+	+	79	43	122
Infected	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	N/A	+	8	5	13
Infected	+	+	+	-	N/A	+	1	0	1
Infected	+	+	+	=	+	+	1	0	1
Infected	+	+	+	+	+	+	8	3	11
Infected	+	+	+	+	+	+	1	2	3
Infected	+	+	+	N/A	+	+	1	0	1
Infected	+	+	+	+	+	+	5	3	8
Infected	+	+	+	+	+	+	5	0	5
Infected	+	+	+	+	+	+	2	0	2
Infected	+	+	+	+	+	+	1	4	5
Non-infected	-	-	-	-	-	-	0	1	1
Non-infected	-	-	-	-	-	-	0	4	4
Non-infected	-	-	-	-	-	-	2	1	3
Non-infected	-	-	-	-	N/A	-	6	4	10
Non-infected	-	+	-	+	-	+	1	0	1
Non-infected	-	+	-	+	-	+	4	2	6
Non-infected	-	+	-	+	-	+	1	0	1
Non-infected	-	+	-	+	-	+	2	0	2
Non-infected	-	+	-	+	-	+	1	2	3
Non-infected	-	+	-	+	-	+	2	3	5
	NAAT		T 2 (APTIMA Combo Assay)NA			PTIMA Combo 2 Assa		/mptom Stat
tient Infecte Status	ndocervicSwab	Urine	EndocervicaSwab	Urine	Patient- Collected Iginal Swa	Clinician- Collected Taginal Swa	mptomatic	Asymptomat	Госа
					-+-
	l					+	ਟਾ ਕੇ ਉੱ	ದ ೧೯೭೪ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧೯೧೭ ೧	ារ ប្រជាជនជាតិ ។ ស
	-	-		-	)
				-	-	N/A	0
		-		1		に
	1	-		-		+	0
	l	-	1	l		l	।	8	61
	-	-	-	-	る。そのため、その他その他のあなたのです。その他の人気がないないかなかなかなかなかったのです。その他の人気がないということです。その他の人気がない。その他の人気がない。その他の人気がない。その他の人気がない。その他の人気がない。その他の人気がない。その他の人気がない。その他の人気がない。その他の人気がない。その他	N/A	I	0
	-		l	1		ll		l
	l	l	1		==	+
	l		-	1	-			নে	P
	-	VIN VIN	1	-	N/A	-	00 NO Do
	l	ll	-	l	l			6	N
	-		-	-	-	N/A
	=	-	l	-	1		【		ਨ
		t	l	N/A	-	l	0 ທ
	*	-	N/A	l	-	-		p	6
		-	ll			+
			ll
Total							811	હ્વા	્વર્સ

able 1: C. trachomatis Patient- and Clinician-Collected Vaginal Swab Specimen Analysis for Female Patient Infected Statu

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. . .mary of Safety and Effectivene
K032554

N/A = Specimen not obtained or available for testing
= represents equivocal on repeat testing

Represents equivalent on repeat testing

Confidential

Gen-Probe Incorporate

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Summary of Safety and Effectiveness
K032554

Patient InfectedStatus	NAAT 1		NAAT 2 (APTIMA Combo 2 Assay)			APTIMA Combo 2 Assay			Symptom Status
	EndocervicalSwab	Urine	EndocervicalSwab	Urine	Patient-CollectedVaginal Swab	Clinician-CollectedVaginal Swab	Symptomatic	Asymptomatic
Infected	+	+	+	+	+	+	44	15	59
Infected	+	+	+	+	+	+	1	0	1
Infected	+	+	+	+	N/A	+	0	1	1
Infected	+	+	+	+	+	+	1	0	1
Infected	+	+	+	+	+	+	2	2	4
Infected	+	+	+	+	+	+	1	1	2
Infected	+	+	+	+	+	+	1	1	2
Infected	+	+	+	+	+	+	0	1	1
Infected	+	+	+	+	+	+	1	0	1
Infected	+	+	+	+	+	+	5	1	6
Non-infected	+	-	+	-	+	+	1	0	1
Non-infected	+	+	+	+	+	+	5	2	7
Non-infected	+	+	+	+	+	+	0	1	1
Non-infected	+	+	+	+	+	+	2	1	3
Non-infected	+	+	+	+	+	+	2	0	2
Non-infected	+	+	+	+	+	+	2	2	4
Non-infected	-	-	-	-	-	-	698	577	1275
Non-infected	+	N/A	+	N/A	N/A	=	0	2	2
Non-infected	+	N/A	+	N/A	N/A	N/A	15	9	24
Non-infected	+	N/A	+	N/A	N/A	N/A	1	0	1
Non-infected	+	N/A	+	N/A	N/A	N/A	2	2	4
Non-infected	+	N/A	+	N/A	N/A	N/A	11	10	21

Table 2: N. gonorrhoeae Patient- and Clinician-Collected Vaginal Swab Specimen Analysis for Female Patient Infected Statu

Confidentia

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mary of Safety and Effectivenes ﺮ ﺍﻟﻤﺮﺍﺟﻊ ﺍﻟﻤﺴﺎﺣﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍ

2554



03

ਮ

Patient InfectedStatus	NAAT 1		NAAT 2 (APTIMA Combo 2 Assay)			APTIMA Combo 2 Assay		Symptom Status
	EndocervicalSwab	Urine	EndocervicalSwab	Urine	Patient-CollectedVaginal Swab	Clinician-CollectedVaginal Swab	Symptomatic	Asymptomatic
Non-infected	-	=	-	-	-	N/A	0	1	1
Non-infected	=	-	-	-	-	-	1	1	2
Non-infected	-	-	N/A	-	-	-	0	1	1
Non-infected	-	-	-	-	-	N/A	5	4	9
Non-infected	-	-	=	-	-	-	1	1	2
Total							810	640	1450

N/A = Specimen not obtained or available for testing
= represents equivocal on repeat testing

PERSPECTIVES ON
ISSUES IN INTEGRATED
STUDIES

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{16}------------------------------------------------

Summary of Safety and Effectiveness
K032554

Specimer	Symptom Status		TD	FP	TN	FN		Sensiti vity (95% C.I.	Specificity	(95% C.I
Patient-Collected Vaginal Swat	Asymptomatic	288	રહ	। ୧.	રવેવ		08:4	91.5 - 100 (92.8 - 98.8	97.2	(95.4 - 98.4)
	All	423	172	28b	217	9	96.6		97.8	96.8 - 98.5)
inician-Collected Vaginal Swab	Symptomatic	800	113	23°	રવેત	P	તે છે. 6		96.7	(95.1 - 97.9) (96.0 - 98.7) (96.0 - 97.9)
	Asymptomatic	ર 36	61	l Ag	ર રતે	C	તેરૂ જિલ્લામાં આવેલું એક ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે	91.5 - 99.1 189.0 - 99.6 192.9 - 98.8	97.6
		1445		37°	228		96.7		97 l
CT TMA Alternate Amplification results: # positive results/# specimens test
a: 13/16 b: 24/28 c: 15/23 d: 13/14 e: 28/37

ble 3: C. trachomatis Sensitivity and Specificity: APTIMA Combo 2 Assay Vaginal Swab Specimens vs. Patient Infected Statu

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{17}------------------------------------------------

and Effectiveness

Safetyof
.larySL.	K032554

	Table 4: C. trachomatis Performance by Clinical Site: APTIMA Combo 2 Assay Vaginal Swab Specimens vs. Patient Infected Status
Specimen	Site	N	TP	FP	TN	FN	Prev (%)	Sensitivity (95% C.I.)	Specificity (95% C.I.)	PPV (%)	NPV (%)
Patient-CollectedVaginal Swab	1	218	34	6	177	1	16.1	97.1 (85.1 - 99.9)	96.7 (93.0 - 98.8)	85.0	99.4
	2	195	50	6	137	2	26.7	96.2 (86.8 - 99.5)	95.8 (91.1 - 98.4)	89.3	98.6
	3	111	10	1	100	0	9.0	100 (69.2 - 100)	99.0 (94.6 - 100)	90.9	100
	4	261	20	4	236	1	8.0	95.2 (76.2 - 99.9)	98.3 (95.8 - 99.5)	83.3	99.6
	5	199	13	3	183	0	6.5	100 (75.3 - 100)	98.4 (95.4 - 99.7)	81.3	100
	6	290	32	5	251	2	11.7	94.1 (80.3 - 99.3)	98.0 (95.5 - 99.4)	86.5	99.2
	7	102	10	2	90	0	9.8	100 (69.2 - 100)	97.8 (92.4 - 99.7)	83.3	100
	8	47	3	1	43	0	6.4	100 (29.2 - 100)	97.7 (88.0 - 99.9)	75.0	100
	ALL	1423	172	28	1217	6	12.5	96.6 (92.8 - 98.8)	97.8 (96.8 - 98.5)	86.0	99.5
Clinician-CollectedVaginal Swab	1	227	35	8	182	2	16.3	94.6 (81.8 - 99.3)	95.8 (91.9 - 98.2)	81.4	98.9
	2	196	50	5	139	2	26.5	96.2 (86.8 - 99.5)	96.5 (92.1 - 98.9)	90.9	98.6
	3	113	10	2	101	0	8.8	100 (69.2 - 100)	98.1 (93.2 - 99.8)	83.3	100
	4	262	20	10	231	1	8.0	95.2 (76.2 - 99.9)	95.9 (92.5 - 98.0)	66.7	99.6
	5	199	13	2	184	0	6.5	100 (75.3 - 100)	98.9 (96.2 - 99.9)	86.7	100
	6	296	34	8	254	0	11.5	100 (89.7 - 100)	96.9 (94.1 - 98.7)	81.0	100
	7	102	9	1	91	1	9.8	90.0 (55.5 - 99.7)	98.9 (94.1 - 100)	90.0	98.9
	8	50	3	1	46	0	6.0	100 (29.2 - 100)	97.9 (88.7 - 99.9)	75.0	100
	ALL	1445	174	37	1228	6	12.5	96.7 (92.9 - 98.8)	97.1 (96.0 - 97.9)	82.5	99.5

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Gen-Probe Incorporated

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Status
-


Property



1
1
Vaginal Swab Specimens vs. Patient Infected Status------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
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and and and and and the commend of the commend of the commend of the comments of the first and the mail of the first and the first and the former the former the forme the for
Specimer	Symptom Status	N	1 LTT	FP	TN	FN	Sensitivity	95% C.I.	specificit	95% C.I.
Patient-Collected Vaginal Swab	Asymptomatic	659	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------22	くなখ	୧୦ર		100	10084.6 -	99.7	100198.8 -
	All	423	76	ep	340		98.7	10093.0 -	99.6	99.0 - 99.8
'linician-Collected Vaginal Swab Symptomatic		807	ਟ ਤੇ	ર્દ ૮	747	1	96.4	તેત્વે છ87.5 - .	99.3	98.5 - 99.8)
	Asymptomatic	637	22	p &	QII		વેરે 7	78.1 - 99.9,	વેત્તે રે	98.6 - 99.9
	Al	444	75	8	.358		96.2	89.2 - 99.2	99.4	98.8 - 99.7
(1) Marte Alexanda Amerificantian maultar # manimano rach

'GC TMA Alternate Amplification results: # positive results/# specimens tested
a: 2/2 b: 6/6 c: 5/5 d: 2/3 e: 7/8

28.66.55.22.33.7

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{19}------------------------------------------------

able 6: N. gonorrhoeae Performance by Clinical Site: APTIMA Combo 2 Assay Vaginal Swab Specimens vs. Patient Infected Stati

Specime	Site	N	TP	FP	TN	FN	Prev (%)	Sensitivity	(95% C.I.)	Specificity	(95% C.I.)	PPV	NPV
												(%)	(%)
		217	I 3		203			92.9	ರಿಗೆ ಕೆಳಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರ्२० ।	100
atient-Collect aginal Swab	C	ો તેર			164	-00000000		100		ಕ್ಷಣ ಸಿಕ್ಷಣ ಸ್ಥಳದ ಪ್ರತಿ ಸ್ಥೆಗಳು ಸೇರಿ ಸೇರಿ ಸೇರಿ ಸೇರಿ ಸೇರಿ ಸ		일 중 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공 공	್ದ ಕ್ಷತ್ರ ಕ್ರಿ ಕೃತ ಕೃತ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ರಿ ಕ್ಷಿತ್ರ ಪ್ರಸಿ
	ದ							100
		261						100
	S	I dd						100
	9			-----------	ទ្ធសន្ធមាន ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នោះ ១៩ នាក់ ១៩ នាក់ ១៩ នាក់ ១៩ នា				ള്ള ജ്വീട്ടില്ല് ജീവിച്ചിരിച്ചു. അവലംബം വേട്ടി ജീവിച്ച വിവ
		201 067						1/11 00 T
		47						1001
	ALL	1423	14 4 6 0 0 0 0 0 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1 2 6 1		340	โ	ហូតមួយ ១០០០ ដក		001 10011 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1 - 1		ക്രിക്കുന്നത്. അവലംബം അവലംബം പ്രവർത്തിച്ചു. അവലംബം കുറച്ചു വിവരുന്നു വാഹ്യത്തിൽ നിന്നും വിശ്വാസ്ത്രിക്കുന്നു. അവലംബം അവലംബം അവലംബം

nician-Collec		227						100	100	100
aginal Swa								100
	ర్లాల							75.0	6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6- $61. - 88.8.8 - 78.82
	P							100	100)
	S							100	100(47.8 - 15.8 -	റ്റും ഉപ്പുഴി സംഭവ ഗ്ഗങ്ങളുടെ ഭാഗം ഗ്ഗങ്ങളുടെ ഭ	001 1666 (001 6666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666666	ತ್ತಿದ್ದ ಸ್ನೇಶ್ವಿ ಪ್ರಶಸ್ತಿ ಶ್ವಿತ್ವ	ತ ಕ್ರಿ ಪ್ಲೆ ಶ್ವಿತ ಶ್ವಿ ಶ್ವಿ ಶ್ವಿ ಶ್ವಿ ಶ್ವಿ ಶ್ರೀ ಶೇಖ
	9									001 901 9186	99.6)
	1										001
		ន គួរ និង និង និង ន	7 – 68 – 68 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 – 2 –	000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000	កម្ពុជា និងប្រជាជនជាតិ	00-0000000	ស់ ហុស្សនា ១០០ នាក់ ប្រជាជន ប្រជាជន ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជាជន និង ប្រជា	ារ សារ លោក	68.3 - 98.8)		តែ និង និង និង និង ន
	ALL	444						96.2		99.4	98.8 - 99.7	90.4	ర్తి 8

Confidentia

Gen-Probe Incorporate

{20}------------------------------------------------

Prevalence

The prevalence of C. trachomatis and/or N. gonorrhoeae disease in patient populations depends on risk factors such as age, gender, the presence of symptoms, the type of clinic, and the test method. A summary of the prevalence of three C. trachomatis and N. gonorrhoeae disease outcomes as determined by the APTIMA Combo 2 Assay is shown in Table 7 for the vaginal swab specimen multi-center clinical study by clinical site and overall.

Confidential

{21}------------------------------------------------

Summary of Safety and Effectiveness
K032554

Site	Patient-Collected Vaginal Swab, % Prevalence (# positive/# tested)			Clinician-Collected Vaginal Swab, % Prevalence (# positive/# tested)
	CT+/GC+	CT+/GC-	CT-/GC+	CT+/GC+	CT+/GC-	CT-/GC+
1	1.8(4/220)	16.4(36/220)	4.1(9/220)	3(7/230)	15.7(36/230)	3.5(8/230)
2	9.6(19/198)	18.7(37/198)	6.6(13/198)	9.5(19/199)	18.1(36/199)	7(14/199)
3	0.9(1/111)	9(10/111)	2.7(3/111)	0.9(1/113)	9.7(11/113)	1.8(2/113)
4	0.4(1/266)	9(24/266)	1.9(5/266)	0.4(1/267)	11.2(30/267)	2.2(6/267)
5	0.5(1/199)	7.5(15/199)	0.5(1/199)	0.5(1/199)	7(14/199)	0.5(1/199)
6	2.8(8/290)	10(29/290)	5.5(16/290)	2(6/296)	12.2(36/296)	5.4(16/296)
7	0(0/102)	11.8(12/102)	0(0/102)	0(0/102)	9.8(10/102)	0(0/102)
8	0(0/48)	8.3(4/48)	2.1(1/48)	0(0/51)	7.8(4/51)	2(1/51)
All	2.4(34/1434)	11.6(167/1434)	3.3(48/1434)	2.4(35/1457)	12.1(177/1457)	3.3(48/1457)

Table 7: Prevalence of C. trachomatis and/or N. gonorrhoeae Disease as Deternined by the APTIMA Combo 2 Assay Results by Clinical Site

Gen-Probe Incorporate

{22}------------------------------------------------

Positive and Negative Predictive Values for Hypothetical Prevalence Rates

The estimated positive and negative predictive values (PPV and NPV) for different hypothetical prevalence rates using the APTIMA Combo 2 Assay are shown in Tables 8 and 9 for C. trachomatis and N. gonorrhoeae, respectively. These calculations are based on a hypothetical prevalence and the overall sensitivity and specificity calculated from the patient infected status for two multi-center clinical studies; the endocervical swab, male urethral swab, and urine specimen clinical study and the vaginal swab specimen clinical study. The overall sensitivity and specificity for C. trachomatis was 96.1% and 97.9%, respectively (Table 8). The overall sensitivity and specificity for N. gonorrhoeve was 98.0% and 99.1%, respectively (Table 9). The actual PPV and NPV calculated using the clinical study data are shown in Tables 4 and 6 for C. trachomatis and N. gonorrhoeae, respectively

Table 8: Positive and Negative Predictive Values for Hypothetical Prevalence Rates- C. trachomatis

Prevalence Rate (%)	Sensitivity (%)	Specificity (%)	Positive PredictiveValue (%)	Negative PredictiveValue (%)
2	95.9	98.2	52.1	99.9
5	95.9	98.2	73.7	99.8
10	95.9	98.2	85.5	99.5
15	95.9	98.2	90.4	99.3
20	95.9	98.2	93.0	99.0
25	95.9	98.2	94.7	98.6
30	95.9	98.2	95.8	98.2

Table 9: Positive and Negative Values for Hypothetical Prevalence Rates- N. gonorrhoeae

Prevalence Rate (%)	Sensitivity (%)	Specificity (%)	Positive PredictiveValue (%)	Negative PredictiveValue (%)
2	97.8	98.9	64.5	100
5	97.8	98.9	82.4	99.9
10	97.8	98.9	90.8	99.8
15	97.8	98.9	94.0	99.6
20	97.8	98.9	95.7	99.4
25	97.8	98.9	96.7	99.3
30	97.8	98.9	97.4	99.1

{23}------------------------------------------------

Assay Control Performance

Control RLU data were generated as part of the vaginal swab specimen clinical study. A summary of the APTIMA Positive Control, CT/Negative Control, GC and APTIMA Positive Control, GC/Negative Control, CT performance during the clinical study is presented in Table 10.

Control	Statistics	Total RLU (x1000)
Positive, CT/Negative, GC	Maximum	1996
	75th Percentile	1279
	Median	1135
	25th Percentile	933
	Minimum	174
Positive, GC/Negative, CT	Maximum	1420
	75th Percentile	1255
	Median	1169
	25th Percentile	1084
	Minimum	249

Table 10: Distribution of Total RLU of the APTIMA Assay Controls from the Vaginal Swab Specimen Clinical Study

{24}------------------------------------------------

Conclusions from the Clinical Data

The non-clinical and clinical study results support the use of clinician-collected and patient-collected vaginal swab specimens in the GEN-PROBE APTIMA Combo 2 Assay for the detection of C. trachomatis and N. gonorrhoeae. The GEN-PROBE APTIMA Vaginal Swab Specimen Collection Kit provides the necessary materials to allow for the testing of clinician-collected or patient-collected vaginal specimens in the APTIMA Combo 2 Assay. Use of this ancillary kit broadens the application of the APTMA Combo 2 Assay as a diagnostic tool to provide information that measurably contributes to a diagnosis of C. trachomatis and N. gonorrhoeae infection.

The results of the clinical study demonstrate reasonable evidence that when the APTIMA Combo 2 Assay and the APTIMA Vaginal Swab Specimen Collection Kit are labeled as proposed, the GEN-PROBE APTIMA Combo 2 Assay is safe and effective for its stated intended use.

Application of the APTIMA Vaginal Swab Specimen Collection kit in the APTIMA Combo 2 Assay provides performance that is substantially equivalent to that of the previously cleared claims (K003395) for the detection of C. trachomatis and N. gonorrhoeae which is indicative of it's safety and effectiveness.

Contraindications and Cautions

There are no contraindications or cautions.

{25}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/25/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized symbol resembling three overlapping lines, with the bottom line having a wavy appearance. The symbol is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA", which is arranged in a circular fashion around the symbol.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 3 1 2003

Alan Maderazo, Ph.D. RAC Regulatory Affairs Specialist Gen-Probe Incorporated 10210 Genetic Center Drive San Diego, CA 92121-1589

Re: K032554

Trade/Device Name: GEN-PROBE® APTIMA® Combo 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: December 24, 2003 Received: December 29, 2003

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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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). Other general information on your responsibilities under the Act may be obtained 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,

Steven Putman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

K032554 510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name:

GEN-PROBE® APTIMA® Combo 2 Assay

Indications for Use (AC2 Assay package insert):

*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.

Indications for Use (Ancillary Kit package insert):

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)

Saqartzonl 12/31/03

Division Sien-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k)_K0325554

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).