The Simple 2 Test is intended for in vitro detection and identification of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) in home-collected specimens which are shipped to a clinical laboratory for testing using the Aptima Combo 2 Assay on the Panther System. This product is available over-the-counter (OTC) to consumers 18 years of age and older.

The Simple 2 Test contains all the necessary components to collect urine from male patients (Simple 2 Urine Home Collection Kit (Penile)) or vaginal swabs from female patients (Simple 2 Swab Home Collection Kit (Vaginal)) in their home, or in similar environments, without supervision from a healthcare provider.

The Simple 2 Test Collection Kits may also be used to self-collect specimens in a clinic.

The testing is performed, as determined to be appropriate, based on the results of LetsGetChecked Suitability Questionnaire.

This test system is not a substitute for visits to a healthcare provider. The information provided by this product should not be used to start, stop, or change any course of treatment unless advised by your healthcare provider.

Testing is limited to the manufacturer, Priva Path laboratories (d.b.a. LetsGetChecked. Inc.).

Device Description

The LetsGetChecked Simple 2 Test is composed of the Simple 2 Urine Home Collection Kit (Penile) and the Simple 2 Swab Home Collection Kit (Vaginal) and the samples are shipped to LetsGetChecked's Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory for processing using the Aptima Combo 2 Assay on the Panther System. The Aptima Combo 2 Assay was previously cleared for the qualitative in vitro detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) when used with male urine and self-collected vaginal swabs collected in clinical settings.

The home collection kits are intended to be distributed for purchase online without the need for prescription from a physician or healthcare professional (over-the-counter use). After purchase, the user activates the kit on LetsGetChecked's website and is requested to fill out the Suitability Questionnaire to determine whether this test is appropriate for this individual. The user follows detailed directions for self-collecting a urogenital specimen (male urine or female vaginal swab, as applicable), packaging and shipping it to the LetsGetChecked CLIA certified laboratory for testing (PrivaPath lab). The test results are delivered to the individual via LetsGetChecked online portal. Positive and invalid/inconclusive results are followed up with a call from the LetsGetChecked Care Team. If the patient received a positive chlamydia result, treatment options are discussed. Patients receiving a positive gonorrhea test result, will be advised to contact their healthcare provider to receive appropriate treatment. The LetsGetChecked Care Team will also contact all patients who test negative for chlamydia and gonorrhea, but do report symptoms, or concerns, or where further investigation is indicated. These patients are internally flagged for follow-up.

AI/ML Overview

The provided text describes the evaluation of the Simple 2 Test, a device for the in vitro detection and identification of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) in home-collected specimens. The device is intended for over-the-counter use by consumers 18 years of age and older.

The acceptance criteria for the device are focused on usability and comprehension by lay users and the analytical performance of the collection kits under various challenging conditions (flex studies, interfering substances, shipping stability), ensuring that the home collection process does not compromise the accuracy of the downstream testing performed by the Aptima Combo 2 Assay on the Panther System.

Here's a breakdown of the requested information based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a single table outlining predefined "acceptance criteria" alongside specific performance metrics the device must meet. Instead, it describes various studies and their outcomes, implicitly demonstrating the device's acceptable performance. The "Success Rate" shown in Tables 3, 4, 7, and 8 for usability/comprehension, and the "Agreement with expected result" in Tables 9, 10, 11, 12, 13, 14, 16, 18, 19, and 20 for analytical performance, serve as the evidence of meeting the unstated acceptance goals.

Based on the summaries of the studies, the implicit acceptance criterion for usability and comprehension appears to be a high success rate (generally aiming for 100% in critical steps or demonstrating that modifications resolve issues) for proper specimen collection, packaging, and comprehension of instructions and results. For analytical performance, the criterion is largely 100% agreement with expected results under various challenging conditions, or demonstration that the test robustly performs within acceptable limits despite certain challenging conditions, with any identified limitations clearly called out in labeling.

Implicit Acceptance Criteria and Reported Performance (Selected examples from the document):

Category	Study/Parameter	Implicit Acceptance Criteria (Goal)	Reported Device Performance (Key Findings)
Usability & Comprehension (Male Urine Kit)	Ability to transfer correct urine volume (after modification)	High success rate	"The results from this study showed that 9% (8/89) of lay users had difficulty transferring correct volume of urine... Therefore, modifications to the home collection kit and instructions were necessary..." (Initial study). Modifications made: graduated transfer pipette and revised instructions. The second study's "Success Rate" for various steps indicates high user compliance, though exact percentage for volume transfer is redacted in Table 3. The text states: "replacing generic transfer pipette with the graduated transfer pipette allows the users to transfer an appropriate amount of urine..."
	Comprehension of IFU, warnings, and general info	High success rate	Data redacted in Table 3, but the text states: "...results from the questionnaire support the conclusion that lay users demonstrated comprehension of the critical elements in the labeling..."
Usability & Comprehension (Female Vaginal Swab Kit)	Ease of use of collection kit	High success rate	Initial study led to modifications for closer alignment with Hologic's instructions and FAQs. Success rates for various steps are redacted in Table 7, but the text states: "...results from the questionnaire support the conclusion that lay users demonstrated comprehension of the critical elements in the labeling..."
Flex Studies (Urine Kit - Underfilled Tubes)	CT/GC detection at LoD with varying urine volumes	100% agreement with expected results (or robust performance within acceptable limits)	CT: 100% agreement when at least [b-4] of urine transferred; 80% at lower volumes. GC: 100% agreement when at least [b-4] of urine transferred; 60% at lower volumes. The conclusion states: "...underfilling the Transport Tube with urine will generate accurate results if at least [b-4] of the specified volume) of urine is transferred."
Flex Studies (Urine Kit - Overfilled Tubes)	CT/GC detection at LoD with varying urine volumes	100% agreement with expected results	CT/GC: 100% agreement across all tested overfilled volumes (Table 10). The conclusion states: "The results also showed that the test is not sensitive to overfilling the Transport Tube."
Flex Studies (Urine Kit - Delay of Urine Transfer)	CT/GC detection at LoD with delay in transfer	100% agreement until specified delay limit	CT: 100% agreement up to 6 days, then drops to 60% at Week 3. GC: 100% agreement up to 1 day, then drops to 0% at 2 days. The conclusion states: "False negative results for CT were obtained when the urine was transferred... three weeks... False negative results were obtained for GC when the transfer of urine... was delayed more than one day." Mitigation: IFU directs immediate transfer and same-day shipping.
Interfering Substances (Urine Kit)	CT/GC detection at LoD in presence of contaminants	100% agreement with expected results	CT: 100% agreement with all substances. GC: False negatives obtained with certain brands of hand soap (0% and 67%) and hand sanitizer (50%). Mitigation: Labeling cautions and instructions to wash/dry hands.
Interfering Substances (Vaginal Swab Kit)	CT/GC detection at LoD in presence of contaminants	100% agreement with expected results	CT/GC: 100% agreement with all substances (Table 14).
Shipping Stability (Urine Kit - Summer/Winter)	CT/GC detection at LoD after exposure to extreme temperatures	Maintain sample integrity allowing for expected results (>95% positivity at LoD)	Summer: 100% positive for both CT/GC. Winter: [b-4] positive for CT, [b-4] positive for GC. The conclusion states: "The data demonstrate that the urine sample integrity is maintained even when exposed to extremes of temperature during shipping." Acceptable as >95% positive at LoD when a certain (redacted) number of samples were tested.
Shipping Stability (Vaginal Swab Kit - Summer/Winter)	CT/GC detection at LoD after exposure to extreme temperatures	Maintain sample integrity allowing for expected results	Summer/Winter: 100% positive for both CT/GC. The conclusion states: "The study results demonstrate that the vaginal swab sample integrity is maintained even when exposed to extremes of temperature during shipping."

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

The test sets are primarily derived from usability and analytical performance studies.

Usability Studies (Test Set):
- Simple 2 Urine Home Collection Kit (Penile):
  - Initial study: 89 male participants.
  - Final usability study: 32 male participants.
- Simple 2 Swab Home Collection Kit (Vaginal):
  - Initial study: 85 female participants.
  - Final usability study: 34 participants (33 female, 1 transgender male).
- Data Provenance: The studies were conducted remotely from lay users' homes via online video conferencing. No specific country of origin is mentioned beyond being a US FDA submission, implying the studies were conducted in the US or for the US market. The studies appear to be prospective in nature, as they involve participants actively performing tasks following instructions and providing feedback/data.
Analytical Performance Studies (Flex, Interfering Substances, Shipping Stability - Test Set):
- These studies involved specific numbers of replicates for each condition (e.g., [b-4] positive and [b-4] negative replicates for flex studies on urine volume). The exact total sample sizes for these analytical tests are scattered across tables with redacted information (e.g., "[b-4] positives/[b-4] tested").
- Data Provenance: These are laboratory-based analytical studies, not human clinical trials. The data provenance is internal to the manufacturer's testing or a clinical laboratory. No specific country of origin is stated, but given the FDA submission, the data is expected to be relevant to US regulatory standards. These are experimental evaluations, likely prospective in nature within a controlled lab setting, designed to mimic real-world conditions.

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

Usability Studies: Ground truth for these studies was generally based on the objective observation of successful completion of tasks (e.g., transferring correct urine volume, proper packaging) and comprehension of instructions/information as assessed by study staff questions. The document does not specify the number or qualifications of experts involved in observing or assessing these lay user interactions directly. However, the design of the modifications and the evaluation criteria would have been informed by regulatory requirements and potentially human factors experts.
Analytical Performance Studies: For these studies, the ground truth is the expected presence or absence of CT/GC in the spiked or unspiked samples. This is a scientific, laboratory-defined ground truth, established by the precise spiking of organisms at known concentrations into negative matrices or using truly negative samples. The "experts" in this context are the laboratory scientists and technicians conducting the assays and preparing the samples, presumed to be qualified in molecular diagnostics. No specific number or external qualifications are mentioned for establishing this analytical ground truth, as it's inherent to the experimental design (e.g., "spiked with CT or GC organisms at the target concentration of LoD").

4. Adjudication Method for the Test Set

Usability Studies: The success/failure of user actions and comprehension was likely determined by the study staff observing and questioning participants. The document doesn't detail a formal "adjudication" process akin to expert reader consensus, but rather a direct assessment of task completion and questionnaire responses. Issues identified (e.g., difficulty transferring urine) led to design modifications, implying an iterative evaluation process rather than a strict adjudication of initial failures.
Analytical Performance Studies: The results (e.g., #positives/#tested, agreement with expected result) are quantitative outcomes of the biochemical assay. There is no mention of an "adjudication method" in the sense of multiple human experts reviewing results. The expectation is that the laboratory results directly represent the device's performance under the tested conditions.

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

There is no mention (and no indication) of a Multi-Reader Multi-Case (MRMC) comparative effectiveness study involving human readers with and without AI assistance. This device is not an AI-assisted diagnostic. It is a home collection kit for a laboratory test, wherein the "device" is the collection system and the final analysis is done by an established IVD system (Aptima Combo 2 Assay on the Panther System). The studies focus on the usability and analytical integrity of the home-collected samples, not on AI-assisted interpretation of diagnostic images or data.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

This question is Not Applicable in the context of this device. The Simple 2 Test is a collection kit, not a standalone algorithm. The "algorithm" (nucleic acid amplification assay) is the Aptima Combo 2 Assay on the Panther System, which is a pre-existing cleared/approved device. The performance data presented relates to the integrity and suitability of the home-collected samples for use with that established assay, not a novel standalone algorithm.

7. Type of Ground Truth Used

Usability Studies: The ground truth for these studies was the observed proper execution of instructed tasks and comprehension of information by lay users, assessed against predefined criteria for successful use of the collection kit and understanding of the accompanying materials.
Analytical Performance Studies: The ground truth was analytically established through precise spiking of known concentrations of CT and GC organisms into negative matrices, or the use of confirmed negative samples. This constitutes a laboratory-defined ground truth (e.g., "spiked with GC or CT at 3x LoD").

8. Sample Size for the Training Set

The document describes two phases of usability/comprehension studies (initial and final) for both the urine and vaginal swab kits. The initial studies for both kits served a similar function to a training set or preliminary evaluation, leading to modifications in the kit and instructions.

Simple 2 Urine Home Collection Kit (Penile): 89 male participants in the initial study.
Simple 2 Swab Home Collection Kit (Vaginal): 85 female participants in the initial study.
These initial studies acted as "training" or optimization phases by identifying deficiencies that informed product improvements.

For the analytical "flex studies, interfering substances, and shipping stability" tests, the concept of a "training set" is not applicable in the typical machine learning sense. These are experimental validations. The initial LoD (Limit of Detection) establishment, mentioned briefly, might involve some preliminary testing that could be seen as "training" for setting analytical parameters, but no specific sample size for such an activity is provided.

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

For the usability studies, the ground truth for the initial "training" phase was based on direct observation of user performance and comprehension assessments, identifying areas where users struggled or misunderstood. For example, the 9% of users having difficulty transferring urine volume in the initial penile kit usability study highlighted a deficiency that needed to be addressed. This identified "ground truth" (i.e., areas of user error) then informed the modifications.

For the analytical studies, as noted in point 7, ground truth is laboratory-defined by precise manipulation of samples (e.g., spiking with known concentrations, ensuring negative samples are truly negative). This analytical ground truth would be established through standard laboratory and molecular biology techniques.

Summary

{0}------------------------------------------------

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: a symbol on the left and the text "FDA U.S. FOOD & DRUG ADMINISTRATION" on the right. The symbol is a stylized representation of a caduceus, a traditional symbol of medicine. The text is written in a clear, sans-serif font, with "FDA" in a blue box.

EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR Simple 2 Test DECISION SUMMARY

I Background Information:

A De Novo Number
DEN200070

B Applicant

LetsGetChecked Inc. (formerly PrivaPath Diagnostics Inc.)

C Proprietary and Established Names

Simple 2 Test

D Regulatory Information

ProductCode(s)	Classification	RegulationSection	Panel
QYA	Class II	21 CFR 866.3385 - System for detection ofnucleic acid from non-viral microorganism(s)causing sexually transmitted infections usinghome-collected specimens	MI - Microbiology

Submission/Device Overview: II

A Purpose for Submission:

De Novo request for evaluation of automatic class III designation for the Simple 2 Test.

B Measurand:

Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) ribosomal RNA (rRNA)

C Type of Test:

Nucleic acid amplification assay

III Indications for Use:

A Intended Use(s):

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov

{1}------------------------------------------------

See Indications for Use below.

B Indication(s) for Use:

The Simple 2 Test Collection Kits may also be used to self-collect specimens in a clinic.

The testing is performed, as determined to be appropriate, based on the results of LetsGetChecked Suitability Questionnaire.

Testing is limited to the manufacturer, Priva Path laboratories (d.b.a. LetsGetChecked. Inc.).

C Special Conditions for Use Statement(s):

OTC - Over the Counter

D Special Instrument Requirements:

Panther System

IV Device/System Characteristics:

A Device Description:

{2}------------------------------------------------

as applicable), packaging and shipping it to the LetsGetChecked CLIA certified laboratory for testing (PrivaPath lab). The test results are delivered to the individual via LetsGetChecked online portal. Positive and invalid/inconclusive results are followed up with a call from the LetsGetChecked Care Team. If the patient received a positive chlamydia result, treatment options are discussed. Patients receiving a positive gonorrhea test result, will be advised to contact their healthcare provider to receive appropriate treatment. The LetsGetChecked Care Team will also contact all patients who test negative for chlamydia and gonorrhea, but do report symptoms, or concerns, or where further investigation is indicated. These patients are internally flagged for follow-up.

Simple 2 Urine Home Collection Kit (Penile)

Each Simple 2 Urine Home Collection Kit (Penile) includes a urine collection cup with indicated urine fill area, one Aptima Urine Specimen Transport Tube, a graduated transfer pipette, a biohazard bag, home specimen collection and shipping instructions, and Frequently Asked Questions (FAQs) sheets with information about CT/GC infections and test results. All components are included in the box which is also used for shipping of the sample to the laboratory for testing.

Simple 2 Swab Home Collection Kit (Vaginal)

Each Simple 2 Swab Home Collection Kit (Vaginal) includes Aptima Multitest Swab Specimen Collection Kit, which includes sterile vaginal swab and Sample Transport Tube. The kit also includes a biohazard bag, home specimen collection and shipping instructions, and Frequently Asked Questions (FAQs) sheets with information about CT/GC infections and test results. All components are included in the box which is also used for shipping of the sample to the laboratory for testing.

B Principle of Operation

The Aptima Combo 2 Assay utilizes target capture, transcription-mediated amplification, hybridization protection assay, and dual kinetic assay for specimen processing to amplify target rRNA and detect the amplicon, respectively. Please refer to the decision summaries of K111409, K132251, K180681, and K200866.

C Instrument Description Information

1. Instrument Name:
  Panther System
1. Specimen Identification:
  Refer to K111409, K132251, K180681, and K200866
1. Specimen Sampling and Handling:
  Refer to K111409, K132251, K180681, and K200866
1. Calibration:

{3}------------------------------------------------

Refer to K111409, K132251, K180681, and K200866

1. Quality Control:
  Refer to K111409, K132251, K180681, and K200866

V Standards/Guidance Documents Referenced:

Not applicable.

VI Performance Characteristics:

A Analytical Performance:

1. Precision/Reproducibility:
  Reproducibility and within laboratory precision studies were previously reviewed and described in K111409, K132251, K180681, and K200866.
1. Linearity:
  Not Applicable; this is a qualitative assay.
1. Analytical Specificity/Interference:
  Analytical Specificity/Interference studies were previously reviewed and described in K111409, K132251, K180681, and K200866.
1. Assay Reportable Range:
  Not Applicable; this is a qualitative assay.
1. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
  Traceability, Stability, Expected Values (Controls, Calibrators, or Methods) were previously reviewed and described in K111409, K132251, K180681, and K200866.
1. Detection Limit:
  The Detection Limit was previously reviewed and described in K111409, K132251, K180681, and K200866.
1. Assay Cut-Off:
  Assay cut-off was previously reviewed and described in K111409, K132251, K180681, and K200866.

{4}------------------------------------------------

8. Accuracy (Instrument):

Instrument accuracy was previously reviewed and described in K111409, K132251, K180681, and K200866.

1. Carry-Over:
  Carry-Over study was previously reviewed and described in K111409, K132251, K180681, and K200866.

B Comparison Studies:

1. Method Comparison:
  Not applicable.
1. Matrix Comparison:
  Not applicable.

C Clinical Studies:

1. Clinical Sensitivity:
  Clinical Sensitivity was previously reviewed and described in K111409, K132251, K180681, and K200866.
1. Clinical Specificity:
  Clinical Specificity was previously reviewed and described in K111409, K132251, K180681, and K200866.
1. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
  Not applicable.

D Clinical Cut-Off:

Not applicable.

Expected Values/Reference Range: E .

Expected Values/Reference Range was previously reviewed and described in K111409, K132251, K180681, and K200866.

F Other Supportive Performance Characteristics Data:

1. USABILITY AND COMPREHENSION

{5}------------------------------------------------

A. Simple 2 Urine Home Collection Kit (Penile)

Two usability and comprehension studies with lay users were conducted to evaluate the ease of use of the collection kit, ability to interpret the test results and comprehension of the educational materials included in the Simple 2 Urine Home Collection Kit (Penile). The first study was conducted with 89 male participants. The summary of demographics of participants included in this study is presented in Table 1.

Participants	N	%
Male	89	100%
Age Group
18-25	7	8%
26-35	25	28%
36-45	17	19%
46-55	20	22%
56-65	14	16%
> 65	6	7%
Education
< High school	0	0%
High school/Some College	42	47%
Bachelor's degree or higher	47	53%
Race/Ethnicity
Caucasian	55	62%
Asian	7	8%
Hispanic/Latin American	9	10%
Black/African American	11	12%
Mixed/Unknown/Other	7	8%

Table 1. Summary of Demographics of Participants in the Initial Usability and Comprehension Study for the Simple 2 Urine Home Collection Kit (Penile).

The results from this study showed that 9% (8/89) of lay users had difficulty transferring correct volume of urine to the transport tube. Therefore, modifications to the home collection kit and instructions were necessary and to mitigate the risk of users transferring incorrect volume of urine to the transfer tubes, the collection kit was modified to include a graduated transfer pipette and revisions were made to the instructions on how to transfer the proper volume of urine. In addition, FAQs sheets were added to the kit to help the lay user with understating of test results and to provide educational information on CT/GC infections. To evaluate the modifications introduced to Simple 2 Urine Home Collection Kit (Penile), the second usability and comprehension study was conducted. The summary of demographics of participants in the final usability and comprehension study for the Simple 2 Urine Home Collection Kit (Penile) is presented in Table 2.

{6}------------------------------------------------

activation, sample preparation and packaging, and sample shipment. Participants had an option to watch the instructional video. The lay users did not have to collect a urine sample. In this study, the collection cup was filled with water to simulate urine and evaluate users' ability to transfer the appropriate volume of liquid to the transport tube. After packaging of the sample, the study participants answered study staff questions to evaluate comprehension of the instructions/safety warnings, possible test results, and general information about the diseases. In addition, the samples were evaluated at the testing laboratory for critical errors that could lead to inaccurate test results or sample rejection upon receipt in the laboratory. The results from the study are summarized in the Table 3 and Table 4.

Participants	N	%
Male	32	100
Age Group
18-25	5	16%
26-35	10	31%
36-45	6	19%
46-55	3	9%
56-65	5	16%
> 65	3	9%
Education
< High school	1	3%
High school diploma	4	13%
Some college/AssociatesDegree/Vocational Degree	11	34%
Bachelor's degree	12	38%
Graduate degree	4	13%
Literacy (SAHL)a)
Low (<14)	0	0%
Average (15-16)	2	6%
High (17-18)	30	94%
Race/Ethnicity
Caucasian	15	47%
Asian	2	6%
Hispanic/Latin American	8	25%
Black/African American	3	9%
Mixed/Unknown/Other	3	9%

Table 2. Summary of Demographics of Participants in the Final Usability and Comprehension Study for the Simple 2 Urine Home Collection Kit (Penile).

a) Short Assessment of Health Literacy

Table 3. Summary of Results of Usability and Comprehension Study for the Simple 2 Urine Home Collection Kit (Penile).

Instructions Step/Question	CorrectAction/Response	Success Rate
----------------------------	----------------------------	--------------

{7}------------------------------------------------

Sample Collection Assessment
	(D)(4)









IFU and Warnings Comprehension	(b)(4)

{8}------------------------------------------------

	(D(4)









General Information about Diseases Comprehension

	10(4)

		Success Rate
	(b)(4)
Rejection Reason:
	(b)(4)
N/A Not applicable

N/A Not applicable.

B. Simple 2 Swab Home Collection Kit (Vaginal)

Two usability and comprehension studies with lay users were conducted to evaluate the ease of use, results comprehension, and understanding of the educational materials about

{9}------------------------------------------------

gonorrhea and chlamydia included in the Simple 2 Swab Home Collection Kit (Vaginal). First study was conducted with 85 female participants. The summary of demographics of participants included in this study is presented in Table 5.

Participants	N	%
Female	85	100%
Age Group
18-25	17	20%
26-35	34	40%
36-45	14	16%
46-55	15	18%
56-65	4	5%
> 65	1	1%
Education
< High school	2	2%
High school/Some College	49	58%
Bachelor's degree or higher	34	40%
Race/Ethnicity
Caucasian	44	52%
Asian	7	8%
Hispanic/Latin American	14	16%
Black/African American	14	16%
Mixed/Unknown/Other	6	7%

Table 5. Summary of Demographics of Participants in the Initial Usability and Comprehension Study for the Simple 2 Swab Home Collection Kit (Vaginal).

Upon completion of the study the home collection kit instructions were modified to ensure closer alignment with the instructions from the Hologic's Aptima Multitest Swab Specimen Collection Kit for Patient Collected Specimen. In addition, FAQs sheets were added to the home collection kit to help the lay user with understating of test results and provide education on CT/GC infections. The second usability and comprehension study was conducted to evaluate the modifications introduced to the Simple 2 Swab Home Collection Kit (Vaginal). The summary of demographics of participants in the final usability and comprehension study is presented in Table 6.

Similar to the first study, the second usability and comprehension study was conducted remotely from lay user's home via online video conferencing. The study participants were asked to follow the Instructions for Use provided with the kit to complete tasks required for use of the Simple 2 Swab Home Collection Kit (Vaginal), including kit activation, sample preparation and packaging, and sample shipment. Participants had an option to watch the instructional video. After packaging of the sample, the study participants answered study staff questions to evaluate comprehension of the instructions/safety warnings, possible test results, and general information about the diseases. In addition, the samples were evaluated at the testing laboratory for critical errors that could lead to inaccurate test results or sample

{10}------------------------------------------------

rejection upon shipping. The results from the study are summarized in the Table 7 and Table 8.

Participants	N	%
Female	33	97%
Transgender Male*	1	3%
Age Group
18-25	5	15%
26-35	8	24%
36-45	8	24%
46-55	9	26%
56-65	3	9%
> 65	1	3%
Education
< High school	1	3%
High school diploma	6	18%
Some college/Associates Degree/Vocational Degree	15	44%
Bachelor's degree	10	29%
Graduate degree	2	6%
Literacy (SAHL)a)
Low (&lt14)	2	6%
Average (15-16)	6	18%
High (17-18)	26	77%
Race/Ethnicity
Caucasian	15	44%
Asian	3	9%
Hispanic/Latin American	5	15%
Black/African American	9	26%
Mixed/Unknown/Other	2	6%

Table 6. Summary of Demographics of Participants in the Final Usability and Comprehension Study for the Simple 2 Swab Home Collection Kit (Vaginal).

Short Assessment of Health Literacy a)

Table 7. Summary of Results of Usability and Comprehension Study for the Simple 2 Swab Home Collection Kit (Vaginal).

Instructions Step/Question	CorrectAction/Response	Success Rate
Sample Collection Assessment
(b)(4)

{11}------------------------------------------------

	(DG)





IFU and Warnings Comprehension
	(0)143

{12}------------------------------------------------

Table 8. Errors Noted at the Testing Laboratory During Accessioning for the Simple 2 Swab Home Collection Kit (Vaginal).

Success Rate
(b)(4)
Rejection Reasons:
(b)(4)

N/A Not applicable.

The results from the usability studies for both kits demonstrated that lay users are able to properly collect their own specimens and correctly perform the tasks associated with the packaging and shipping the samples. Further, results from the questionnaire support the conclusion that lay users demonstrated comprehension of the critical elements in the labeling,

{13}------------------------------------------------

including warnings, implications of the test results and the need to contact a healthcare provider as needed.

In addition, the second study for the urine kit showed that replacing generic transfer pipette with the graduated transfer pipette allows the users to transfer an appropriate amount of urine, which was a challenge with the previous version of the pipette.

2. FLEX STUDIES

To conduct analytical studies at the challenging concentrations (low positive) of CT and NG, the empirical LoD of the assay was established. In urine, the LoD was established at | @101 for NG and | | | | for CT. In negative vaginal swab specimens, the LoD was established at 10145 for NG and (000) for CT. All Flex Studies, Interference with Hand Contaminant, and Sample Shipping Stability studies were performed in reference to the empiric LoD.

A. Incorrect Volume of Urine Transferred to the Aptima Urine Transport Tube (Minimum Volume)

The manufacturer's instructions for the Aptima Combo 2 assay recommend a urine volume of 1000 to be transferred into the Aptima Urine Transport Tube for a final sample volume (urine + Aptima transport media) of (01/01/11 The package insert indicates that the final sample volume must be within the black fill lines indicated on the urine specimen transport tube. The study was performed to determine the effects of sample volumes below the maximum fill line, i.e. b of added urine (underfilled tubes) and above the maximum fill line (overfilled tubes). Negative male urine matrix was spiked with CT or GC organisms at the target concentration of LoD and the test samples were prepared by adding the spiked urine (for positive samples) and unspiked urine (for negative samples) into the | | | | of the transport medium at the volumes listed in Tables 9 and 10. 1014 positive and 1010 megative replicates of each sample were tested. The results for underfilled samples are presented in Table 9 below. Correct results were obtained for all negative samples tested and positive samples when at least | |0 | of urine was transferred into the Urine Transport Tube. For positive samples, urine volume below [014] failed to generate 100% positivity. The results for overfilled samples are presented in Table 10 below. Correct results were obtained for all negative and positive samples tested.

(b)(4) LoDCT#positives/#tested	CTAgreementwithexpectedresult	(b)(4) LoDGC#positives/#tested	GCAgreementwithexpectedresult	NegativeSamples	Negative SamplesAgreement withExpected Results(for CT and NG)
(b)(4)	100%	(b)(4)	100%	(b)(4)	100%
	100%		100%		100%
	100%		100%		100%
	100%		100%		100%
	80%		60%		100%
	80%		40%		100%
	0%		20%		100%

Table 9. Summary of Testing Underfilled Urine Transport Tubes.

{14}------------------------------------------------

Image /page/14/Picture/0 description: The image shows a gray rectangle with a red border. Inside the rectangle, there is the text '(b)(4)' in a small, light-colored font. The text is centered horizontally and vertically within the rectangle.

UrineVolume(mL)	(b)(4) LoDCT#positives/#tested	CTAgreementwithexpectedresult	(b)(4) LoDGC#positives/#tested	GCAgreementwithexpectedresult	NegativeSamples	Negative SamplesAgreement withExpected Results(for CT and NG)
(b)(4)	(b)(4)	100%	(b)(4)	100%	(b)(4)	100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%

Table 10. Summary of Testing Overfilled Urine Transport Tubes.

The study results showed that underfilling the Transport Tube with urine will generate accurate results if at least (0)(4) of the specified volume) of urine is transferred. The results also showed that the test is not sensitive to overfilling the Transport Tube. To mitigate the risk of user errors, the transfer pipette is marked to indicate the proper volume to be transferred and the instructions guide the user to ensure that the transferred urine volume is appropriate.

B. Incorrect Amount of Transport Media in the Aptima Urine Transport Tubes.

Aptima urine transport tubes are prepared by the manufacturer with a fixed amount of the transport media | | The transport media is responsible for cell lysis and subsequent stabilization of the resulting rRNA. Spilling or removing of the transport media from the sample tube could lead to a reduced transport media-to-urine volume ratio (intended ratio (0)4) which could lead to erroneous results. To determine if lower than the recommended volume of the transport media leads to erroneous results, the tubes were filled with several volumes, followed by addition of of urine samples; one set of test samples used low positive LoD) CT or GC urine samples, and the second set of samples used negative urine samples. [ 1 ] positive and [ 14 negative replicates were tested for each volume of the transport media. The results are presented in Table 11 below. Correct results were obtained for all negative and all positive samples tested.

Table 11. Summary of Testing Various Transport Media Volumes in the Urine Transport Tube.

TransportMediaVolume(mL)	UrineVolume(mL)	CTAgreementwithexpectedresult	(b)(4) LoDGC#positives/#tested	GCAgreementwith expectedresult	NegativeSamples	NegativeSamplesAgreement withExpected Results(for CT and NG)
(b)(4)	(b)(4)	100%	(b)(4)	100%	(b)(4)	100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		0%		100%

{15}------------------------------------------------

C. Delay of Urine Transfer to the Aptima Urine Transport Tubes.

The collection instructions direct the user to transfer the Urine Transport Tube after collection. The study was performed to determine the effect of delay of urine transfer from the collection cup to the Aptima Urine Transport Tubes. Negative male urine spiked with LoD CT or GC at time/day 0, was placed into a urine collection cup/box and stored on the bench top at room temperature ( 10%(4) | At each time point, as presented in the Table 12 below, a | b() | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Aptima Urine Specimen Transport Tube, and tested for the presence of GC/CT using the Aptima Combo 2 assay. [1019] positive and [0] negative replicates were tested at each time point. The results are presented in Table 12 below. Expected results were obtained for all negative samples. False negative results for CT were obtained when the urine was transferred to the Urine Transport Tube three weeks after placing in the collection cup/box. False negative results were obtained for GC when the transfer of urine to the Urine Transport Tube was delayed more than one day. Therefore, the IFU directs the user to transfer the urine right after the collection to mitigate the risk of erroneous results due to the delay in urine transfer to the Urine Transport Tube. Further, the directions specify that the sample should be sent to the lab on the same day as it is collected.

Time	CTAgreementwithexpectedresult	(b)(4) LoD GC#positives/#tested	GCAgreementwithexpectedresult	Negative Samples	Negative SamplesAgreement withExpected Result(for CT and NG)
(b)(4)	100%	(b)(4)	100%	(b)(4)	100%
	100%		100%		100%
	100%		100%		100%
	100%		0%		100%
	100%		0%		100%
	100%		0%		100%
	100%		0%		100%
	60%		0%		100%

Table 12. Summary of Testing the Delay of Urine Transfer to the Urine Transport Tube.

negative and equivocal result were obtained. a) (10014)

b) negative results were obtained.

c) negative results were obtained.

3. INTERFERING SUBSTANCES

A. Simple 2 Urine Home Collection Kit (Penile)

Studies were performed to evaluate the effect of inadvertent introduction of common hand contaminants to urine samples collected with Aptima urine transport tubes and tested using. the Aptima Combo 2 assay. Pooled male urine samples containing common hand contaminants (i.e., water, soap, hand sanitizer, lotion, and sunscreen) were spiked with GC or CT at PLOD to determine if accidental introduction of exogenous substances that may be introduced during specimen collection present a risk for false results. Multiple brands of each substance were tested at [ [0] positive and [0] negative replicates were tested for each

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

substance. The results are presented in Table 13 below. Expected results were obtained for negative and all CT positive samples. However, false negative results were obtained for GC in the presence of certain brands of hand soap and hand samitizer (Table 13). The limitations have been introduced in the labeling to caution the user about the interference. Additionally, the instructions direct the user to wash their hands in warm soapy water and dry thoroughly which serves to lower the risk of sample contamination.

Brand	CTAgreementwithexpectedresult	(b)(4) LoDGC#positives/#tested	GCAgreementwithexpectedresult	NegativeSamples	Negative SamplesAgreement withExpected Results(for CT and NG)
(b)(4)	100%	(b)(4)	100%	(b)(4)	100%
	100%		0%		100%
	100%		100%		100%
	100%		67%		100%
	100%		100%		100%
	100%		100%		100%
	100%		50%		100%
	100%		100%		100%
	100%		100%		100%
	100%		100%		100%
	100%		100%		100%
	100%		100%		100%
	100%		100%		100%

Table 13. Summary of Testing Interfering Substances in the Urine Transport Tube.

[b negative and [b] equivocal results were obtained. a)

b) [co) equivocal results were obtained.

c) negative and be equivocal result were obtained.

B. Simple 2 Swab Home Collection Kit (Vaginal)

Studies were performed to evaluate the effect of inadvertent introduction of common hand contaminants to vaginal swab samples collected with the Simple 2 Swab Home Collection Kit (Vaginal) and tested using the Aptima Combo 2 assay. Negative vaginal swab STM samples containing common hand contaminants (i.e., water, soap, hand sanitizer, lotion, and sunscreen) were spiked with GC or CT at (0) LoD to determine if inadvertent introduction of exogenous substances that may be introduced during specimen collection present a risk for false positive or false negative results. Multiple brands of each substance were tested at | [1] 1010 DI positive and prosive replicates were tested for each substance. The results are presented in Table 14 below. All samples generated expected results.

Table 14. Summary of Testing Interfering Substances in the Simple 2 Swab Home Collection Kit (Vaginal).

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

Brand	3x LoDCT#positives/#tested	CTAgreementwithexpectedresult	3x LoDGC#positives/#tested	GCAgreementwithexpectedresult	NegativeSamples	NegativeSamplesAgreementwithExpectedResults
(b)(4)	(b)(4)	100%	(b)(4)	100%	(b)(4)	100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%
		100%		100%		100%

4. SAMPLE SHIPPING STABILITY

A. Simple 2 Urine Home Collection Kit (Penile)

Shipping stability studies were performed to evaluate the stability of samples under extreme shipping conditions that samples may encounter when shipped via commercial carriers. Pooled negative male urine was spiked with live CT or GC at 01 (low positive) or 1084 LoD (moderate positive). Now positive. Pla moderate positive and Por negative samples were evaluated according to the Summer and Winter Shipping Temperature Cycles as indicated in Tables 15 and 17, respectively. The results from the study are presented in Tables 16 and 18. The expected results were generated for all samples tested under both Summer and Winter Shipping Temperature Cycles except DX() == Jsample tested at 1014 LoD under Winter Shipping Temperature Cycle. These data are acceptable sincel (014) (>95%) positive results were generated at [0] LoD. The data demonstrate that the urine sample integrity is maintained even when exposed to extremes of temperature during shipping.

Temperature	Cycle Period	Cycle Period (Hours)	Total Time (Hours)
(b)(4)

{18}------------------------------------------------

	(b)(4)
--	--------	--

Table 16. Summary Results for the Summer Shipping Temperature Cycle.

Concentration/Organism	CT# positive/#tested	GC# positive/#tested	CT/GC#negatives/#tested
(b)(4)

Table 17. Winter Shipping Temperature Cycle.

Temperature	Cycle Period	Cycle Period (Hours)	Total Time (Hours)
		(b)(4)

Table 18. Summary Results for the Winter Shipping Temperature Cycle.

Concentration/Organism	CT# positive/#tested	GC# positive/#tested	CT/GC#negatives/#tested
	(b)(4)

B. Simple 2 Swab Home Collection Kit (Vaginal)

The stability of the collected vaginal specimens under shipping conditions was evaluated by testing negative vaginal swabs in transport medium and positive vaginal swabs in transport medium (spiked with live CT or GC at (1) LoD (low positive) and 10/4) LoD (moderate positive)) after exposure to the Summer and Winter Shipping Temperature Cycles, as indicated in Tables 15 and 17, respectively. 10(4) |low positive, " | |high positive, and 10 negative samples were subjected to the extended Summer and Winter shipping profiles, as indicated in Tables 15 and 17 above. The results are presented in Tables 19 and 20 below. The expected results were generated for all samples tested under both Summer and Winter Shipping Temperature Cycles. The study results demonstrate that the vaginal swab sample integrity is maintained even when exposed to extremes of temperature during shipping.

Table 19. Summary Results for the Summer Shipping Temperature Cycle.

Concentration/Organism	CT# positive/#tested	GC# positive/#tested	CT/GC#negatives/#tested
(b)(4)

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

(D)(4)

Table 20. Summary Results for the Winter Shipping Temperature Cycle.

VII Proposed Labeling:

The labeling supports the decision to grant the De Novo request for this device.

VIII Identified Risks and Mitigations:

Identified Risks to Health	Mitigation Measures
Risk of false results	Certain labeling information including limitations,device descriptions, performance information, andexplanations of procedures.Use of certain specimen collection devices.Certain design verification and validation includingdocumentation of device descriptions, certain analyticalstudies and clinical studies, risk analysis strategies.
Failure to correctly interpret testresults	Certain labeling information including limitations,device descriptions, performance information, andexplanations of procedures.Certain design verification and validation includingdocumentation of device descriptions, certain analyticalstudies and clinical studies, risk analysis strategies.
Failure to correctly operate thedevice	Certain labeling information including limitations,device descriptions, performance information, andexplanations of procedures.Certain design verification and validation includingdocumentation of device descriptions, certain analyticalstudies and clinical studies, risk analysis strategies.

IX Benefit/Risk Assessment:

A Summary of the Assessment of Benefit:

The Simple 2 Test is the first over-the counter device for detection of chlamydia and gonorhea that allows for self-collection of specimens in the privacy of one's home (home collection). It is probable that the wide availability of this test without prescription will increase testing for STIs in patients who cannot or chose not to visit a healthcare provider, and who would not be tested otherwise. Because infections with Chlamydia trachomatis and Neisseria gonorrhoeae are often

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

asymptomatic. opening the access to testing at home will likely help curb the spread of these infections. Further, home collection of specimens for testing for sexually transmitted infections is desirable to patients, facilitating access to information about their sexual health without the need for a visit to a physician. Additionally, identification of these infections early in the course of disease will lead to more effective or more timely treatments and a reduction in the morbidity in sexually active individuals. The data submitted in this De Novo application demonstrates that lay users can effectively collect samples at home without compromising the performance of the test results provided by the Aptima Combo 2 assay.

B Summary of the Assessment of Risk:

The risks associated with the test are mainly the possibility of false positive and false negative test results. False negative test results can cause delays to effective treatment, progression to disseminated disease, and spread of infection to other persons throughout the community. According to the CDC guidelines, patients with known exposure to either gonorrhea or chlamydia (e.g., a sexual partner with positive diagnosis), should be empirically treated with antibiotics, regardless of the test result. Thus, a false negative result obtained by persons with known exposures to gonorrhea or chlamydia using this test may lead to delays or lost opportunities for treatment. A false negative result may also be obtained if the test is used within a short time after exposure. False positive results when using this test could lead to an incorrect diagnosis and unnecessary treatment for chlamvdia and gonorrhea. Additionally, false positive results may lead to risk of side effects from unnecessary treatments, as well as psychological distress. Further, the risks associated with the device are failure to correctly interpret test results and failure to correctly operate the device. These risks are mitigated by the special controls, mainly required analytical and clinical performance and required information in the labeling and educational information about CT and GC infections contained in the enclosed FAQ pamphlet.

C Summary of the Assessment of Benefit-Risk:

In conclusion, given the available information above, for the following indication statement:

The Simple 2 Test is intended for in vitro detection and identification of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) in home-collected specimens which are shipped to a CLIA compliant laboratory for testing using the Aptima Combo 2 Assay on the Panther System. This product is available over-the-counter (OTC) to consumers 18 years of age and older.

The Simple 2 Test Collection Kits may also be used to self-collect specimens in a clinic.

The testing is performed, as determined to be appropriate, based on the results of LetsGetChecked Suitability Questionnaire.

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

Testing is limited to the manufacturer, Priva Path laboratories (d.b.a. LetsGetChecked, Inc.).

The probable benefits outweigh the probable risks for the Simple 2 Test. The device provides benefits, and the risks can be mitigated by the use of general controls and the identified special controls.

X Conclusion:

The De Novo request is granted and the device is classified under the following and subject to the special controls identified in the letter granting the De Novo request:

Product Code: QYA Device Type: System for detection of nucleic acid from non-viral microorganism(s) causing sexually transmitted infections using home-collected specimens.

Class: II Regulation: 21 CFR 866.3385

Regulation Number and Section

N/A