Oragene®●Dx OGD-500.001 is intended for use in the non-invasive collection of saliva samples. DNA from the saliva sample is isolated, stabilized, and suitable for over-the-counter use with FDA cleared, approved, or legally marketed exempt DNA carrier screening genotyping tests. Saliva samples collected using Oragene®Dx OGD-500.001 are stabilized and can be transported and/or stored long term at ambient conditions.

Device Description

Oragene Dx family of collection devices offers reliable collection, transportation and longterm ambient temperature storage of human DNA from saliva. Oragene Dx OGD-500.001 is a noninvasive alternative for collecting high quality and quantity DNA and is suitable for use in over-thecounter molecular genotyping applications. Oragene-Dx OGD-500.001 consists of a collection tube with a funnel lid attached (containing a stabilizing liquid). Saliva is delivered directly by spitting into the collection tube. Saliva collection can take place at home, in a laboratory setting, physician's office, or in the field. Untrained (naïve) or professional users can carry out saliva collection. After saliva is collected, the stabilizing liquid is mixed with the sample. A small cap is provided to close the tube for transport and storage (funnel with lid is removed and discarded). Upon contacting saliva cells, the stabilizing liquid lyses cellular and nuclear membranes to release and stabilize nucleic acids (DNA). Samples can be immediately processed, transported or stored for future use. Samples can be shipped at ambient temperature to the laboratory for processing. Oragene-Dx samples are stable at room temperature for up to 12 months. Device and sample integrity are preserved during typical ambient transport and storage conditions.

AI/ML Overview

The document describes the Oragene® Dx OGD-500.001 device, a saliva collection kit, and its performance characteristics for substantial equivalence to a predicate device (Oragene® Dx OGD-500).

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly listed in a single table with numerical targets, but rather are inferred from the performance characteristics studies conducted and the claims made. The summary demonstrates that the device performs equivalently or acceptably based on these studies.

Acceptance Criteria (Inferred)	Reported Device Performance (Oragene® Dx OGD-500.001)
Reproducibility/Precision: Reliable genotyping across multiple operators, days, and reagent lots.	Demonstrated reproducibility when used with the 23andMe PGS Carrier Screening Test (details in co-submission DEN140044).
Pre-collection Shelf-life: Stability for extended periods.	24 months at room temperature; 12 months at -20°C ± 5°C and 6°C ± 4°C. (Supported by K110701, as device components are identical to predicate).
Post-collection Sample Stability: DNA yield, concentration, A260/A280 ratio, and microbial content maintained.	12 months at room temperature, -20°C ± 5°C or 6°C ± 4°C; 3 months at 50°C ± 5°C. (Supported by K110701, as device components are identical to predicate).
Sample Volume Tolerance: Functionality maintained with varying saliva volumes.	Underfilling by 25% or 50%, or overfilling by 50% did not impact performance. Mean total sample volume in consumer study: 4.25 ± 0.56 mL (equivalent to 2.25 mL saliva). 97.7% of samples were within acceptable range (2.58 to 5.64 mL total sample).
Limit of Detection (DNA Concentration): Sufficient DNA for downstream testing.	98.3% of samples in the consumer study contained the minimum amount of DNA required for testing. Re-extraction performed if initial concentration is low.
Interfering Substances (Endogenous): No impact on genotyping from natural saliva components.	100% concordant genotype calls for all samples and all endogenous substance conditions tested (salivary α-amylase, hemoglobin, immunoglobulin A, combination).
Interfering Substances (Exogenous): No impact on genotyping from common oral activities/substances.	100% concordant genotype calls for all samples collected immediately after and 30 minutes after consuming exogenous substances (food, drinking, chewing gum, mouthwash) or smoking.
Consumer Usability/Comprehension (OTC Setting): Ability of naïve users to correctly collect samples and obtain sufficient DNA.	98.3% of samples from 302 consumer study participants contained the minimum amount of DNA required for testing. User comprehension of test instructions was assessed.
Labeling Readability: Instructions are easily understood by general public.	Flesch-Kincaid reading grade level of 7.1 obtained for collection device labeling.

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

Reproducibility/Precision: Specific sample size not provided in this document, but referred to co-submission DEN140044 for the 23andMe PGS Carrier Screening Test.
Interfering Substances (Endogenous): 10 individuals for saliva samples.
Interfering Substances (Exogenous): 5 individuals at 3 time points (baseline, 0 min, 30 min) for each substance; smoking tested in a separate study (sample size not specified for smoking or overall study).
Consumer User Study: 302 individuals completed the survey and provided a saliva sample. The majority (96.3%) were naïve users.

Data Provenance (Retrospective or Prospective / Country of Origin):

The studies regarding pre-collection shelf-life and post-collection sample stability and sample volume tolerance refer back to information established in the predicate device's 510(k) (K110701). This suggests a mix of potentially existing data from the predicate and current validation for the proposed device where applicable.
The reproducibility, interfering substances, and consumer user study were performed in conjunction with the 23andMe PGS Carrier Screening Test (co-submission DEN140044). The study design (e.g., collecting samples before/after substances) indicates these were prospective studies. The country of origin for the data is not explicitly stated, but 23andMe is a US-based company, which might imply data from the US market. The submitter is DNA Genotek Inc., located in Canada.

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

This type of device (a sample collection kit) does not typically involve expert review for "ground truth" in the same way an imaging or diagnostic algorithm would. The ground truth in these studies is the actual measured performance of the device in yielding DNA, maintaining DNA quality, and ensuring accurate genotyping by a downstream FDA-cleared test. The "experts" would be the laboratory personnel and analytical methods used for DNA extraction, quantification, and genotyping, verifying aspects like DNA yield, purity, and concordance with known genetic markers. No specific number or qualifications of "experts" are provided as a distinct category for establishing ground truth, as the ground truth is based on laboratory measurements and analytical results.

4. Adjudication Method for the Test Set

Not applicable for a sample collection device. Adjudication methods like "2+1" (two readers agree, third resolves) are typically used in clinical imaging or diagnostic studies where subjective interpretation is involved. Here, the outcomes are objective laboratory measurements (DNA concentration, genotype concordance).

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

No. An MRMC comparative effectiveness study is not relevant for this device. This type of study compares the performance of multiple human readers on multiple cases, often with and without AI assistance, to measure the effect of AI on human reader performance. The Oragene Dx OGD-500.001 is a sample collection device, not an AI diagnostic tool that assists human readers.

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

Yes, in a sense, the performance of the device itself (collecting and stabilizing DNA) is assessed in a standalone manner. The studies evaluate the device's ability to provide suitable DNA for downstream testing, independently of human interpretation of that DNA. The "algorithm" here is the collection and stabilization process, and its output (stabilized DNA) is directly measured and assessed against objective criteria (DNA yield, purity, genotyping concordance).

7. The Type of Ground Truth Used

The ground truth used in these studies is primarily objective laboratory measurements and genotyping concordance.

DNA Yield and Purity: Measured directly using laboratory techniques (e.g., spectrophotometry for A260/A280 ratio, fluorometry for DNA concentration).
Genotyping Concordance: Comparison of genotypes obtained from samples collected with the device against reference genotypes (e.g., from unadulterated samples for interference studies, or known genetic profiles if applicable), using an FDA-cleared genotyping test (23andMe PGS Carrier Screening Test). This is a form of outcome data as it assesses the device's ability to enable correct biological outcomes (accurate genotyping).
Microbial Content: Laboratory assay for the presence of microbes.

8. The Sample Size for the Training Set

No training set is mentioned or applicable for this type of device. Training sets are typically used for machine learning or AI models, which is not the function of this saliva collection device. The device itself is a physical product, and its performance is characterized through validation studies, not by training an algorithm.

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

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

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

February 19, 2015

DNA GENOTEK, INC. DAN FULLERTON VICE PRESIDENT OPERATIONS, QUALITY AND REGULATORY 2 BEAVERBROOK ROAD OTTAWA K2K 1L1 CANADA

Re: K141410

Trade/Device Name: Oragene® Dx OGD-500.001 Regulation Number: 21 CFR 862.1675 Regulation Name: Blood specimen collection device Regulatory Class: II Product Code: OYJ Dated: January 20, 2015 Received: January 21, 2015

Dear Mr. Dan Fullerton:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal 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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Katherine Serrano -A

For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) K141410

Device Name Oragene.Dx OGD-500.001

Indications for Use (Describe)

OragenerDx OGD-500.001 is intended for use in the non-invasive collection of saliva samples. DNA from the saliva sample is isolated, stabilized, and suitable for over-the-counter use with FDA cleared, approved, or legally marketed. exempt DNA carrier screening genotyping tests. Saliva samples collected using Oragene®Dx OGD-500.001 are stabilized and can be transported and/or stored long term at ambient conditions.

Type of Use (Select one or both, as applicable)
	Prescription Use (Part 21 CFR 801 Subpart D)
	Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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510(k) Summary

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1900 and CFR 807.92.

Date:	16 January 2015
Submitter:	DNA Genotek Inc.2 Beaverbrook Road, Ottawa,Ontario K2K 1L1 Canada
Contact:	Dan FullertonVice President Operations, Quality & Regulatory AffairsTel: (613) 723-5757 Ext. 213, Fax: (613) 368-4628Email: dan.fullerton@dnagenotek.com
Device Proprietary Name	Oragene®•DxFormat: OGD-500.001
Common names	Kit for collection of human DNA, Saliva kit, Sample collection kit for use inover-the-counter genetic testing
Proposed DeviceRegulatory Classification	Regulation: 21CFR 862.1675 Blood specimen collection devicePanel: Chemistry (75)Classification: Class IIProduct Code: OYJ DNA Specimen Collection, Saliva
Predicate Device	Oragene®•Dx OGD-500 (K110701)Regulation: 21CFR 862.1675 Blood specimen collection devicePanel: Chemistry (75)Classification: Class IIProduct Code: OYJ DNA Specimen Collection, Saliva

INTENDED USE

Intended use

Indications for use

See Intended Use, above.

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Special conditions for use statement

Intended for adults of reproductive age.

DEVICE DESCRIPTION

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SUBSTANTIAL EQUIVALENCE INFORMATION

The following table outlines the similarities and differences between Oragene-Dx OGD-500 (predicate) and Oragene·Dx OGD-500.001 (proposed device).

Principle, Materials and Technology	Oragene-Dx OGD-500(predicate - K110701)	Oragene-Dx OGD-500.001(proposed device)	Similar	Different
Intended Use	Oragene-Dx is intended for use in the non-invasive collection of saliva samples. DNA from the saliva sample is isolated, stabilized, and suitable for use in FDA cleared molecular diagnostic applications. Saliva may be collected by spitting directly into the Oragene-Dx container or may be transferred into the Oragene-Dx container using a sponge. Saliva samples collected using Oragene-Dx are stabilized and can be transported and/or stored long term at ambient conditions.	Oragene®•Dx OGD-500.001 is intended for use in the non-invasive collection of saliva samples. DNA from the saliva sample is isolated, stabilized, and suitable for over-the-counter use with FDA cleared, approved, or legally marketed exempt DNA carrier screening genotyping tests. Saliva samples collected using Oragene•Dx OGD-500.001 are stabilized and can be transported and/or stored long term at ambient conditions.	X
Special conditions for use	Prescription	Over the counter		X
Analyte	DNA	DNA	X
Sample collection	Non-invasive collection of biological samples delivered into a non-sterile plastic collection tube	Non-invasive collection of biological samples delivered into a non-sterile plastic collection tube	X
Tube material	Plastic	Plastic	X
Sample source	Human saliva	Human saliva	X
Additive	Nucleic acid stabilization solution	Nucleic acid stabilization solution	X

	Table 1. Comparison between Predicate and Proposed device

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Principle,Materials andTechnology	Oragene·Dx OGD-500(predicate – K110701)	Oragene·Dx OGD-500.001(proposed device)	Similar	Different
Transport andStability	Pre-collection Oragene·Dx kitscan be transported attemperatures ranging from-20°C to 50°C	Pre-collection Oragene·Dx kitscan be transported attemperatures ranging from-20°C to 50°C	X
	Post-collection Oragene·Dxsamples can be transported attemperatures ranging from-20°C to 50°C	Post-collection Oragene·Dxsamples can be transported attemperatures ranging from-20°C to 50°C
	Pre-collection Oragene·Dx kitscan be stored at roomtemperature for up to 24months	Pre-collection Oragene·Dx kitscan be stored at roomtemperature for up to 24months
	Post-collection Oragene·Dxsamples can be stored at roomtemperature for up to 12months (OGD-500, OGD-575,OYD-500) and 3 months forOXD-525	Post-collection Oragene·Dxsamples can be stored at roomtemperature for up to 12months
Performance	Performance has beenestablished with the eSensor®Warfarin Sensitivity Saliva Test	Performance has beenestablished with the 23andMePersonal Genome Service (PGS)Carrier Screening Test		X

The similarities in intended use, materials, and technological characteristics show that Oragene-Dx OGD-500.001 (K141410) is substantially equivalent to Oragene·Dx OGD-500 (K110701). The differences tabulated above do not affect the safety and performance of Oragene·Dx OGD-500.001. Oragene·Dx OGD-500 performance has been validated using GenMark Diagnostics' FDA cleared eSensor Warfarin Sensitivity Saliva Test. Oragene-Dx OGD-500.001 performance has been validated with the 23andMe PGS Carrier Screening Test.

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PERFORMANCE CHARACTERISTICS

Reproducibility/Precision

Reproducibility of the Oragene-Dx OGD-500.001 collection device was validated when used with the 23andMe PGS Carrier Screening Test. Reproducibility was demonstrated across multiple operators, days and reagent lots (see PGS Carrier Screening Test co-submission DEN140044).

Stability

Pre-collection shelf-life

Shelf-life stability testing of the Oragene·Dx device has been demonstrated (see K110701).

The Oragene-Dx OGD-500.001 format is comprised of the same physical and chemical components as the FDA cleared Oragene Dx OGD-500 format; therefore, studies in K110701 support the following shelflife performance claims for OGD-500.001:

24 months at room temperature
. 12 months at -20±5°C and 6±4°C

Post-collection sample stability

Post-collection sample stability of the Oragene-Dx device (OGD-500) has been demonstrated in studies evaluating DNA vield, DNA concentration, A260/A280 ratio and microbial content (see K110701). The Oragene Dx OGD-500.001 format is comprised of the same physical and chemical components as the FDA cleared Oragene Dx OGD-500 format; therefore, studies in K110701 support the following sample stability performance claims for OGD-500.001:

12 months at room temperature, -20±5°C or 6±4°C ●
3 months at 50±5°C ●

Sample Volume Tolerance and Limit of Detection

The effect of overfilling or underfilling the Oragene·Dx device has been evaluated (see K110701). Oragene Dx OGD-500.001 format is comprised of the same physical and chemical components as the FDA cleared Oragene Dx OGD-500 format. As demonstrated, underfilling the Oragene Dx device (OGD-500) by 25% or 50% of target volume, or overfilling by 50% of target volume did not impact performance. Collected samples ranged from as low as 0.58mL saliva to as much as 3.64 mL saliva. As expected the DNA yield was dependent on collected volume, but downstream performance was not affected by over or under spitting.

These results were further validated in a Consumer User Study where sample volume was measured in samples submitted from naive users in the over-the-counter setting of the 23andMe PGS Carrier Screening Test. Collected samples had a mean total sample volume (saliva + stabilizing solution) of 4.25 ± 0.56 mL (equivalent to mean of 2.25 mL saliva). 97.7% of samples contained the acceptable range of 2.58 to 5.64 mL total sample.

The 23andMe PGS Carrier Screening Test also requires a minimum DNA concentration. To ensure this concentration is met, the DNA concentration of every sample submitted for testing is measured. If the

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extracted DNA concentration is below the minimum DNA concentration is attempted. If re-extraction is unsuccessful, the customer is contacted to submit a new saliva sample. 98.3% of samples in the study contained the minimum amount of DNA required for testing.

Interfering Substances

Endogenous Substances

The effect of potentially interfering endogenous substances on performance of saliva samples collected with the Oragene Dx OGD-500.001 device on the 23andMe PGS Carrier Screening Test was evaluated (see PGS co-submission DEN140044). Saliva samples were collected from 10 individuals. These saliva samples were sent to the contracted laboratory for DNA extraction and genotyping. At the contracted laboratory, the following substances were spiked separately into an aliquot of each saliva sample before DNA extraction: salivary a-amylase, hemoglobin, immunoglobulin A, and a combination of a-amylase, immunoglobulin, and human serum albumin (total protein). An additional saliva sample aliquot was not spiked and served as the control. For each individual, genotypes of the samples containing each endogenous substance were compared with the genotype of the original unadulterated sample (considered control) to determine percent concordance.

This endogenous interference study yielded 100% concordant genotype calls for all samples and all endogenous substance conditions. The results of this study indicate that the presence of endogenous substances in human saliva does not affect the ability of the 23andMe PGS Carrier Screening Test to correctly assign genotypes to saliva samples.

Exogenous Substances

The effect of potentially interfering exogenous substances on the performance of saliva samples collected with the Oragene Dx OGD-500.001 device on the PGS Carrier Screening Test has been evaluated (see PGS co-submission DEN140044). Saliva samples were collected from 5 individuals at 3 time points – before consuming an exogenous substance (baseline), immediately (0 minutes) after, and 30 minutes after – and sent to the contracted laboratory for DNA extraction and genotyping. For each individual, genotypes of the 0 and 30 minute samples were compared with genotypes of the baseline sample (considered control) to determine percent concordance. The following exogenous interference conditions were tested separately: eating food containing beef, eating food other than beef, drinking, chewing gum, and using mouthwash. Smoking was tested following the same methodology in a separate study.

This interference study yielded 100% concordant genotype calls for all samples collected immediately after and 30 minutes after consuming an exogenous substance or smoking. These data are consistent with the package insert instructions, which require the consumer to take nothing by mouth for 30 minutes prior to saliva collection.

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Consumer User Study

Performance of the Oragene Dx OGD-500.001 device when used in the over-the-counter setting of the 23andMe PGS Carrier Screening Test was evaluated. New 23andMe customers who registered their kit within consecutive 24-hour periods were invited to participate in the study survey via email. Samples from customers who completed the survey were shipped to the testing laboratory. Upon receipt at the testing laboratory, each study sample was assessed for compliance to collection instructions and sample volume, DNA concentration, and DNA purity (A260/A280 ratio) was assessed. User comprehension of test instructions, including comprehension of sample collections was also assessed.

A total of 302 individuals completed the user comprehension survey and provided a saliva sample for analysis. The majority of participants (96.3%) were naïve to the device and saliva collection process. Of the 302 samples evaluated, 98.3% contained the minimum amount of DNA required for testing, demonstrating that customers were able to follow sample collection instructions to obtain adequate sample for testing. See PGS co-submission DEN140044 for additional user study information.

A Flesch-Kincaid reading analysis was performed on the collection device labeling and a reading grade level of 7.1 was obtained.

CONCLUSION

The submitted information in this premarket notification is complete and supports the safety and effectiveness of the Oragene·Dx OGD-500.001 for over-the-counter use.

Regulation Number and Section

§ 862.1675 Blood specimen collection device.

(a)
Identification. A blood specimen collection device is a device intended for medical purposes to collect and to handle blood specimens and to separate serum from nonserum (cellular) components prior to further testing. This generic type device may include blood collection tubes, vials, systems, serum separators, blood collection trays, or vacuum sample tubes.(b)
Classification. Class II.