Oragene Dx devices are intended for use in the non-invasive collection of saliva samples. Human 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.

Device Description

The Oragene-Dx family of products offers reliable collection, transportation and long-term room temperature storage of human DNA from saliva. Oragene Dx is a non-invasive alternative for collecting high quality and quantity DNA for use in molecular diagnostic applications. Oragene-Dx is a device family available in multiple device formats or models.

Oragene-Dx device formats OGD-510, OGD-600, OGD-610 and OGD-675, have the same collection principle and intended use as the FDA cleared Oragene-Dx formats (K110701). All Oragene-Dx formats consist of a collection tube, a DNA stabilizing liquid and optional sponges for assisted collection. In addition, Oragene·Dx device formats are made from the same physical and chemical materials. Oragene Dx formats differ in the amount of DNA stabilizing liquid in the tube and in the difference in the amount of saliva to be collected. The ratio of final sample to stabilizing liquid volume remains the same.

Saliva collection can take place at home, in a laboratory setting, physician's office, or in the field by untrained (naïve) or professional users. Saliva samples are collected into the device directly by spitting or by using the provided sponges. After saliva is collected, the stabilizing liquid is mixed with the sample. Upon contacting saliva cells, the stabilizing liquid lyses cellular and nuclear membranes to release and stabilize nucleic acids (DNA). Oragene-Dx 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 device pre-collection shelf life is 24 months at room temperature from the date of manufacture. Post collection, Oragene Dx samples are stable at room temperature for up to 12 months. Oragene Dx device performance and sample integrity are maintained during typical ambient transport and storage conditions.

AI/ML Overview

This document (K152556) describes a 510(k) premarket notification for the Oragene®Dx OGD-510, Oragene®Dx OGD-600, Oragene®Dx OGD-610, and Oragene®Dx OGD-675 devices. These devices are intended for the non-invasive collection of saliva samples, from which human DNA can be isolated, stabilized, and used in FDA-cleared molecular diagnostic applications. The submission references studies performed for the predicate device (Oragene®Dx OGD-500, K110701) to support the substantial equivalence of the new devices.

1. Table of acceptance criteria and reported device performance:

Since the document bases its claims on substantial equivalence to a predicate device (K110701) and applicable studies mentioned in that predicate, specific numerical acceptance criteria for the new devices are not explicitly stated in a tabular format within this document. Instead, the document states that the performance of the new devices is "the same as predicate" or that "both OGD-510 and OGD-500 samples met acceptance criteria for DNA concentration, total DNA yield, A260/A280 ratio and performance on the eSensor Warfarin Sensitivity Saliva Test."

The key performance characteristics and their reported outcomes, primarily referencing the predicate K110701, are summarized below:

Performance Characteristic	Acceptance Criteria (Implied / Referenced from K110701)	Reported Device Performance (New Devices OGD-510, OGD-600, OGD-610, OGD-675)
Reproducibility/Precision	Meeting study acceptance criteria (as per K110701)	Demonstrated (referencing Section 18.4 of K110701). Overall, all samples tested met study acceptance criteria.
Pre-collection Shelf-Life	24 months at room temperature	Supported by studies in K110701 (same physical/chemical components).
	12 months at -20±5°C and 6±4°C	Supported by studies in K110701 (same physical/chemical components).
Post-collection Sample Stability	12 months at room temperature, -20±5°C or 6±4°C	Supported by studies in K110701 (same physical/chemical components).
	3 months at 50±5°C	Supported by studies in K110701 (same physical/chemical components).
Sample Volume Tolerance	No impact on performance from underfilling by 25-50% or overfilling by 50% of target volume (as per K110701)	Demonstrated (referencing Section 18.2 of K110701). Downstream performance was not affected by over or under spitting.
Interfering Substances	No impact on performance from endogenous/exogenous substances, 100% agreement between eSensor® Warfarin Sensitivity Test genotyping and bidirectional sequencing (as per K110701)	Demonstrated (referencing Section 18.6 of K110701), with the caveat of donor collection instructions (no eating, drinking, smoking, or chewing gum 30 min prior to collection).
Analytical Performance (DNA Concentration, Yield, A260/A280, Genotyping Agreement with eSensor Warfarin Sensitivity Saliva Test)	Meeting acceptance criteria for DNA concentration, total DNA yield, A260/A280 ratio, and performance on the eSensor Warfarin Sensitivity Saliva Test.	For OGD-510 (and applicable to OGD-610): Both OGD-510 and OGD-500 samples met acceptance criteria for these parameters. No significant difference in any performance parameters (except total sample DNA yield).

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

The document refers to studies in the predicate K110701 for most performance characteristics. For the new comparison study performed for OGD-510 vs. OGD-500, the sample size is not explicitly mentioned. The data provenance is implied to be from Canada, as the submitter, DNA Genotek Inc., is located in Ottawa, Ontario, Canada. The studies are retrospective references to the predicate device or a new comparison study.

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

This information is not explicitly provided in the document. The ground truth for comparative performance (genotyping) would likely be established by the "bidirectional sequencing" method, but details on the experts involved in interpreting this or verifying the ground truth for other studies (e.g., stability) are not given.

4. Adjudication method for the test set:

Not applicable or provided for this type of device and performance testing. The "ground truth" for genotyping involved comparison to bidirectional sequencing.

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

Not applicable. This device is a sample collection and stabilization device, not an AI-assisted diagnostic tool requiring human reader interpretation.

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

Not applicable. This is a physical device for sample collection, not an algorithm. The "performance" refers to the ability to collect and preserve DNA for downstream molecular diagnostic applications. The comparison studies against the eSensor® Warfarin Sensitivity Saliva Test (K110786) are standalone evaluations of the collected sample's compatibility with a molecular diagnostic test.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

For the analytical performance (genotyping agreement), the ground truth was established by bidirectional sequencing. For other performance characteristics like stability and reproducibility, the ground truth would be based on established laboratory methods and controls to demonstrate the integrity and functionality of the DNA.

8. The sample size for the training set:

Not applicable. This device is a physical sample collection device, not an algorithm that requires a training set.

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

Not applicable. No training set is involved for this type of device.

Summary

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

May 26, 2016

DNA GENOTEK, INC. DAN FULLERTON 2 BEAVERBROOK ROAD OTTAWA, ONTARIO K2K 1L1 CANADA

Re: K152556

Trade/Device Name: Oragene®Dx OGD-510. Oragene®Dx OGD-600. Oragene®Dx OGD-610, Oragene®Dx OGD-675 Regulation Number: 21 CFR §862.1675 Regulation Name: Blood specimen collection device Regulatory Class: II Product Code: OYJ Dated: April 19, 2016 Received: April 21, 2016

Dear Mr. 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 (OS) 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/ResourcesforYou/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,

Courtney H. Lias -S

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

510(k) Number (if known) K152556

Device Name Oragene Dx: OGD-510; OGD-600; OGD-610; OGD-675

Indications for Use (Describe)

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)

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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:	18 April 2016
Submitter:	DNA Genotek Inc.3000 – 500 Palladium Drive, Ottawa, Ontario K2V 1C2 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-510, OGD-600, OGD-610, OGD-675
Common names	Kit for collection of human DNA, Saliva kit, Sample collection kit
Proposed DeviceRegulatory Classification	Regulation: 21CFR 862.1675 Blood specimen collection devicePanel: Chemistry (75)Classification: Class IIProduct Code: OYJ DNA Specimen Collection, Saliva
Predicate DeviceRegulatory Classification	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

Oragene Dx devices are intended for use in the non-invasive collection of saliva samples. Human 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.

Indications for use

See Intended Use, above.

Special conditions for use statement

For prescription use.

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DEVICE DESCRIPTION

SUBSTANTIAL EQUIVALENCE INFORMATION

Principle,Materials andTechnology	Predicate devicesOragene·Dx: OGD-500, OGD-575,OYD-500, OXD-500 (K110701)	Subject devicesOragene·Dx: OGD-510, OGD-600, OGD-610, OGD-675	Similar	Different
Intended Use	Oragene·Dx is intended for use inthe non-invasive collection ofsaliva samples. DNA from thesaliva sample is isolated,stabilized, and suitable for use inFDA cleared molecular diagnosticapplications. Saliva may becollected by spitting directly intothe Oragene·Dx container or maybe transferred into theOragene·Dx container using asponge. Saliva samples collectedusing Oragene·Dx are stabilized	Same as predicate	X
Principle,Materials andTechnology	Predicate devices	Subject devices	Similar	Different
	Oragene-Dx: OGD-500, OGD-575,OYD-500, OXD-500 (K110701)	Oragene-Dx: OGD-510, OGD-600, OGD-610, OGD-675
	and can be transported and/orstored long term at ambientconditions.
Specialconditions foruse	Prescription	Same as predicate	X
Analyte	Human DNA	Same as predicate	X
Devicephysicaldesign	Consists of a collection tube, aDNA stabilizing liquid and optionalsponges for assisted collection.	Same as predicate	X
Samplecollection	Non-invasive collection ofbiological samples delivered into anon-sterile plastic collection tube	Same as predicate	X
Instructionsfor use	Multiple languages	English only (except OGD-510)		X
Formats	Multiple	Same as predicate	X
Tube material	Plastic	Same as predicate	X
Samplesource	Human saliva	Same as predicate	X
Additive	Nucleic acid stabilization solution	Same as predicate	X
Transport andStability	Pre-collection Oragene-Dx kits canbe transported at temperaturesranging from -20°C to 50°CPost-collection Oragene-Dxsamples can be transported attemperatures ranging from -20°Cto 50°CPre-collection Oragene-Dx kits canbe stored at room temperature forup to 24 monthsPost-collection Oragene-Dxsamples can be stored at roomtemperature for up to 12 months(OGD-500, OGD-575, OYD-500)and 3 months for OXD-525	Same as predicate	X
Principle,Materials andTechnology	Predicate devicesOragene-Dx: OGD-500, OGD-575, OYD-500, OXD-500 (K110701)	Subject devicesOragene-Dx: OGD-510, OGD-600, OGD-610, OGD-675	Similar	Different
Performance	Performance has beenestablished with the eSensor®Warfarin Sensitivity Saliva Test	Same as predicate	X

The following table outlines the similarities and differences between predicate and subject devices.

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DNA genotek

==================================================================================================================================================================

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The similarities in intended use, materials, technological characteristics show that Oragene Dx devices OGD-510, OGD-600, OGD-610, OGD-675 are substantially equivalent to Oragene Dx devices (K110701). The difference tabulated above does not affect the safety and performance of the device. Oragene-Dx device performance has been validated using GenMark Diagnostics' FDA cleared eSensor Warfarin Sensitivity Saliva Test (K110786).

PERFORMANCE CHARACTERISTICS

REPRODUCIBILITY/PRECISION

The reproducibility of the Oragene-Dx devices has been demonstrated; see section 18.4 of K110701. Two reproducibility studies were performed and evaluated device reproducibility using prepared sample panels and the reproducibility of sample collection, processing and testing procedures. Overall, all samples tested met study acceptance criteria.

SHELF LIFE AND STABILITY

Pre-collection shelf-life

Shelf-life stability testing of the Oragene Dx device has been demonstrated; see Section 18.3 of K110701. Oragene-Dx formats OGD-510, OGD-600, OGD-610 and OGD-675 are comprised of the same physical and chemical components as the FDA cleared Oragene·Dx formats; therefore, studies in K110701 support the following shelf-life performance claims:

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 devices has been demonstrated; see Section 18.3 of K110701. The Oragene Dx formats OGD-510, OGD-600, OGD-610 and OGD-675 are comprised of the same physical and chemical components as the FDA cleared Oragene Dx formats; therefore, studies in K110701 support the following sample stability performance claims:

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

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DETECTION LIMIT

Sample Volume Tolerance

The effect of overfilling or underfilling the Oragene Dx device has been demonstrated; see section 18.2 of K110701. Oragene-Dx formats OGD-510, OGD-600, OGD-675 are comprised of the same physical and chemical components as the FDA cleared Oragene Dx formats. 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 vield was dependent on collected volume, but downstream performance was not affected by over or under spitting.

INTERFERING SUBSTANCES

The effect of endogenous and exogenous interfering substances has been demonstrated; see Section 18.6 of K110701. The Oragene-Dx formats OGD-510, OGD-610 and OGD-675 are comprised of the same physical and chemical components as the FDA cleared Oragene-Dx formats. In summary, in accordance with the donor collection instructions for use that specify no eating, drinking, smoking , or chewing gum 30 minutes prior to saliva collection this study demonstrates that there was no impact on performance from the introduction of either endogenous substances or exogenous substances into Oragene Dx saliva samples tested had 100% agreement between eSensor® Warfarin Sensitivity Test genotyping and bidirectional sequencing.

COMPARISON STUDIES

Matrix comparison was evaluated in K110701; see Section 18.5. Method comparison studies were previously completed with the eSensor Warfarin Sensitivity Saliva Test; see K110786. The Oragene-Dx formats OGD-510, OGD-600, OGD-610 and OGD-675 are comprised of the same physical and chemical components as the FDA cleared Oragene-Dx formats, therefore these comparison studies are applicable.

A new study was conducted to evaluate the analytical performance of OGD-510 (DNA concentration, yield, A260/A280 ratio and agreement between genotyping on the eSensor Warfarin Sensitivity Saliva Test and bidirectional sequencing), and performance was compared to that of OGD-500. This study is also applicable to OGD-610 as it is an equivalent format to OGD-510. Overall, both OGD-510 and OGD-500 samples met acceptance criteria for DNA concentration, total DNA yield, A260/A280 ratio and performance on the eSensor Warfarin Sensitivity Saliva Test. There was no significant difference in any performance parameters (with the expected exception of total sample DNA yield) between the two formats.

CONCLUSION

The submitted information in this premarket notification is complete and supports the safety and effectiveness of the Oragene-Dx OGD-510, OGD-600, OGD-610 and OGD-675 formats and substantial equivalence to the predicate devices (Oragene-Dx K110701). As established in K110701 and in this submission, the difference in the formats of the subject Oragene Dx devices conferred no differences in the performance of the stabilized and/or purified DNA.

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.