ORAcollect.Dx

• K Number: K152464
• Device Name: ORAcollect.Dx
• Manufacturer: DNA GENOTEK INC.
• Date Cleared: 2016-05-26 ( 269 days)
• Product Code: OYJ
• Regulation Number: 862.1675

Intended Use

ORAcollect Dx is 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 sample sultured using ORAcollect+Dx are stabilized and can be transported and/or stored long term at anbient can adions.

Device Description

The ORAcollect-Dx family of collection devices offers reliable collection, transportation and long-term ambient temperature storage of human DNA from saliva. ORAcollect-Dx is a non-invasive alternative for collecting high quality and quantity human DNA and is suitable for use in molecular diagnostic applications. ORAcollect-Dx consists of a collection tube containing a stabilizing liquid and a double ended cap with an integrated sponge used to collect a saliva sample. After receiving instruction from a professional, saliva collection can take place in a laboratory setting, physician's office, at home, or in the field. Untrained (naïve) or professional users can carry out saliva collection. Using the provided instructions for use, the integrated sponge on the device to collect a saliva sample from the mouth. After saliva is collected, the cap is removed from the tube, inverted to place the sponge into the collection tube with the stabilizing liquid, and re-capped with the sponge remaining inside the tube. 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. ORAcollect-Dx device pre-collection shelf life is 24 months at room temperature (15°C to 25°C) from the date of manufacture. Post collection, ORAcollect·Dx samples are stable at room temperature for up to 60 days. ORAcollect · Dx device and sample integrity are preserved during typical ambient transport and storage conditions.

Predicate Devices

Oragene•Dx OGD-500 (K110701)

Reference Devices

K152612

AI/ML (Artificial Intelligence / Machine Learning)

No
The device is a saliva collection kit and the summary focuses on the physical components, collection process, and sample stability. There is no mention of any software, algorithms, or data processing that would involve AI/ML.

Therapeutic

No
This device is for the collection, transportation, and long-term storage of human DNA samples from saliva for use in FDA cleared molecular diagnostic applications. It does not provide any therapeutic benefit or treatment to a patient.

Diagnostic

No

This device is a sample collection and stabilization device for DNA, not a diagnostic device itself. Its output (stabilized DNA from saliva) is intended for use in pre-existing FDA-cleared molecular diagnostic applications, as stated in the "Intended Use / Indications for Use" section. It collects and prepares the sample, but does not perform the diagnostic analysis or provide a diagnostic result.

SaMD (Software as a Medical Device)

No

The device description clearly states it consists of a collection tube, stabilizing liquid, and a cap with an integrated sponge, which are all physical hardware components.

IVD (In Vitro Diagnostic)

Based on the provided information, the ORAcollect Dx device is not an IVD itself.

Here's why:

• Intended Use: The intended use states that ORAcollect Dx is for the collection of saliva samples and the stabilization of human DNA from those samples. It explicitly states that the DNA is "suitable for use in FDA cleared molecular diagnostic applications." This indicates that the device is a component or a pre-analytical tool for IVD tests, but not the diagnostic test itself.
• Device Description: The description reinforces that it's a collection device for obtaining DNA from saliva. It describes the process of collecting and stabilizing the sample.
• Performance Studies: The performance studies evaluate the device's ability to collect and preserve DNA that is suitable for use in an IVD test (specifically, the eSensor Warfarin Sensitivity Saliva Test, which is listed as a Reference Device). The studies focus on DNA quality (concentration, yield, A260/A280 ratio) and the agreement of genotyping results obtained using DNA collected with the device when tested on the reference IVD. They are not evaluating the diagnostic performance of the ORAcollect Dx device itself.
• Predicate and Reference Devices: The predicate devices are other saliva collection devices. The reference device is an FDA-cleared IVD test that uses saliva samples. This further supports that ORAcollect Dx is a collection device used with an IVD, rather than being an IVD itself.

In summary, ORAcollect Dx is a sample collection and stabilization device intended for use with FDA-cleared molecular diagnostic applications. It is a pre-analytical device that provides a sample suitable for IVD testing, but it does not perform the diagnostic test itself.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

ORAcollect·Dx is 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 samples collected using ORAcollect-Dx are stabilized and can be transported and/or stored long term at ambient conditions.

Product codes

OYJ

Device Description

The ORAcollect-Dx family of collection devices offers reliable collection, transportation and long-term ambient temperature storage of human DNA from saliva. ORAcollect-Dx is a non-invasive alternative for collecting high quality and quantity human DNA and is suitable for use in molecular diagnostic applications.

ORAcollect-Dx consists of a collection tube containing a stabilizing liquid and a double ended cap with an integrated sponge used to collect a saliva sample. After receiving instruction from a professional, saliva collection can take place in a laboratory setting, physician's office, at home, or in the field. Untrained (naïve) or professional users can carry out saliva collection.

Using the provided instructions for use, the integrated sponge on the device to collect a saliva sample from the mouth. After saliva is collected, the cap is removed from the tube, inverted to place the sponge into the collection tube with the stabilizing liquid, and re-capped with the sponge remaining inside the tube. 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.

ORAcollect-Dx device pre-collection shelf life is 24 months at room temperature (15°C to 25°C) from the date of manufacture. Post collection, ORAcollect·Dx samples are stable at room temperature for up to 60 days. ORAcollect · Dx device and sample integrity are preserved during typical ambient transport and storage conditions.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Saliva samples from the mouth (non-invasive collection)

Indicated Patient Age Range

Not Found

Intended User / Care Setting

For Professional use.
Saliva collection can take place in a laboratory setting, physician's office, at home, or in the field. Untrained (naïve) or professional users can carry out saliva collection.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

REPRODUCIBILITY/PRECISION:

• Sample-to-sample, Lot-to-Lot, day-to-day and operator-to-operator reproducibility:
  • Study Type: Reproducibility study.
  • Sample Size: 10 donors collected 9 saliva samples each over multiple days using three multiple lots of ORAcollect·Dx devices. To evaluate operator reproducibility the same sample was split to generate three (3) replicate samples for each donor.
  • Key Results: All samples met acceptance criteria for DNA concentration (at least 2 ng/μl), total DNA yield (at least 0.01 µg), and A260/A280 ratios (between 1.2 and 2.3). 100% agreement of the eSensor Warfarin Sensitivity Test results with bidirectional sequencing. No DNA Contamination Monitor (DCM) failures and no no-call results. No re-testing required.
• Multi-centre reproducibility:
  • Study Type: Multi-center reproducibility study.
  • Sample Size: 30 donors collected multiple saliva samples each from 3 sites.
  • Key Results: Only one (1) sample did not meet the eSensor Warfarin Sensitivity Saliva Test input requirements. 100% agreement (89/89) with bidirectional sequencing after final pass. Overall, ORAcollect Dx device performance is reproducible from site-to-site, sample-to-sample, day-to-day extraction and operator-to-operator.

SHELF LIFE AND STABILITY:

• Pre-collection shelf-life:
  • Study Type: Shelf life evaluation.
  • Key Results: 100% of ORAcollect-Dx devices stored for at least 24 months at ambient conditions met acceptance criteria for all chemistry endpoints. Storing devices at ambient, room temperature for up to 25 months prior to collection had no significant impact on DNA concentration, yield or A260/A280 ratio. Devices exposed to simulated transport conditions (multiple freeze-thaw cycles between -20°C and 50°C) also showed no degradation in chemical reagents and no significant impact on DNA concentration, yield or A260/A280 ratio.
• Post-collection sample stability:
  • Study Type: Post-collection stability evaluation.
  • Sample Size: 30 donors.
  • Key Results: All samples met acceptance criteria for DNA concentration, yield, A260/A280 ratio, and microbial content. All samples met performance acceptance criteria on the eSensor Warfarin Sensitivity Saliva Test. Supports a post-collection sample stability of 60 days at room temperature and stability upon exposure to typical transport conditions.

DETECTION LIMIT:

• User Study:
  • Study Type: User collection error evaluation.
  • Sample Size: Multiple samples collected from 10 donors for varied collection methods; multiple samples collected from 10 donors for varied collection sites.
  • Key Results: Robustness of the ORAcollect-Dx was demonstrated with all samples (from varied collection methods and incorrect collection sites, except for atypical cheek collection) meeting acceptance criteria for DNA concentration (≥ 2 ng/μ'), total DNA yield (≥ 0.01 µg) and A260/A280 ratio (between 1.2 – 2.3). 100% agreement irrespective of alternative, incorrect collection methods or incorrect collection site after final pass.
• Dry Mouth Study:
  • Study Type: Effect of dry mouth on sample collection.
  • Sample Size: 13 donors with dry mouth.
  • Key Results: 12 of 13 samples met acceptance criteria for the eSensor Warfarin Sensitivity Saliva Testing. 100% agreement with bidirectional sequencing after final pass.

Human Factors:

• Study Type: Compliance to collection instructions and impact on performance.
• Sample Size: Naive donors.
• Key Results: All samples met acceptance criteria for identified critical tasks (Success rate ≥ 80% overall, ≥70% of each task). 100% of samples met acceptance criteria for total DNA yield (≥0.01 µg) and A260/A280 ratio (between 1.2-2.3). At least 99% of samples tested had DNA concentration ≥ 2ng/μL. Minor observed deviations from instructions had no negative impact on device performance.

INTERFERING SUBSTANCES:

• Endogenous Substances:
  • Study Type: Effect of potential interfering endogenous substances.
  • Sample Size: Donors provided 4 samples each, spiked with amylase, hemoglobin, IgA, or total protein.
  • Key Results: 100% agreement for all test substances between the eSensor Warfarin Sensitivity Saliva Test results and DNA sequencing.
• Exogenous Substances:
  • Study Type: Effect of potential interfering exogenous substances.
  • Sample Size: Donors provided 3 samples each for various activity groups (eating, drinking, gum chewing, mouthwash, brushing teeth).
  • Key Results: 100% first-pass agreement of the eSensor Warfarin Sensitivity Saliva Test to bidirectional sequencing when stratified by test substance. Eating, drinking, chewing gum, smoking, mouthwash, and brushing teeth 30 minutes prior to collection does not negatively impact assay performance.

COMPARISON STUDIES:

• Matrix Comparison (OCD-100 vs OCD-100A):
  • Study Type: Analytical performance comparison between device formats.
  • Sample Size: 45 donors.
  • Key Results: 100% of samples collected using OCD-100A met acceptance criteria for DNA concentration (≥ 2ng/μl), total DNA yield (≥ 0.01μg), and A260/A280 ratio (between 1.2 - 2.3). 100% (45/45) final-pass agreement between bi-directional sequencing and the eSensor Warfarin Sensitivity Saliva Test results. The insert in OCD-100A does not impact performance.
• Method Comparison (ORAcollect·Dx with eSensor Warfarin Sensitivity Saliva Test vs bidirectional sequencing):
  • Study Type: Overall analytical performance against "gold standard".
  • Key Results: 100% of samples met acceptance criteria for DNA concentration (≥ 2ng/μl), total DNA yield (≥ 0.01ug), A260/A280 ratio (between 1.2 - 2.3) and performance on the eSensor Warfarin Sensitivity Saliva Test. Final pass results showed 99.4% concordance for genotyping calls with bidirectional sequencing.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found. The document reports "agreement" and "concordance" with bidirectional sequencing for genotyping results.

Predicate Device(s)

Oragene•Dx OGD-500 (K110701)

Reference Device(s)

K152612 (GenMark Diagnostics' eSensor Warfarin Sensitivity Saliva Test)

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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.

Summary

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

2016 May 26,

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

Re: K152464

Trade/Device Name: ORAcollect•Dx OCD-100, ORAcollect•Dx OCD-100A Regulation Number: 21 CFR §862.1675 Regulation Name: Blood specimen collection device Regulatory Class: II Product Code: OYJ Dated: April 18, 2016 Received: April 19, 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 (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 [phone] or [phone] 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 [phone] or [phone] or at its Internet address

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

Sincerely yours.

Courtney

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) K152464

Device Name

ORAcollect.Dx OCD-100; ORAcollect.Dx OCD-100A

Indications for Use (Describe)

ORAcollect Dx is 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 sample sultured using ORAcollect+Dx are stabilized and can be transported and/or stored long term at anbient can adions.

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 Fullerton
Vice President Operations, Quality & Regulatory Affairs
Tel: [phone] Ext. 213, Fax: [phone]
Email: [e-mail]
Device Proprietary Name:	ORAcollect®•Dx
Formats: OCD-100; OCD-100A
Common names:	Kit for collection of human DNA, Saliva kit, Sample collection kit for use in
genetic testing; Swab for collection of human DNA
Proposed Device
Regulatory Classification:	Regulation: 21CFR 862.1675 Blood specimen collection device
Panel: Chemistry (75)
Classification: Class II
Product Code: OYJ DNA Specimen Collection, Saliva
Predicate Device:	Oragene•Dx OGD-500 (K110701)
Regulation: 21CFR 862.1675 Blood specimen collection device
Panel: Chemistry (75)
Classification: Class II
Product Code: OYJ DNA Specimen Collection, Saliva

INTENDED USE

Intended use

ORAcollect·Dx is 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 samples collected using ORAcollect-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 Professional use.

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DEVICE DESCRIPTION

The ORAcollect-Dx family of collection devices offers reliable collection, transportation and long-term ambient temperature storage of human DNA from saliva. ORAcollect-Dx is a non-invasive alternative for collecting high quality and quantity human DNA and is suitable for use in molecular diagnostic applications.

ORAcollect-Dx consists of a collection tube containing a stabilizing liquid and a double ended cap with an integrated sponge used to collect a saliva sample. After receiving instruction from a professional, saliva collection can take place in a laboratory setting, physician's office, at home, or in the field. Untrained (naïve) or professional users can carry out saliva collection.

Using the provided instructions for use, the integrated sponge on the device to collect a saliva sample from the mouth. After saliva is collected, the cap is removed from the tube, inverted to place the sponge into the collection tube with the stabilizing liquid, and re-capped with the sponge remaining inside the tube. 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.

ORAcollect-Dx device pre-collection shelf life is 24 months at room temperature (15°C to 25°C) from the date of manufacture. Post collection, ORAcollect·Dx samples are stable at room temperature for up to 60 days. ORAcollect · Dx device and sample integrity are preserved during typical ambient transport and storage conditions.

SUBSTANTIAL EQUIVALENCE INFORMATION

The following table outlines the similarities and differences between Oragene-Dx and ORAcollect-Dx.

| Principle,
Materials and
Technology | Predicate devices
Oragene-Dx: OGD-500, OGD-
575, OYD-500, OXD-500
(K110701) | Subject devices
ORAcollect-Dx: OCD-100,
OCD-100A (K152556) | 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 | ORAcollect-Dx is 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 samples
collected using ORAcollect-Dx
are stabilized and can be
transported and/or stored
long term at ambient
conditions. | X | |
| Principle,
Materials and
Technology | Predicate devices | Subject devices | Similar | Different |
| | Oragene.Dx: OGD-500, OGD-575, OYD-500, OXD-500
(K110701) | ORAcollect.Dx: OCD-100,
OCD-100A (K152556) | | |
| | stabilized and can be
transported and/or stored long
term at ambient conditions. | | | |
| Special
conditions for
use | Prescription | Prescription | X | |
| Device physical
design | Consists of a collection tube, a
DNA stabilizing liquid and
optional sponges for assisted
collection. | Consists of a tube cap with an
attached integrated sponge
and a collection tube
containing a DNA stabilizing
liquid. | | X |
| Sample source | Human saliva | Human saliva | X | |
| Analyte | Human DNA | Human 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 | |
| Formats | Multiple | Multiple | X | |
| Tube material | Plastic | Plastic | X | |
| Additive | Nucleic acid stabilization
solution | Nucleic acid stabilization
solution | X | |
| Transport and
Stability | Pre-collection Oragene.Dx kits
can be transported at
temperatures ranging from
-20°C to 50°C | Pre-collection ORAcollect.Dx
kits can be transported at
temperatures ranging from
-20°C to 50°C | X | |
| | Post-collection Oragene.Dx
samples can be transported at
temperatures ranging from
-20°C to 50°C | Post-collection ORAcollect.Dx
samples can be transported at
temperatures ranging from
-20°C to 50°C | | |
| | Pre-collection Oragene.Dx kits
can be stored at room
temperature for up to 24
months | Pre-collection ORAcollect.Dx
kits can be stored at room
temperature for up to 24
months | | |
| | Post-collection Oragene.Dx
samples can be stored at room
temperature for up to 12 | Post-collection ORAcollect.Dx
samples can be stored at | | |
| Principle,
Materials and
Technology | Predicate devices
Oragene·Dx: OGD-500, OGD-
575, OYD-500, OXD-500 | Subject devices
ORAcollect.Dx: OCD-100,
OCD-100A (K152556) | Similar | Different |
| | (K110701) | | | |
| | months (OGD-500, OGD-575,
OYD-500) and 3 months for
OXD-525 | room temperature for up to
60 days. | | |
| Performance | Performance has been
established with the eSensor®
Warfarin Sensitivity Saliva Test | Performance has been
established with the eSensor®
Warfarin Sensitivity Saliva Test | × | |

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DNA genotek

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

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The similarities in intended use, materials, technological characteristics show that ORAcollect·Dx is substantially equivalent to Oragene Dx (K110701). The differences tabulated above do not affect the safety and performance of ORAcollect-Dx. Performance of both Oragene-Dx and ORAcollect-Dx devices have been validated using GenMark Diagnostics' FDA cleared eSensor Warfarin Sensitivity Saliva Test.

PERFORMANCE CHARACTERISTICS

REPRODUCIBILITY/PRECISION

Reproducibility of the performance of the ORAcollect Dx device was evaluated to establish multi-center (site-to-site), lot-to-lot, sample-to-sample, day-to-day extraction and operator-to-operator reproducibility.

Sample-to-sample, Lot-to-Lot, day-to-day and operator-to-operator reproducibility

Donors were selected based on their naivety to the ORAcollect·Dx device; none of the donors had used the device previously. A diverse CYP2C9 and VKORC1 genotype distribution was targeted during donor selection.

Ten (10) donors collected nine (9) saliva samples each over multiple days using three multiple lots of ORAcollect·Dx devices. To evaluate operator reproducibility the same sample was split to generate three (3) replicate samples for each donor. Sample replicates were divided equally among three (3) Operators who processed the samples across multiple days. Sample processing consisted of extraction of the DNA using the QlAamp DNA Mini Kit (QIAGEN), followed by the determination of DNA concentration, DNA yield and A260/A280 ratios. Purified DNA was tested using the eSensor Warfarin Sensitivity Saliva Test and results were compared to bi-directional sequencing.

All samples met the study acceptance criteria of DNA concentration of at least 2 ng/μl; total DNA yield of at least 0.01 µg; A260/A80 ratio between 1.2 and 2.3. In first-pass results, there was 100% agreement of the eSensor Warfarin Sensitivity Test results with bidirectional sequencing. There were no DNA Contamination Monitor (DCM) failures and no no-call results. No re-testing of any samples was required. All operators had all samples meet the DNA concentration, yield and A260/A280 ratio acceptance criteria. There was 100% agreement between eSensor Warfarin Sensitivity Test results and bidirectional sequencing.

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Multi-centre reproducibility

Thirty (30) donors collected multiple saliva samples each from 3 sites; 2 of the 3 sites were in a professional setting and had supervised collections compared to unsupervised collections at the third site. The 30 donors were selected to encompass a diverse genotype distribution for CYP2C9 and VKORC1 genotype distribution. After sample collection, one sample from each donor was transported at ambient temperatures to three (3) independent sites. Each site had one operator for a study total of 3 operators. Following sample extraction, all purified genomic DNA samples were tested for DNA concentration and A260/A280 at the sites where they were extracted. All purified genomic DNA samples were transported to Site 1 for testing on the eSensor Warfarin Sensitivity Saliva Test (K152612, GenMark Diagnostics) where 1 extracted DNA aliquot from each sample from each site was tested on the Warfarin assay, excluding a single sample that did not meet assay input criteria.

When data from all 3 sites are combined, only one (1) sample did not meet the eSensor Warfarin Sensitivity Saliva Test input requirements. After final pass there was 100% agreement (89/89) with bidirectional sequencing.

Overall, the conducted reproducibility studies demonstrates that ORAcollect Dx device performance is reproducible from site-to-site, sample-to-sample, day-to-day extraction and operator-tooperator when compared to the predicate device (Oragene-Dx K110701).

SHELF LIFE AND STABILITY

Pre-collection shelf-life

Shelf life conditions were evaluated by using unused ORAcollect-Dx devices stored in real-world storage conditions (i.e. ambient, indoor temperature) and simulated transport conditions.

ORAcollect-Dx devices stored for at least 24 months at ambient, real-world storage conditions were evaluated. 100% of the ORAcollect-Dx devices met the acceptance criteria for all chemistry endpoints. These results demonstrate there is no degradation in the chemical reagents within the device over time when stored at room temperature.

After a minimum of 24 months storage at ambient temperature, ORAcollect Dx devices used to collect samples generated DNA that met all DNA endpoints acceptance criteria. These results demonstrate that storing ORAcollect-Dx devices at ambient, room temperature for up to 25 months prior to collecting samples has no significant impact on the DNA concentration, yield or A260/A280 ratio of the DNA extracted from the sample.

ORAcollect Dx devices exposed to simulated transport conditions (multiple freeze-thaw cycles between -20°C and 50°C) were evaluated. 100% of devices met the acceptance criteria for all chemistry endpoints. These results demonstrate there is no degradation in the chemical reagents when devices are exposed to transport conditions. In addition, 100% of devices met acceptance criteria for evaporation demonstrating no effect of simulated transport conditions on chemistry loss from the device. These results demonstrate there is no degradation in the chemical reagents within the device after transient exposure to temperatures between -20°C and 50°C.

After exposure to simulated transport conditions, all ORAcollect·Dx devices used to collect samples provided DNA that met all DNA endpoints acceptance criteria. These results demonstrate that

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ORAcollect Dx devices can withstand conditions expected to be experienced during typical shipping with no significant impact on the DNA concentration, yield or A260/A280 ratio of the DNA extracted from the sample.

The above supports that ORAcollect Dx devices can be stored for 24 months at ambient, room temperature conditions or exposed to typical transport conditions, with no significant impact on performance.

Post-collection sample stability

This study evaluated post collection stability of ORAcollect·Dx samples stored at room temperature and stability during simulated transport conditions.

Thirty (30) donors provided samples for evaluation of room temperature storage conditions and simulated transport. A total of 120 DNA samples were analyzed for DNA concentration, yield, A260/A280 ratio and microbial content. A subset of samples comprising of samples across all timepoints from 10 donors were tested on the eSensor Warfarin Sensitivity Saliva Tests).

Each time point met the acceptance criteria for DNA concentration, yield and A260/A280 ratio, as 100% of samples in each group had a minimum DNA concentration ≥ 2 ng/μ_ a minimum DNA yield ≥ 0.01 μg, an A260/A280 ratio between 1.2 and 2.3 and no significant difference in mean percent microbial content from baseline.

Overall, all samples met the acceptance criteria for DNA concentration, total DNA yield, A260/A280 ratio and microbial content. All samples met performance acceptance criteria on the eSensor Warfarin Sensitivity Saliva Test.

This data supports a post-collection sample stability of 60 days at room temperature and stability upon exposure to conditions expected during typical transport (i.e. transient exposure to temperatures between -20°C and 50°C).

DETECTION LIMIT

User Study

This study evaluated the effect of sampling variability due to user collection error. Specifically, the study evaluated the effects of incorrect collection methods and the effect of collection from an incorrect site.

Multiple samples were collected from each of ten (10) donors, with each donor using one of the preidentified collection methods for each sample collection. Additionally, multiple samples were collected from each of ten (10) donors, with each donor using one of the pre-identified collection sites for each sample collection. DNA was extracted from each sample using DNA Mini kit (QIAGEN) and performance was evaluated by measuring DNA concentration, total sample DNA yield, A260/A280 ratio and agreement between genotyping results on the eSensor Warfarin Sensitivity Saliva Test (GenMark Diagnostics) and bidirectional sequencing. Study success was evaluated against pre-defined acceptance criteria and performance claims determined based on study data.

Robustness of the ORAcollect-Dx collection device was demonstrated with all samples collected using the varied collected methods meeting the acceptance criteria of DNA concentration ≥ 2 ng/μ'; total

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DNA yield ≥ 0.01 µg and A260/A280 ratio between 1.2 – 2.3. Robustness of the ORAcollect-Dx collection device was also demonstrated with samples collected from an incorrect site in the mouth meeting acceptance criteria of DNA concentration ≥ 2 ng/μl; total DNA yield ≥ 0.01 µg and A260/A280 ratio between 1.2 – 2.3, except in the case of an atypical collection site (cheek), where only 90% of samples had a DNA concentration ≥ 2ng/ul., After final pass there was 100% agreement irrespective of using alternative, incorrect collection methods or incorrect collection site.

Overall, study data supports the robustness of ORAcollect Dx, even in the hands of naive users and/or when instructions for use are not followed properly.

Dry Mouth Study

This study evaluated the effect of dry mouth on the samples collected using the ORAcollect-Dx device and the subsequent effect on eSensor Warfarin Sensitivity Saliva Test as compared to bidirectional sequencing.

Dry mouth refers to the subjective sensation of oral dryness (xerostomia) or hyposalivation, or both -Study participants were selected using a questionnaire to allocate study patients to a xerostomia group '.

Suitable donors identified as experiencing dry mouth were selected, with each donor collecting one (1) sample each using ORAcollect · Dx devices according to the instructions for use.

DNA was extracted from each sample using the QlAamp DNA Mini kit (QIAGEN). Performance was evaluated by measuring DNA concentration and total sample DNA yield using fluorescence and A260/A280 ratio using absorbance. Samples meeting assay input criteria were tested on the eSensor Warfarin Sensitivity Saliva Test, following the procedure in the product insert (PIO200). Performance of ORAcollect Dx device samples on the eSensor Warfarin Sensitivity Saliva Test was evaluated by comparing genotyping results to genotypes determined by bidirectional sequencing and calculating first and final pass percent agreement. Study success was evaluated against pre-defined acceptance criteria (see next section) and performance claims determined based on study data.

Overall, 12 of 13 of samples met acceptance criteria for the eSensor Warfarin Sensitivity Saliva Testing. After Final pass there was 100% agreement with bidirectional sequencing.

Human Factors

This study evaluated compliance to collection instructions and its impact on sample performance, as well as to identify areas of difficulty in the collection procedure. The study evaluated (1) if users can correctly perform the ORAcollection procedure core tasks and evaluate collection performance using DNA concentration, yield and A260/A280 as the endpoint (2) areas of user difficulty or confusion (3) the effects of variable collection instructions procedures on sample quality and device performance.

The user compliance to collection instructions and its impact on sample performance was evaluated by task observation, post-collection follow-up survey, DNA concentration, yield and A260/A280 ratio.

1 Borgnakke WS et al., (Delta Dental Plans Association) (2011). Oral and General Health – Exploring the Connection; Dry mouth (xerostomia): Diagnosis, causes, complications and treatment. Research Review 2011.

² Agha-Hosseini F et al. (2009). Serum and stimulated whole saliva parathyroid hormone in menopausal women with oral dry feeling. Oral Surg Oral Med Oral Pathol Oral Radiol Endo. 107: 806-810.

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Naive donors were recruited for the study. Study staff provided oral instructions from the package insert and the donor was handed an ORAcollect-Dx collection kit. In addition, donors were asked to complete the sample collection following the instructions for use on the oral instructions provided by the study staff, including intentionally varied collection for the critical tasks. Study staff observed the collections and asked pre-determined post-collection follow-up questions to each donor to provide the subject the opportunity to explain any core tasks that they completed incorrectly. The results from the observations were tallied for each donor. All samples were analyzed for DNA concentration and yield to assess the impact of instruction compliance on collection performance.

Overall, all samples met the acceptance criteria for the identified critical tasks; Success rate ≥ 80% overall (all tasks combined) and ≥70% of each task. 100% of samples met acceptance criteria for total DNA yield ≥0.01 µg and A260/A280 ratio between 1.2-2.3. At least 99% of samples tested had DNA concentration ≥ 2ng/μL. This demonstrates that even in cases when donors deviated from core tasks or when they did not follow instructions, >99% of all samples tested still met acceptance criteria. Further, study data shows that minor observed deviations from the collection instructions had no negative impact on device performance.

INTERFERING SUBSTANCES

Endogenous Substances

This study evaluated the effect of analytical specificity of the ORAcollect·Dx device by examining the effects of potential interfering endogenous substances on performance.

Donors provided four (4) ORAcollect·Dx samples each which were each spiked with one of the four interfering substances: amylase, hemoglobin, IgA and total protein (composed of IgA, amylase and albumin). Three extractions were performed on each sample using the QlAamp DNA Mini DNA kit (QIAGEN) and performance was evaluated by measuring DNA concentration, total sample DNA yield, A260/A280 ratio and agreement between genotyping results on the eSensor Warfarin Sensitivity Salva Test and bidirectional sequencing. Study success was evaluated against pre-defined acceptance criteria and performance claims determined based on study data.

When results were stratified by test substance, there was 100% agreement for all test substances between the eSensor Warfarin Sensitivity Saliva Test results and DNA sequencing.

Exogenous Substances

This study evaluated the effect of analytical specificity of the ORAcollect Dx device by examining the effects of potential interfering exogenous substances on performance.

For each exogenous substance test group (eating, drinking, gum chewing, mouthwash, brushing teeth), each donor provided three samples including up to 30 minutes post-activity. Each sample was extracted in triplicate, all DNA samples which were analyzed for DNA concentration, DNA yield and A260/A280 ratio. One extraction replicate per sample was tested on the eSensor Warfarin Sensitivity Saliva Test, for a total of 129 genotyping tests.

Overall, when results were stratified by test substance, there was 100% first-pass agreement of the eSensor Warfarin Sensitivity Saliva Test to bidirectional sequencing. The eSensor Warfarin Sensitivity Saliva Test results support that Eating, Drinking, Chewing Gum, Smoking, Mouthwash, and Brushing

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teeth 30 minutes prior to collection of samples with ORAcollect Dx does not have any negative impact on assay performance.

COMPARISON STUDIES

Matrix Comparison

ORAcollect-Dx device is available in two equivalent and identical formats; OCD-100 and OCD-100A. The OCD-100A format includes a molded plastic insert inside the collection tube. The insert is intended to facilitate or enable a more efficient physical handling of the laboratory but has no impact on sample collection. This study evaluated the analytical performance of samples collected using the OCD-100A device when compared to the performance of samples collected using OCD-100.

Forty-five (45) donors provided 1 sample each using OCD-100A format and following typical instructions. All donors were naïve to collecting samples using OCD-100A. DNA was extracted from each sample using the QlAamp DNA Mini kit (QIAGEN). Performance was evaluated by measuring DNA concentration, DNA vield and A260/A280 ratio. Performance of samples on the eSensor Warfarin Sensitivity Salva Test was evaluated by comparing genotyping results to genotypes determined by bidirectional sequencing and calculating first and final pass percent agreement.

Study results showed that 100% of samples collected using OCD-100A format met acceptance criteria for DNA concentration ≥ 2ng/μl, total DNA yield ≥ 0.01μg, and A260/A280 ratio between 1.2 - 2.3. There was 100% (45/45) final-pass agreement between bi-directional sequencing and the eSensor Warfarin Sensitivity Saliva Test results.

When compared to results obtained with samples collected by the same donors using the OCD-100 format, study data indicates that the insert present in the OCD-100A format does not impact the performance of the device and eSensor Warfarin Sensitivity Saliva Test results. Both OCD-100 and OCD-100A formats met acceptance criteria for DNA concentration ≥ 2ng/ul, total DNA yield ≥ 0.01µg, and A260/A280 ratio between 1.2 - 2.3.

Method Comparison

This study evaluated the overall analytical performance of ORAcollect·Dx samples on the eSensor Warfarin Sensitivity Saliva Test. Genotyping results on the eSensor Warfarin Sensitivity Saliva Test were compared to results from the 'gold standard' bidirectional sequencing in order to assess performance.

Overall, 100% of samples met acceptance criteria for DNA concentration ≥ 2ng/μl, total DNA yield ≥ 0.01ug, A260/A280 ratio between 1.2 - 2.3 and performance on the eSensor Warfarin Sensitivity Saliva Test. The final pass results indicated that the genotyping calls by the eSensor Warfarin Sensitivity Saliva Test method were 99.4% concordant with genotypes determined by bidirectional sequencing for all polymorphisms.

See GenMark Diagnostic's eSensor Warfarin Sensitivity Saliva Test submission (K152612).

CONCLUSION

The submitted information in this premarket notification is complete and supports the safety and effectiveness of the ORAcollect-Dx device family and that the ORAcollect-Dx collection device is substantially equivalent to the predicate device (Oragene·Dx K110701).