Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on standard molecular biology techniques (PCR, fluorescent probe detection) and automated processes for DNA analysis and genotype determination. There is no mention of AI, ML, or algorithms that learn from data.

Therapeutic

No.
This device is an in vitro diagnostic test used to determine a patient's CYP2C19 genotype, which aids clinicians in selecting therapeutic strategies. It does not directly provide therapy or treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states, "The Spartan RX CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3 and *17 genotype..." This directly classifies it as a diagnostic device.

SaMD (Software as a Medical Device)

No

The device description explicitly states it is a "sample-to-result DNA testing system" comprised of a "Spartan RX Platform" and "Spartan RX CYP2C19 Assays," and involves physical processes like DNA extraction, PCR, and fluorescent signal detection using an "Spartan RX Analyzer instrument." This indicates significant hardware components beyond just software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use/Indications for Use: The document explicitly states "The Spartan RX CYP2C19 System is a qualitative in vitro diagnostic test..." and describes its use for identifying a patient's genotype from a biological sample (buccal swab). It also states it is for "prescription use only," which is common for IVDs.
Device Description: The description details a system that performs DNA extraction, amplification, detection, and analysis from a biological sample to determine a genotype. These are all processes typical of an in vitro diagnostic device.
Performance Studies: The document includes detailed performance studies (Limit of Detection, Method Comparison, Inter-Laboratory Reproducibility, Reagent Lot-to-Lot Reproducibility, Exogenous and Endogenous Interfering Substances) which are required for the validation of an IVD.
Predicate Device: The mention of a "Predicate Device(s)" with a K number (K101683; INFINITI CYP2C19 Assay) strongly indicates that this device is being submitted for regulatory review as an IVD, as predicate devices are used for comparison in the regulatory process for new IVDs.

All of these points align with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Spartan RX CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3 and *17 genotype determined from genomic DNA obtained from a buccal swab sample. For prescription use only.

Spartan RX CYP2C19 Assay - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Assay will be run on the Spartan RX CYP2C19 Platform from the buccal sample collected with a buccal swab. The Spartan RX CYP2C19 Assay is not indicated to be used to predict drug response or non-response.

Spartan RX CYP2C19 Platform - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Platform will be used to run the Spartan RX CYP2C19 Assay.

Product codes (comma separated list FDA assigned to the subject device)

NTI, NSU

Device Description

The Spartan RX CYP2C19 System is a sample-to-result DNA testing system that uses proprietary technology to integrate DNA extraction and amplification. Genotypes are determined using PCR and fluorescent probe detection. The Spartan RX CYP2C19 System is comprised of the Spartan RX liadrooom prable a and Spartan RX CYP2C19 Assays. The Spartan RX CYP2C19 Assays are run on the Spartan RX CYP2C19 Platform.

The Spartan RX CYP2C19 System is based on the following processes:

Buccal swab collection i.
ii. DNA extraction
PCR-based amplification of the target gene lii.
Detection of the *2, *3, and *17 alleles using fluorescent-probes iv.
Fluorescent signal detection and analysis V.
Genotype determination vi.

The Spartan RX CYP2C19 System integrates and automates steps ii to vi. Results are presented to the end user as genotype calls. The system also has integrated controls that monitor performance of a run and automatically inform the user of any anomalies in the instrument or reagents.

The system detects the CYP2C19 *2, *3, and *17 genotypes in separate reagent tubes. The operator collects buccal swab samples from a patient; inserts each sample into a reagent tube; and then inserts the reagent tubes into a Spartan RX Analyzer instrument.

Spartan RX CYP2C19 Platform:

a) The SPARTAN RX ANALYZER is a thermal cycling instrument that automates polymerase chain reaction (PCR) amplification of the target gene, fluorescence-based detection of CYP2C19 alleles, and genotype calling.
The NETBOOK serves as the user interface for logging in to the Spartan RX Platform, inputting b) patient information, and starting a test.
The PRINTER automatically prints the genotype results after the Spartan RX Platform finishes c) performing the Spartan RX CYP2C19 Assays.
d) The BARCODE SCANNER is used to automatically enter SCK and ECK lot numbers into the Spartan RX Platform.

Spartan RX CYP2C19 Assays:
The Spartan RX CYP2C19 Assays are the consumable components of the Spartan RX CYP2C19 System. There are two different types of assay-each type is described in detail below.

a) SAMPLE COLLECTION KITS (SCKs) contain the consumables required to determine a patient's CYP2C19*2, *3, or *17 genotype. There are three types of SCKs, specific for the *2, *3, or *17 alleles. Each SCK consists of the following components:
- POUCH, containing labeling information to ensure traceability (lot number, manufacturing date, and expiry date) and two compartments (for the buccal swab and reagent tube). The pouch also includes a barcode that is compatible with a standard reader.
- BUCCAL SWAB, used to collect a buccal sample from the inside of a patient's cheek and transfer it into the reagent tube.
- REAGENT TUBE, containing chemicals for DNA extraction, PCR amplification, and fluorescent detection of the specific CYP2C19 allele.
- The SCKs are color-coded to indicate which CYP2C19 allele they are designed to detect.
  - BLUE = *2
  - WHITE = *3
  - BLACK = *17
b) EXTERNAL CONTROL KITS (ECKs) contain the consumables required to determine if the Spartan RX Platform and reagents are performing correctly. Each ECK consists of the following components:
- POUCH, containing labeling information to ensure traceability (lot number, manufacturing date, and expiry date).
- REAGENT TUBE, containing synthetic nucleic acid control and chemicals for PCR amplification and fluorescent detection of the specific CYP2C19 allele.
- The ECKs are color-coded to indicate which reagent they control for.
  - BLUE = *2
  - WHITE = *3
  - BLACK = *17
- The ECKs have been modified so that the tube cannot be opened. They are meant to be put directly into the analyzer without adding or removing anything from them.

Spartan RX Accessories:
The SAMPLE TRANSPORT SYSTEM is an insulated transport bag that contains a polystyrene box and a Cold Block. The Transport System is designed to keep the SCKs cold as they are moved from the freezer to the patient and from the patient to the Spartan RX Analyzer. The Transport System is provided with purchase of the platform and is to be used for all tests.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Buccal swab sample (from buccal cells/inside of a patient's cheek)

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Clinicians (clinical laboratories) / Prescription use only

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)

Limit of Detection (Analytical Sensitivity)

Study Type: Analytical Sensitivity / Limit of Detection Study
Sample Size:
- Part 1: 100 individual buccal swabs collected from 40 different individuals by 11 different operators.
- Part 2: 52 replicates each of buccal swab samples collected from *1/*1, *2/*17, *17/*17, and *2/*3 individuals. Total of 260 tests.
Key Results:
- Table 2a (First Pass):
  - 5 pooled swabs: 84.6% correct calls (95% CI 75%)
  - 2 pooled swabs: 100.0% correct calls (95% CI 95%)
  - Normal Swab: 98.1% correct calls (95% CI 92%)
  - 1 Half Stroke: 98.1% correct calls (95% CI 92%)
  - Inside Mouth Touch: 84.6% correct calls (95% CI 75%)
  - The first pass correct call rate at input levels lower than 0.1 swabs per test was 84.6%.
- Table 2b (Second Pass): All categories showed 98.1% or 100.0% correct calls, with 95% CI of 92% or 95%.
- Experiment indicates that excessively high or low amounts of buccal material can lead to "No call" results or internal control aborts. Proper swabbing technique is important.

Method Comparison

Study Type: Method Comparison
Sample Size: 327 samples initially, 325 included in analysis. 4 samples re-tested for second pass.
Data Source: Samples deidentified. Genomic DNA extracted from saliva samples and compared to bi-directional sequencing.
Annotation Protocol: Not specified beyond bi-directional sequencing.
Key Results:
- First Pass (Table 3a): Overall correct call rate was 98.8% (95% CI 97%), with 4 "No call" results. No incorrect calls.
- Second Pass (Table 3b): All 4 "No call" samples were re-tested and called correctly. Overall correct call rate was 100.0% (95% CI 99%). No incorrect calls.
- For the Transport System, first pass results ranged from 105/106 to 109/110. All results were 100% on the second pass.

Inter-Laboratory Reproducibility

Study Type: Inter-Laboratory Reproducibility
Sample Size: Buccal swab samples from 8 individuals (one per genotype) across three sites. Two operators per site. Tests performed across five non-consecutive days, two sessions per day. Each individual tested once per sub-session by each operator. Total of 960 tests.
Data Source: Genotypes of individuals confirmed by bi-directional sequencing.
Annotation Protocol: Not specified beyond bi-directional sequencing for genotype confirmation.
Key Results:
- First Pass (Table 4a): Overall correct call rate was 98.9% (95% CI 98%), with 10 "No call" results and 1 incorrect call.
- Second Pass (Table 4b): Overall correct call rate was 99.8% (95% CI 99%). After second pass, all but 1 of the 10 No calls were recovered, resulting in 1 No call and 1 incorrect call overall. The incorrect call's root cause could not be conclusively determined.

Reagent Lot-to-Lot Reproducibility

Study Type: Reagent Lot-to-Lot Reproducibility
Sample Size: Not explicitly stated, but derived from the tables: 107 samples for Lot 1, 106 for Lot 2, 107 for Lot 3.
Data Source: Not specified, but uses three independent lots of each reagent type.
Key Results:
- First Pass (Table 5a):
  - Lot 1: 97% correct calls (95% CI 93%), with 3 "No call" results.
  - Lot 2: 100% correct calls (95% CI 98%), with 0 "No call" results.
  - Lot 3: 100% correct calls (95% CI 98%), with 0 "No call" results.
- Second Pass (Table 5b): All 3 "No call" samples from the first pass were successfully called on the second pass. All lots showed 100% correct calls (95% CI 98% or 99%). Results indicate that different reagent lots perform equivalently.

Exogenous and Endogenous Interfering Substances

Study Type: Interference Study (Exogenous and Endogenous Interfering Substances)
Sample Size: 16 samples tested for each of 14 substances (n=4 per genotype tested). Total of 224 tests.
Data Source: Buccal swab samples from *1/*1, *2/*17, *17/*17, and *2/*3 individuals, confirmed by bi-directional sequencing.
Annotation Protocol: Not specified beyond bi-directional sequencing for genotype confirmation.
Key Results:
- First Pass (Table 6a): Overall correct call rate was 91.5% (95% CI 88%), with 19 "No call" results. Toothpaste had a particularly low correct call rate (31.3%) and high "No calls" (11).
- Second Pass (Table 6b): Overall correct call rate was 99.55% (95% CI 98%), with 1 "No call" result. For toothpaste, 15 samples were correct out of 16, with 1 no call remaining. All other substances achieved 100% correct calls. The remaining No call for toothpaste was due to the subject not rinsing thoroughly.

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

Limit of Detection (Analytical Sensitivity): Correct call rates ranged from 84.6% to 100% on first pass, and 98.1% to 100% on second pass.
Method Comparison: First pass correct call rate of 98.8%, second pass correct call rate of 100%. No incorrect calls.
Inter-Laboratory Reproducibility: First pass correct call rate of 98.9%, second pass correct call rate of 99.8%. One incorrect call overall.
Reagent Lot-to-Lot Reproducibility: First pass correct call rates from 97% to 100%. Second pass correct call rates of 100% for all lots. (95% one-sided confidence lower limit provided for all).
Exogenous and Endogenous Interfering Substances: First pass correct call rate of 91.5%, second pass correct call rate of 99.55%.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

INFINITI CYP2C19 Assay, 510(k) Number K101683

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.3360 Drug metabolizing enzyme genotyping system.

(a)
Identification. A drug metabolizing enzyme genotyping system is a device intended for use in testing deoxyribonucleic acid (DNA) extracted from clinical samples to identify the presence or absence of human genotypic markers encoding a drug metabolizing enzyme. This device is used as an aid in determining treatment choice and individualizing treatment dose for therapeutics that are metabolized primarily by the specific enzyme about which the system provides genotypic information.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Drug Metabolizing Enzyme Genotyping Test System.” See § 862.1(d) for the availability of this guidance document.

Summary

0

510(k) Summary

Submitter Name:	Spartan Bioscience Inc.
Address:	Suite 204, 6 Gurdwara Rd
Ottawa, Ontario, Canada K2E 8A3
1 (613) 228-7756
Contact:	Dr. Chris Harder
VP Diagnostics
Phone:	1 (613) 228-7756
E-mail:	chris.harder@spartanbio.com
Date Prepared:	Aug 9th, 2013
Device Trade Name:	Spartan RX TM CYP2C19 System
For the assay: Spartan RX CYP2C19 Assay
For the platform: Spartan RX CYP2C19 Platform
Device Common Name:	Drug metabolizing enzyme genotyping assay
Measurand:	CYP450 2C19 2, 3, *17
Sample Type:	DNA from buccal cells
Technology:	Polymerase Chain Reaction (PCR)
Device Panel:	Chemistry and Toxicology
Classification Name:	Drug metabolizing enzyme genotyping system, 862.3360
Instrumentation for clinical multiplex test systems, 862.2570
Classification Code:	NTI: Drug metabolizing enzyme genotyping system
NSU: Instrumentation for clinical multiplex test systems
Predicate Device:	INFINITI CYP2C19 Assay, 510(k) Number K101683
Classification Code: NTI and NSU, Regulation No. 862.3360 and
862.2570

Intended Use

The Spartan RX CYP2C19 System is a qualitative in vitro diagnostic test for the identification of a patient's CYP2C19 *2, *3 and *17 genotype determined from genomic DNA obtained from a buccal swab sample. For prescription use only.

Indication for Use

Spartan RX CYP2C19 Assay - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Assay will be run on the Spartan RX CYP2C19 Platform from the buccal sample collected with

1

a buccal swab. The Spartan RX CYP2C19 Assay is not indicated to be used to predict drug response or non-response.

Spartan RX CYP2C19 Platform - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Platform will be used to run the Spartan RX CYP2C19 Assay.

Device Description

The Spartan RX CYP2C19 System is a sample-to-result DNA testing system that uses proprietary technology to integrate DNA extraction and amplification. Genotypes are determined using PCR and fluorescent probe detection. The Spartan RX CYP2C19 System is comprised of the Spartan RX liadrooom prable a and Spartan RX CYP2C19 Assays. The Spartan RX CYP2C19 Assays are run on the Spartan RX CYP2C19 Platform.

The Spartan RX CYP2C19 System is based on the following processes:

Buccal swab collection i.
ii. DNA extraction
PCR-based amplification of the target gene lii.
Detection of the *2, *3, and *17 alleles using fluorescent-probes iv.
Fluorescent signal detection and analysis V.
Genotype determination vi.

The Spartan RX CYP2C19 System integrates and automates steps ii to vi. Results are presented to the end user as genotype calls. The system also has integrated controls that monitor performance of a run and automatically inform the user of any anomalies in the instrument or reagents.

The system detects the CYP2C19 *2, *3, and *17 genotypes in separate reagent tubes. The operator collects buccal swab samples from a patient; inserts each sample into a reagent tube; and then inserts the reagent tubes into a Spartan RX Analyzer instrument.

Spartan RX CYP2C19 Platform

There are four components of the Spartan RX CYP2C19 Platform.

a) The SPARTAN RX ANALYZER is a thermal cycling instrument that automates polymerase chain reaction (PCR) amplification of the target gene, fluorescence-based detection of CYP2C19 alleles, and genotype calling.
The NETBOOK serves as the user interface for logging in to the Spartan RX Platform, inputting b) patient information, and starting a test.
The PRINTER automatically prints the genotype results after the Spartan RX Platform finishes c) performing the Spartan RX CYP2C19 Assays.
d) The BARCODE SCANNER is used to automatically enter SCK and ECK lot numbers into the Spartan RX Platform.

Spartan RX CYP2C19 Assays

The Spartan RX CYP2C19 Assays are the consumable components of the Spartan RX CYP2C19 System. There are two different types of assay-each type is described in detail below.

a) SAMPLE COLLECTION KITS (SCKs) contain the consumables required to determine a patient's CYP2C19*2, *3, or *17 genotype. There are three types of SCKs, specific for the *2, *3, or *17 alleles. Each SCK consists of the following components:

2

POUCH, containing labeling information to ensure traceability (lot number, manufacturing date, and expiry date) and two compartments (for the buccal swab and reagent tube). The pouch also includes a barcode that is compatible with a standard reader.
BUCCAL SWAB, used to collect a buccal sample from the inside of a patient's cheek and transfer it into the reagent tube.
REAGENT TUBE, containing chemicals for DNA extraction, PCR amplification, and fluorescent detection of the specific CYP2C19 allele.

The SCKs are color-coded to indicate which CYP2C19 allele they are designed to detect.

BLUE = *2 י
WHITE = *3 ・
BLACK = *17
b) EXTERNAL CONTROL KITS (ECKs) contain the consumables required to determine if the Spartan RX Platform and reagents are performing correctly. Each ECK consists of the following components:
- POUCH, containing labeling information to ensure traceability (lot number, manufacturing date, and expiry date).
- REAGENT TUBE, containing synthetic nucleic acid control and chemicals for PCR amplification and fluorescent detection of the specific CYP2C19 allele.

The ECKs are color-coded to indicate which reagent they control for.

BLUE = *2 ・
- WHITE = *3
- BLACK = *17

The ECKs have been modified so that the tube cannot be opened. They are meant to be put directly into the analyzer without adding or removing anything from them

Spartan RX Accessories

The SAMPLE TRANSPORT SYSTEM is an insulated transport bag that contains a polystyrene box and a Cold Block. The Transport System is designed to keep the SCKs cold as they are moved from the freezer to the patient and from the patient to the Spartan RX Analyzer. The Transport System is provided with purchase of the platform and is to be used for all tests..

Substantial Equivalence Discussion

The Spartan RX CYP2C19 System uses the same fundamental scientific technologies, and has a similar intended use, as that of the predicate device-the INFINITI CYP2C19 Assay. The table below provides a comparison of the Spartan RX CYP2C19 System and the predicate device. The comparison demonstrates that the Spartan RX CYP2C19 System is substantially equivalent to the predicate device.

Table 1 – Comparison of the Spartan RX CYP2C19 System to the predicate device

| Characteristic | Predicate Device
INFINITI CYP2C19 Assay
(K101683) | Subject Device
Spartan RX CYP2C19 System |
|-----------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Similarities | |
| Intended Use | The INFINITI CYP2C19 Assay is an in
vitro diagnostic test for the
identification of a
patient's CYP450 2C19 genotype in
genomic deoxyribonucleic acid (DNA)
obtained from
EDTA-anticoagulated whole blood
samples. The INFINITI CYP2CI9 | The Spartan RX CYP2C19 System is a
qualitative in vitro diagnostic test for the
identification of a patient's CYP2C19 *2,
*3 and *17 genotype determined from
genomic DNA obtained from a buccal
swab sample. For prescription use only. |
| Characteristic | Predicate Device
INFINITI CYP2C19 Assay
(K101683) | Subject Device
Spartan RX CYP2C19 System |
| | Assay is a qualitative
assay for use in clinical laboratories
upon prescription by the attending
physician. | |
| Indication for Use | The INFINITI CYP2C19 Assay is
indicated for use as an aid to clinicians
in determining
therapeutic strategy for therapeutics
that are metabolized by the CYP450
2C19 gene product,
specifically *2, *3, * 17.
The INFINITI CYP2C19 Assay is not
indicated to be used to predict drug
response or nonresponse. | Spartan RX CYP2C19 Assay - The
Spartan RX CYP2C19 System is
indicated for use as an aid to clinicians in
determining therapeutic strategies for
therapeutics that are metabolized by the
Cytochrome P450 2C19 gene product,
and that are specifically affected by the
*2, *3, and *17 alleles. The Spartan RX
CYP2C19 Assay will be run on the
Spartan RX CYP2C19 Platform from
the buccal sample collected with a
buccal swab. The Spartan RX
CYP2C19 Assay is not indicated to be
used to predict drug response or non-
response.

Spartan RX CYP2C19 Platform - The
Spartan RX CYP2C19 System is
indicated for use as an aid to clinicians in
determining therapeutic strategies for
therapeutics that are metabolized by the
Cytochrome P450 2C19 gene product,
and that are specifically affected by the
*2, *3, and *17 alleles. The Spartan RX
CYP2C19 Platform will be used to run
the Spartan RX CYP2C19 Assay. |
| Limitations | Not intended to be used to predict drug
response or non-response. | Same |
| DNA Sequence | Detects specific DNA sequences
through recognition of DNA targets
with fluorescence. | Same |
| Technology | Utilizes thermal cycling and target
DNA amplification. | Same |
| Assay Results | Assay signal results are interpreted by
a software program.
Assay results are provided as
genotype calls reported to the end
user in a report format. | Same |
| Target Gene | CYP4502C19 *2, *3, and *17. | Same |
| | | Differences |
| Specimen Type | Purified DNA from EDTA-anti-
coagulated whole blood sample. | Unpurified DNA from a buccal swab
sample. |
| Platform | Microarray-based genotyping test for
simultaneous (multiplex system) of
DNA sequences. | Fluorescent-probe PCR-based
genotyping test for multiplex analysis of
DNA sequences. |
| | | Trial Calling Rates |
| Reproducibility (%
agreement/ 95%
Lower CI) | 96.9% / 95.6% | 99.8% / 99.4% |
| Method comparison
(% agreement/ 95%
Lower CI) | 100.0% / 99.8% | 100.0% / 99.2% |

3

ﻓ

4

Performance

Limit of Detection (Analytical Sensitivity)

The input material for the Spartan RX CYP2C19 System is a buccal swab collected from an individual, r his inserted directly into the reagent tube without any requirement for the user to extract or purify White for this reason, the limit of detection (LOD) study was to determine if the Spartan DIV. For the Peacer, In Super of target material amounts collected in typical buccal swabs. The study was conducted in two parts.

Part 1 involved the determination of a relative measure of the amount of DNA present in 100 individual buccal swabs, collected from 40 different individuals by 11 different operators. These operators had laboratory - and non-laboratory backgrounds. The mean DNA amount was deemed to be equivalent to one "typical" swab and all measurements were normalized to this value and presented as the number of swab equivalents.

Part 2 assessed the analytical sensitivity (limit of detection) by analyzing buccal swab samples collected from *1, *2/*17, *17/*17, and *2/*3 individuals. Five DNA collection conditions were used: 5 pooled huccal swabs; 2 pooled buccal swabs; a normal buccal swab; a single downward stroke (1 half stroke); butter wabs, if police based to the inside of the mouth. Replicates of 52 samples were performed for and condition. Results are summarized in Tables 2a and 2b. In parallel, the amount of DNA in the swabs was quantified using SYBR Green (standard curve), and this value was translated to the corresponding number of swabs relative to the mean of the population determined in Part 1.

| Test
Condition | Genotypea | #
Samples
tested | #
Correct
callsb | #
Incorrect
calls | # No calls | %
Correct
calls | 95% One-
sided
confidence
lower limit) |
|-----------------------|------ | 5 pooled
swabs | *1/*1 | 13 | | *17/*17 | 13 | | *2/*3 | | *2/*17 | 13 | | Total | 2 pooled
swabs | *1/*1 | 13 | | *17/*17 | 13 | | *2/*3 | | *2/*17 | 13 | | Total | Normal Swab | *1/*1 | | *17/*17 | 13 | | *2/*3 | | *2/*17 | 13 | | Total | 1 Half Stroke | *1/*1 | | *17/*17 | 13 | | *2/*3 | | *2/*17 | 13 | | Total | Inside Mouth
Touch | *1/*1 | 13 | | *17/*17 | 13 | | *2/*3 | | *2/*17 | 13 | | Total -----|------------------------|------------------------|-------------------------|------------|-----------------------|-------------------------------------------------|
| 11 | 0 | 2 | 84.6% | 63% |
| 12 | 0 | 1 | 92.3% | 72% |
| 13 | 8 | 0 | 5 | 61.5% | 40% |
| 13 | 0 | 0 | 100.0% | 83% |
| 52 | 44 | 0 | 8 | 84.6% | 75% |
| 13 | 0 | 0 | 100.0% | 83% |
| 13 | 0 | 0 | 100.0% | 83% |
| 13 | 13 | 0 | 0 | 100.0% | 83% |
| 13 | 0 | 0 | 100.0% | 83% |
| 52 | 52 | 0 | 0 | 100.0% | 95% |
| 13 | 13 | 0 | 0 | 100.0% | 83% |
| 13 | 0 | 0 | 100.0% | 83% |
| 13 | 12 | 0 | 1 | 92.3% | 72% |
| 13 | 0 | 0 | 100.0% | 83% |
| 52 | 51 | 0 | 1 | 98.1% | 92% |
| 13 | 12 | 0 | 1 | 92.3% | 72% |
| 13 | 0 | 0 | 100.0% | 83% |
| 13 | 13 | 0 | 0 | 100.0% | 83% |
| 13 | 0 | 0 | 100.0% | 83% |
| 52 | 51 | 0 | 1 | 98.1% | 92% |
| 10 | 0 | 3 | 76.9% | 54% |
| 12 | 0 | 1 | 92.3% | 72% |
| 13 | 9 | 0 | 4 | 69.2% | 46% |
| 13 | 0 | 0 | 100.0% | 83% |
| 52 | 44 | 0 | 8 | 84.6% | 75% |

Table 2a - Limit of Detection - FIRST PASS

Genotyped by bi-directional sequencing; 1/ 1 samples are wild-type for *2, *3, and *17.

" uniteryped by br arcolibrar ocquently of all, results of all three genotypes (*2, *3, *17) had to be correct.

in three for a sample to be doomied a cerrest can increased rate of No calls and Internal Control Errors.

5

| Test
Condition | Genotypea | #
Samples
tested | #
Correct
callsb | #
Incorrect
calls | # No calls | %
Correct
calls | 95% One-sided
confidence
lower limit) |
|-----------------------|-----------|------------------------|------------------------|-------------------------|------------|-----------------------|---------------------------------------------|
| 5 pooled
swabs | *1/*1 | 13 | 12 | 0 | 1 | 92.3% | 72% |
| | *17/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*3 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| Total | | 52 | 51 | 0 | 1 | 98.1% | 92% |
| 2 pooled
swabs | *1/*1 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *17/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*3 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| Total | | 52 | 52 | 0 | 0 | 100.0% | 95% |
| Normal Swab | *1/*1 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *17/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*3 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| Total | | 52 | 52 | 0 | 0 | 100.0% | 95% |
| 1 Half Stroke | *1/*1 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *17/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*3 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| Total | | 52 | 52 | 0 | 0 | 100.0% | 95% |
| Inside Mouth
Touch | *1/*1 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *17/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*3 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| | *2/*17 | 13 | 13 | 0 | 0 | 100.0% | 83% |
| Total | | 52 | 52 | 0 | 0 | 100.0% | 95% |

1 Genotype by bi-directional sequencing; *1,*1 samples are wild-type for *2, *3, and *17.

" Genotype by brunes moral soquenting," 1) " bainpies is of all three genotypes (*2, *3, *17) had to be correct.

The first pass correct call rate at input levels lower than 0.1 swabs per test was 84.6%. Therefore, the The first pass correct can face at mput levels lower than b. Towals por too may be has was new teet.

6

Relationship between # Swabs across population & amount of collected material using various swabbing techniques

Image /page/6/Figure/2 description: This image is a graph that plots the number of swabs in a sample versus the sample number. The y-axis, labeled "NUMBER OF SWABS IN SAMPLE", ranges from 0.0 to 4.0. There are also horizontal lines indicating different levels: 3.3 ng, 1.6 ng, 1.3 ng, 0.6 ng, and 0.1 ng. The graph also includes a legend indicating different types of swabs: 5 Pooled Swabs, 2 Pooled Swabs, Normal Swab, One Half Stroke, and Inside Mouth Touch.

Figure 1 – Relationship between the normal swab population & the amount of material collected using the various swabbing techniques as outlined in the protocol. The corresponding average amount of genomic DNA (ng) collected using each swabbing technique is indicated on the right side of the graph.

These experiments indicate that there are two consequences when excessively high or low amounts of buccal material are collected. Either the system generates an internal control abort (Positive System Control fail) or the system generates a No call result. To avoid these consequences, the Instructions for Ountrol half of the applied is swab firmly with 3x up-and-down strokes. Based on these results, proper swabbing is an important factor that influences the rate of No call results. Also, the results from Part 3 demonstrated the system's lower limit of detection when using genomic DNA. The recommended quantity of DNA for external controls was based on these results.

Method Comparison

The Spartan RX CYP2C19 System was compared to bi-directional sequencing. Samples were deidentified to protect patient identity. Genomic DNA was extracted from saliva samples. If the result of the first test for a particular individual was a No call, the test was repeated (second pass).

The Method Comparison study was performed by 10 operators at three different locations. The operators had no previous swabbing experience. Of the 327 samples tested, sequencing was unsuccessful for 2 samples these samples were excluded from the analysis. Of the 325 samples included in the analysis, 4 samples gave a No call result on the first pass test and were re-tested. After the second pass, all samples were called correctly. No samples were called incorrectly. The overall correct call rate for the first pass and second pass tests was 98.8% and 100%, respectively.

For this study, 1/3 of samples collected were tested immediately (4 minutes pre-swabbing and 8 minutes post-swabbing); 1/3 were tested after 10 minutes (4 minutes pre-swabbing and 10 minutes postswabbing); and 1/3 were tested after 60 minutes (45 minutes pre-swabbing and 60 minutes post swabbing) of storage in the Sample Transport System after swab insertion.

Results of first and second pass tests are summarized in Tables 3a and 3b, respectively.

7

| Genotypea | #
Samples
tested | #
Correct
Callsb | #
Incorrect
calls | # No calls | %
Correct
calls | 95% One-
sided
confidence
lower limit |
|-----------|------------------------|------------------------|-------------------------|------------|-----------------------|------------------------------------------------|
| *1/*1 | 130 | 128 | 0 | 2 | 98.5% | 95% |
| *1/*2 | 95 | 94 | 0 | 1 | 98.9% | 95% |
| *2/*2 | 19 | 19 | 0 | 0 | 100.0% | 88% |
| *1/*3 | 7 | 7 | 0 | 0 | 100.0% | 72% |
| *3/*3 | 1 | 1 | 0 | 0 | 100.0% | 27% |
| *1/*17 | 40 | 39 | 0 | 1 | 97.5% | 90% |
| *17/*17 | 11 | 11 | 0 | 0 | 100.0% | 80% |
| *2/*3 | 6 | 6 | 0 | 0 | 100.0% | 69% |
| *2/*17 | 15 | 15 | 0 | 0 | 100.0% | 85% |
| *3/*17 | 1 | 1 | 0 | 0 | 100.0% | 27% |
| TOTAL | 325 | 321 | 0 | 4 | 98.8% | 97% |

4 Genotype by bi-directional sequencing; *1/*1 samples are wild-type for *2, *3, and *17.

" Gellowye by ordinestional soquenting" "1" " oaily of all three genotypes ("2, "3, *17) had to be correct.

Table 3b – Method Comparison – SECOND PASS

| Genotypea | #
Samples
tested | #
Correct
Callsb | #
Incorrect
calls | # No calls | %
Correct
calls | 95% One-
sided
confidence
lower limit |
|-----------|------------------------|------------------------|-------------------------|------------|-----------------------|------------------------------------------------|
| *1/*1 | 130 | 130 | 0 | 0 | 100.0% | 98% |
| *1/*2 | 95 | 95 | 0 | 0 | 100.0% | 97% |
| *2/*2 | 19 | 19 | 0 | 0 | 100.0% | 88% |
| *1/*3 | 7 | 7 | 0 | 0 | 100.0% | 72% |
| *3/*3 | 1 | 1 | 0 | 0 | 100.0% | 27% |
| *1/*17 | 40 | 40 | 0 | 0 | 100.0% | 94% |
| *17/*17 | 11 | 11 | 0 | 0 | 100.0% | 80% |
| *2/*3 | 6 | 6 | 0 | 0 | 100.0% | 69% |
| *2/*17 | 15 | 15 | 0 | 0 | 100.0% | 85% |
| *3/*17 | 1 | 1 | 0 | 0 | 100.0% | 27% |
| TOTAL | 325 | 325 | 0 | 0 | 100.0% | 99% |

Genotype by bi-directional sequencing; *1/*1 samples are wild-type for *2, *3, and *17,

" Genotype by bronnethonal sequentling, "17" valiptor of all three genotypes (*2, *3, *17) had to be correct.

For the Transport System, the first pass results were 109/110, 105/106,107/109 for the immediate, 10 ron the Transport Oyotom the points, respectively. All results were 100% on the second pass.

8

Tratel seber Machy & epocal solidition - FIRST PASS

Buccal swab samples were collected from *1/*17, *2/*3, *1/*1, *1/*3, *2/*17, *2/*2, and *1/*2 individuals (one individual per genotype) across three sites. Genotypes of the eight individuals were confirmed by bi-directional sequencing. Two operators were employed at each site, and tests were performed across five non-consecutive days. Typically, operators were laboratory technicians who had no previous experience with swabbing. At one site, two of the operators did not work in the medical or provide oxperience ware two sessions per day (AM and PM), and each session was split into two subsessions. In each sub-session, each of the eight individuals was tested once by Operator 1 and once by Operator 2. If the result of the first test for a particular individual was a No call, the test was repeated (second pass). Results of the inter-laboratory reproducibility study are presented in Tables 4a and 4b.

Sample Type*	Site	# samples tested	# no calls	# Incorrect calls	# correct calls	% correct call rate	95% Confidence Limit
1/1	1	40	0	0	40	100.0%	94%
	3	40	1	0	39	97.5%	90%
	4	40	0	1*	39	97.5%	90%
	Total	120	1	1	118	98.3%	95%
1/2	1	40	0	0	40	100.0%	94%
	3	40	0	0	40	100.0%	94%
	4	40	0	0	40	100.0%	94%
	Total	120	0	0	120	100.0%	98%
2/2	1	40	2	0	38	95.0%	86%
	3	40	0	0	40	100.0%	94%
	4	40	0	0	40	100.0%	94%
	Total	120	2	0	118	98.3%	95%
1/3	1	40	1	0	39	97.5%	90%
	3	40	1	0	39	97.5%	90%
	4	40	0	0	40	100.0%	94%
	Total	120	2	0	118	98.3%	95%
2/3	1	40	0	0	40	100.0%	94%
	3	40	0	0	40	100.0%	94%
	4	40	3	0	37	92.5%	83%
	Total	120	3	0	117	97.5%	94%
1/17	1	40	0	0	40	100.0%	94%
	3	40	0	0	40	100.0%	94%
	4	40	0	0	40	100.0%	94%
	Total	120	0	0	120	100.0%	98%
17/17	1	40	0	0	40	100.0%	94%
	3	40	1	0	39	97.5%	90%
	4	40	1	0	39	97.5%	90%
	Total	120	2	0	118	98.3%	95%
2/17	1	40	0	0	40	100.0%	94%
	3	40	0	0	40	100.0%	94%
	4	40	0	0	40	100.0%	94%
	Total	120	0	0	120	100.0%	98%
TOTAL	1	320	3	0	317	99.1%	98%
	3	320	3	0	317	99.1%	98%
	4	320	4	1	315	98.4%	97%
	Total	960	10	1	949	98.9%	98%

Table 4a - Inter-Laboratory Reproducibility - FIRST PASS

4 Genotype by bi-directional sequencing; *1/*1 samples are wild-type for *2, *3, and *17.

" Galleryo by a sample to be deemed a correct call, results of all three genotypes (*2, *3, *17) had to be correct.

" The root cause of the incorrect call could not conclusively be determined, but it was not due to bubbles in the reaction tube.

9

| Sample
Typea | Site | # samples
tested | # no
calls | #
incorrect
calls | #
correct
callsb | % correct call
rate | 95%
Confidence
Limit |
|-----------------|-------|---------------------|---------------|-------------------------|------------------------|------------------------|----------------------------|
| *1/1 | 1 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 3 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 4 | 40 | 0 | 1 | 39 | 97.5% | 90% |
| | Total | 120 | 0 | 1 | 119 | 99.2% | 96% |
| *1/*2 | 1 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 3 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 4 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | Total | 120 | 0 | 0 | 120 | 100.0% | 98% |
| *2/*2 | 1 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 3 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 4 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | Total | 120 | 0 | 0 | 120 | 100.0% | 98% |
| *1/*3 | 1 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 3 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 4 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | Total | 120 | 0 | 0 | 120 | 100.0% | 98% |
| *2/*3 | 1 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 3 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 4 | 40 | 1 | 0 | 39 | 97.5% | 90% |
| | Total | 120 | 1 | 0 | 119 | 99.2% | 96% |
| *1/*17 | 1 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 3 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 4 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | Total | 120 | 0 | 0 | 120 | 100.0% | 98% |
| *17/*17 | 1 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 3 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 4 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | Total | 120 | 0 | 0 | 120 | 100.0% | 98% |
| *2/*17 | 1 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 3 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | 4 | 40 | 0 | 0 | 40 | 100.0% | 94% |
| | Total | 120 | 0 | 0 | 120 | 100.0% | 98% |
| TOTAL | 1 | 320 | 0 | 0 | 320 | 100.0% | 99% |
| | 3 | 320 | 0 | 0 | 320 | 100.0% | 99% |
| | 4 | 320 | 1 | 1 | 318 | 99.4% | 99% |
| | Total | 960 | 1 | 1 | 958 | 99.8% | 99% |

ª Genotype by bi-directional sequencing; *1/*1 samples are wild-type for *2, *3, and *17.

Genotype by brunectional bequeneing, " } " call, results of all three genotypes ("2, * 3, * 1 7) had to be correct.

*The rot cause of the incorrect call could not conclusively be determined, but it was not due to bubbles in the reaction tube.

Overall, a total of 960 tests were performed—10 second pass tests were performed due to No calls on the first pass test, and all but 1 were recovered.

Overall, after second pass testing of No call genotype results, the Spartan RX CYP2C19 System Overall, aller Scoonia pass toeing of No San Gerry Jre-sided lower confidence limit of 99%.

10

Relateetblocklister-llato@ephong.com/lity - SECOND PASS

Lot-to-lot reproducibility was assessed using three independent lots of each reagent type labeled as 1,2 Eot to Toproducibility had account the Site 1 Inter-laboratory Reproducibility study.

On the first pass, 3 samples produced No call results. After the second pass, all of these samples On the first pass, o samples produced the cesults indicate that different reagent lots perform equivalently.

First and second pass results for the Reagent Lot-to-Lot Reproducibility study are presented in Tables 5a and 5b, respectively.

| Reagent Lot | Genotype" | # Samples
tested | # Correct
callsb | #
incorrect
calls | # No calls | % Correct calls
(95% one-sided
confidence lower
limit) |
|-------------|-----------|---------------------|---------------------|-------------------------|------------|-----------------------------------------------------------------|
| | *2/*17 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *1/*2 | 14 | 14 | 0 | 0 | 100% (84%) |
| | *1/*17 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *17/*17 | 13 | 13 | 0 | 0 | 100% (83%) |
| Lot 1 | *1/*1 | 14 | 14 | 0 | 0 | 100% (84%) |
| | *2/*3 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *2/*2 | 13 | 11 | 0 | 2 | 85% (63%) |
| | *1/*3 | 14 | 13 | 0 | 1 | 93% (73%) |
| | Total | 107 | 104 | 0 | 3 | 97% (93%) |
| | *2/*17 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *1/*2 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *1/*17 | 14 | 14 | 0 | 0 | 100% (84%) |
| | *17/*17 | 13 | 13 | 0 | 0 | 100% (83%) |
| Lot 2 | *1/*1 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *2/*3 | 14 | 14 | 0 | 0 | 100% (84%) |
| | *2/*2 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *1/*3 | 13 | 13 | 0 | 0 | 100% (83%) |
| | Total | 106 | 106 | 0 | 0 | 100% (98%) |
| | *2/*17 | 14 | 14 | 0 | 0 | 100% (84%) |
| | *1/*2 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *1/*17 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *17/*17 | 14 | 14 | 0 | 0 | 100% (84%) |
| Lot 3 | *1/*1 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *2/*3 | 13 | 13 | 0 | 0 | 100% (83%) |
| | *2/*2 | 14 | 14 | 0 | 0 | 100% (84%) |
| | *1/*3 | 13 | 13 | 0 | 0 | 100% (83%) |
| | Total | 107 | 107 | 0 | 0 | 100% (98%) |

Table 5a – Reagent Lot-to-Lot Reproducibility – FIRST PASS

4 Genotype by bi-directional sequencing; *1/*1 samples are wild-type for *2, *3, and *17,

Genotype by bledited be deemed a correct call, results of all three genotypes (*2, *3, *17) had to be correct.

11

Reagent Lot	Genotypea	# Samples tested	# Correct calls	% Correct calls (95% one-sided confidence lower limit)
Lot 1	2/17	13	13	100% (83%)
	1/2	14	14	100% (84%)
	1/17	13	13	100% (83%)
	17/17	13	13	100% (83%)
	1/1	14	14	100% (84%)
	2/3	13	13	100% (83%)
	2/2	13	13	100% (83%)
	1/3	14	14	100% (84%)
	Total	107	107	100% (98%)
Lot 2	2/17	13	13	100% (83%)
	1/2	13	13	100% (83%)
	1/17	14	14	100% (84%)
	17/17	13	13	100% (83%)
	1/1	13	13	100% (83%)
	2/3	14	14	100% (84%)
	2/2	13	13	100% (83%)
	1/3	13	13	100% (83%)
	Total	106	106	100% (98%)
Lot 3	2/17	14	14	100% (84%)
	1/2	13	13	100% (83%)
	1/17	13	13	100% (83%)
	17/17	14	14	100% (84%)
	1/1	13	13	100% (83%)
	2/3	13	13	100% (83%)
	2/2	14	14	100% (84%)
	1/3	13	13	100% (83%)
	Total	107	107	100% (98%)

Table 5b – Reagent Lot-to-Lot Reproducibility – SECOND PASS

*Genotype by bi-directional sequencing; *1/*1 samples are wild-type for 2, 3, and 17.

Genotype by bi-directional sequencing; *1,71 samples are wild-type for *2, *3, and *17.
In order for a sample to be deemed a correct call, results of all three genotypes

:

·

12

Exogenous and Endogenous Interfering Substances

Interference from exogenous and endogenous interfering substances was evaluated using buccal swab samples collected from *1/*1, *2/*17, *17/*17, and *2/*3 individuals. Genotypes of all individuals were confirmed by bi-directional sequencing prior to initiation of the study.

To test the impact of exogenous substances, buccal swab samples were collected from individuals after exposure to the substance. The individuals rinsed with water (as per the Instructions for Use for the Spartan RX CYP2C19 System) before swab collection.

Direct exposure of individuals to endogenous substances was not possible. Therefore, these substances were added directly to the reagent tube immediately prior to insertion of the buccal swab sample. Note that the Instructions for Use require the patient to rinse his or her mouth with water prior to collection of the buccal swab sample. The purpose of the water rinse is to remove any contaminating endogenous materials such as blood or blood components. So although certain endogenous substances will interfere with performance of the Spartan RX CYP2C19 System, this risk is mitigated by the water rinse.

The following exogenous and endogenous substances were tested:

Antiseptic mouthwash	–	20 ml - Rinse around mouth for 30 s
Toothpaste	-	3/4" Strip - Brush teeth for 2 min, spit
Baking soda solution	ー	30 ml (0.1 g /ml) – Rinse around mouth for 10 s
Cough syrup	।	30 ml - Rinse around mouth for 10 s
Cranberry juice	-	30 ml – Rinse around mouth for 10 s
Salt water	l	30 ml (0.01 g/ml) - Rinse around mouth for 10 s
Sugar water	-	30 ml (0.01 g/ml) -- Rinse around mouth for 10 s
Meat	–	15 g – Chew for 10 s
Chewing gum	-	1 standard piece - Chew for 1 min
Hard candy	–	1 standard piece - Suck until fully dissolved
Tobacco smoking	-	1 cigar - 5 puffs
Denture paste	I	3 strips – Apply strips to roof of mouth, leave for 5 min,
		remove
Human Oral Bacteria		Approximately 9 x 104 cells (in addition to normal oral flora)
Whole Blood	-	3.5 µl of 0.5% blood (diluted in saliva)

A total of 16 samples were tested for each exogenous and endogenous interfering substance (n=4 per genotype tested). If the result of the first test for a particular individual was a No call, the test was repeated (second pass).

The results of the Exogenous and Endogenous Interfering Substances study indicate that substances commonly introduced into the oral environment do not affect performance of the Spartan RX CYP2C19 System. Nevertheless, proper rinsing and swabbing techniques must be followed to minimize the rate of No calls associated with inhibiting substances.

Results of first and second pass tests performed during the Exogenous and Endogenous Interfering Substances study are summarized in Tables 6a and 6b, respectively.

13

Genotype	Substance	# Samples tested	# Correct calls	# No calls	% Correct calls	95% one-sided confidence lower limit
Combined genotype results	Mouthwash	16	15	1	93.8%	76%
	Toothpaste	16	5	11	31.3%	16%
	Baking soda	16	14	2	87.5%	68%
	Cough syrup	16	16	0	100.0%	86%
	Cranberry juice	16	16	0	100.0%	86%
	NaCl solution	16	16	0	100.0%	86%
	Sugar solution	16	16	0	100.0%	86%
	Meat (horse)	16	16	0	100.0%	86%
	Chewing gum	16	14	2	87.5%	68%
	Hard candy	16	16	0	100.0%	86%
	Tobacco (cigar)	16	15	1	93.8%	76%
	Denture paste	16	16	0	100.0%	86%
	Bacteria	16	15	1	93.8%	76%
	Whole blood	16	15	1	93.8%	76%
	Total	224	205	19	91.5%	88%

4 In order for a sample to be deemed a correct call, results of all three genotypes (*2, *3, *17) had to be correct.

Table 6b - Exogenous and Endogenous Interfering Substances - SECOND PASS
--------------------------------------------------------------------------	--	--	--

| Genotype | Substance | #
Samples
tested | # Correct
callsa | #
incorrect
calls | # No
calls | % Correct
calls | 95% one-
sided
confidence
lower limit |
|---------------------------------|-----------------|------------------------|---------------------|-------------------------|---------------|--------------------|------------------------------------------------|
| | Mouthwash | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Toothpaste | 16 | 15 | 0 | b | 93.75% | 76% |
| | Baking soda | 16 | 16 | 0 | 0 | 100.00% | 86% |
| Combined
genotype
results | Cough syrup | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Cranberry juice | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | NaCl solution | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Sugar solution | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Meat (horse) | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Chewing gum | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Hard candy | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Tobacco (cigar) | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Denture paste | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Bacteria | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Whole blood | 16 | 16 | 0 | 0 | 100.00% | 86% |
| | Total | 224 | 223 | 0 | 1 | 99.55% | 98% |

ª In order for a sample to be deemed a correct call, results of all three genotypes (*2, *3, * 17) had to be correct.

in over for a damps to bo been esignificantly different. For the tist pass, three mointable did not ninse out all of " First and second pass results in tourine and more one all all the took and the tooking the the the neeming the broe the toothpaste before swabing. For the Secure pass, all for the world be and are are are are and and and least three minutes before swabbing.

14

Image /page/14/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized emblem resembling a caduceus, with three wavy lines emanating from a central point. The emblem is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.

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

August 12, 2013

Spartan Bioscience Inc. c/o Lorry Huffman c/o Myraqua, Inc. 3 Lagoon Drive, Ste 280 REDWOOD SHORES CA 94065

Re: K123891

Trade/Device Name: Spartan RX™ CYP2C19 System Regulation Number: 21 CFR 862.3360 Regulation Name: Drug metabolizing enzyme genotyping system Regulatory Class: II Product Code: NTI, NSU Dated: June 28, 2013 Received: July 3, 2013

Dear Ms. Huffman:

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 Part 801); 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.

15

Page 2- Ms. Huffman

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Small Manufacturers, International and Consumer Assistance 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.

Sincerely yours,

Carol C. Benson -S 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

16

Indications for Use Form

510(k) Number (if known): _ K123891

Device Name: Spartan RX CYP2C19 System

Indications for Use:

Assay - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Assay will be run on the Spartan RX Platform from the buccal sample collected with a buccal swab. The Spartan RX CYP2C19 Assay is not indicated to be used to predict drug response or non-response.

Platform - The Spartan RX CYP2C19 System is indicated for use as an aid to clinicians in determining therapeutic strategies for therapeutics that are metabolized by the Cytochrome P450 2C19 gene product, and that are specifically affected by the *2, *3, and *17 alleles. The Spartan RX CYP2C19 Platform will be used to run the Spartan RX CYP2C19 Assay.

Prescription Use	X
(Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use
(21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Ruth A. Cheslier -S

Division Sign-Off Office of In Vitro Diagnostics and Radiological Health

K123891 510(K)

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