Predicate Devices

INFINITI Warfarin Assay (K073014), AmpliChip CYP450 Microarray (K043576)

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard in vitro diagnostic assay utilizing microarray technology and automated processes for genotyping. There is no mention of AI or ML in the device description, intended use, or performance studies. The analysis and results are presented as genotype calls based on signal detection and analysis, which is typical for this type of technology and does not inherently involve AI/ML.

Therapeutic

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

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states, "The INFINITI CYP2C19 Assay is an in vitro diagnostic test for the identification of a patient's CYP450 2C19 genotype... The INFINITI CYP2C19 Assay is indicated for use as an aid to clinicians in determining therapeutic strategy..." and the "Device Description" section later reiterates, "The INFINITI CYP2C19 Assay is an in vitro diagnostic device".

SaMD (Software as a Medical Device)

No

The device description explicitly states it is an in vitro diagnostic device that utilizes proprietary film-based microarray technology, reagent management, and is comprised of physical components like the BioFilmChipTM Microarray, Intellipac Reagent Module, and PCR Amplification Mix. It also requires the use of the AutoGenomics INFINITI Analyzer, a hardware component.

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 INFINITI CYP2C19 Assay is an in vitro diagnostic test..." and describes its use for identifying a patient's genotype from a biological sample (whole blood) to aid clinicians in determining therapeutic strategy. This aligns directly with the definition of an in vitro diagnostic device, which is used to examine specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of a disease or condition.
Device Description: The description details a device that processes biological samples (DNA from whole blood) using laboratory techniques (PCR amplification, hybridization, scanning) to produce a result (genotype calls). This is characteristic of an IVD.
Intended User/Care Setting: The device is intended for use in "clinical laboratories upon prescription by the attending physician," which is a typical setting for IVD testing.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for 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 CYP2C19 Assay is a qualitative assay for use in clinical laboratories upon prescription by the attending physician.

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 non-response.

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

NTI, NSU

Device Description

The INFINITI CYP2C19 Assay is an in vitro diagnostic device which utilizes proprietary film-based microarray technology combined with process automation, reagent management, and software technology for the detection and genotyping of the 2C19 *2, *3, and *17 mutations in genomic deoxyribonucleic acid (DNA) obtained from EDTA anticoagulated whole blood samples.

The INFINITI CYP2C19 Assay is comprised of the BioFilmChipTM Microarray, the Intellipac Reagent Module and the PCR Amplification Mix. The INFINITI CYP2C19 Assay should be run using the AutoGenomics INFINITI Analyzer.

The BioFilmChip Microarray consists of a polyester film coated with proprietary multi-layer components designed for DNA analysis. The layers have been designed to provide a versatile surface to enhance test performance. There can be up to 240 spots per microarray with each spot representing a different allele. The microarrays are designed to be assay specific.

The Intellipac Reagent Module contains up four reservoirs that house the test reagents and has an integrated memory chip. Information on the reagent such as lot number, expiration date and remaining tests, are archived in the memory.

The PCR Amplification Mix consists of the reagents needed for the PCR amplification step of the assay.

The INFINITI CYP2C19 Assay is based on the following processes: (a) DNA extraction (b) PCR amplification of purified DNA from human genomic DNA (c) Labeling of the amplified product (allele specific primer extension) (d) Hybridization of the labeled amplified product to a microarray by signature Tag/Capture probe hybridization under isothermal conditions. (e) Scanning of the microarray (f) Signal detection and analysis Steps (c) through (f) are automated by the INFINITI Analyzer. The INFINITI Analyzer automates the 2C19 assay and integrates all the discrete processes of sample (PCR amplicon) handling, reagent management, hybridization, and results. The assays are processed automatically and read by the built-in confocal microscope. Results are analyzed and presented as genotype calls.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

clinical laboratories

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

Limit of Detection (analytical sensitivity)
The analytical sensitivity (Limit of Detection) of the INFINITI CYP2C19 Assay was assessed by analysis of whole blood samples at serial dilutions representing 500ng, 100ng, 100ng, 50ng, 20ng, 10ng and 5ng DNA input (per test) to determine the lowest level of genomic DNA (ng input per test) that would give a >= 90% correct call rate of the allele with no incorrect calls.
The following whole blood samples were used in the LOD studies: * 1/*1, * 1/*17, * 1/*17, *2/*2 and *2/*17. Sample genotype was determined by bi-directional sequencing.
Two extraction methods were used in the studies: Qiagen Q1Aamp DNA Blood Kit and the PSS Magtration System. The concentration and A260/A280 were determined by spectrophotometry for the extracted DNA.
A total of 1,560 tests were completed for the LOD studies.

Percent Agreement vs. Bi-directional Sequencing
The INFINITI CYP2C19 Assay was compared to bi-directional sequencing as the comparator method. Three sites were used for the comparison studies. Each site tested its own patient samples with the INFINITI CYP2C19 Assay. Patient samples were de-identified to protect patient's identity.
A total of 317 samples were tested.

Assay Inter-Laboratory Reproducibility
A three-site study was conducted to demonstrate the reproducibility of the INFINITI CYP2C19 Assay. The study involved three identical lots of the INFINITI CYP2C19 Assay, four operators, and four instruments (one site ran two sets of reproducibility studies, each with a different operator and instrument).
The sites ran identical samples comprised of 12 whole blood samples. The sites were blinded to sample identity. At each site, each sample was run in duplicate per day/operator for five non-consecutive days. A total of 430 tests were run.
Additional reproducibility studies were conducted at the same three sites to demonstrate the reproducibility of the INFINITI CYP2C19 Assay for additional samples including *2/*3. The study involved three lots of the INFINITI CYP2C19 Assay. The sites ran identical samples comprised of six (6) genomic whole blood samples. The sites were blinded to sample identity. At each sample was run in triplicate per day/operator for five nonconsecutive days.
A total of 255 tests were completed.

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

Analytical Specificity
Studies related to specificity were conducted during assay development. PCR primer specificity was determined by amplicon size on a gel and sequencing the amplicon. ASP primer specificity was determined by the correct calls made by the assay using known genomic samples. Capture probe specificity was determined by hybridizing different oligos and demonstrating that correct oligo hybridizes to the known spot.

Limit of Detection (analytical sensitivity)
The analytical sensitivity (Limit of Detection) of the INFINITI CYP2C19 Assay was assessed by analysis of whole blood samples at serial dilutions representing 500ng, 100ng, 100ng, 50ng, 20ng, 10ng and 5ng DNA input (per test).
A total of 1,560 tests were completed. A >= 90% correct call rate with no incorrect calls for the allele was obtained at DNA input levels from 400ng/test to 5ng/test. There was one incorrect call at the 5ng DNA input level. The incorrect call was probably due to the low DNA concentration.
The lowest detectable level for the INFINITI CYP2C19 Assay is 20ng DNA per test.

Percent Agreement vs. Bi-directional Sequencing
The INFINITI CYP2C19 Assay was compared to bi-directional sequencing as the comparator method. Three sites were used for the comparison studies. A total of 317 samples were tested.
There were no incorrect calls. Six samples (1.9%) had to be repeated because of "no call" due to NTCE is reported when the quality or quantity of the DNA in the sample/PCR product is poor. All six no calls gave correct calls upon the repeat for a 100% agreement of the INFINITI CYP2C19 Assay with bi-directional sequencing. The repeat test was done on the same extracted DNA. Only one repeat was done for each sample.
Overall agreement was 98.1%, with a 95% One-sided Confidence Lower Limit of 96.4%.

Assay Inter-Laboratory Reproducibility
A three-site study was conducted to demonstrate the reproducibility of the INFINITI CYP2C19 Assay. A total of 430 tests were run. Of the 430 samples assayed, 14 samples (3.3%) had to be repeated due to "No Calls". The samples were repeated using the same extracted DNA. These NTCE errors might have been caused by temperature gradient during PCPc.imrooner sealing of the PCR tubes, or operator pipetting error. The genotype calls from the repeat assays were 100% correct, There was one incorrect call (*1/*2 instead of *2/*2). The root cause of the incorrect call was not definitively determined.
Additional reproducibility studies were conducted at the same three sites. A total of 255 tests were completed. Overall correct call rate for the first time run was 97.6%. There were no incorrect calls. There were six no calls.
Summary of combined reproducibility studies (685 replicates):
Correct Call Rate: 96.9%, 95% One-sided Confidence Lower Limit: 95.6%
Total No Calls: 20
Total Incorrect Calls: 1

Interference
Interference from potential interfering substances was evaluated using eight (8) whole blood samples. The potential interfering substances were added separately to the whole blood sample prior to DNA extraction and testing with the INFINITI CYP2C19 Assay. Genotype results were compared to those obtained from non-spiked samples. Sample genotype was verified by bi-directional DNA sequencing. The interference studies demonstrated that the INFINITI CYP2C19 Assay performance was not affected by the addition of Bilirubin (conjugated, 60mg/dl), Bilirubin (unconjugated, 60mg/dl), Triglycerides (Intralipid, 3000mg/dl), and Human albumin (6g/dl). No studies were conducted with oral anti-coagulants, and no claims are being made.

Sample Carry-Over
No sample carry-over was detected when 300ng of a positive sample was followed by 10ng of a second positive sample, and when 300ng of a positive sample was followed by a "No Template Control" or water. All genotype calls were 100% correct.

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

Limit of Detection: The lowest detectable level for the INFINITI CYP2C19 Assay is 20ng DNA per test.
Percent Agreement vs. Bi-directional Sequencing (Overall): Agreement 98.1%, 95% One-sided Confidence Lower Limit 96.4%.
Assay Inter-Laboratory Reproducibility (Combined): Correct Call Rate 96.9%, 95% One-sided Confidence Lower Limit 95.6%.

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 Warfarin Assay (K073014), AmpliChip CYP450 Microarray (K043576)

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

| Submitted By | AutoGenomics, Inc.
2980 Scott Street
Vista, CA 92081, USA
Telephone: (760) 477-2248
FAX: (760) 477-2251

Contact: Evelyn Lopez
Vice President, Regulatory Affairs

Date Prepared: October 22, 2010 | K101683
OCT 25 2010 |
|----------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------|
| Device Name | Trade or Proprietary Name: | INFINITI CYP2C19 Assay |
| | Common or Usual Name: | Cytochrome P450 CYP2C19 Test |
| Regulations and
Product Codes | Regulations: | 21CFR§862.3360 Drug Metabolizing Enzyme Genotyping Systems
21CFR§862.2570 Instrumentation for Clinical Multiplex Test Systems |
| | Classification: | Class II |
| | Product Codes: | NTI Drug Metabolizing Enzyme Genotyping System
NSU Instrumentation for Clinical Multiplex Test Systems |
| Predicate Device | (a) INFINITI Warfarin Assay (K073014)
(b) AmpliChip CYP450 Microarray (K043576) | |
| Device Description | The INFINITI CYP2C19 Assay is an in vitro diagnostic device which utilizes proprietary
film-based microarray technology combined with process automation, reagent
management, and software technology for the detection and genotyping of the 2C19 *2,
*3, and *17 mutations in genomic deoxyribonucleic acid (DNA) obtained from EDTA-
anticoagulated whole blood samples. | |
| | The INFINITI CYP2C19 Assay is comprised of the BioFilmChipTM Microarray, the
Intellipac Reagent Module and the PCR Amplification Mix. The INFINITI CYP2C19
Assay should be run using the AutoGenomics INFINITI Analyzer. | |
| | The BioFilmChip Microarray consists of a polyester film coated with proprietary multi-
layer components designed for DNA analysis. The layers have been designed to provide
a versatile surface to enhance test performance. There can be up to 240 spots per
microarray with each spot representing a different allele. The microarrays are designed to
be assay specific. | |
| | The Intellipac Reagent Module contains up four reservoirs that house the test reagents and
has an integrated memory chip. Information on the reagent such as lot number, expiration
date and remaining tests, are archived in the memory. | |
| | The PCR Amplification Mix consists of the reagents needed for the PCR amplification
step of the assay. | |

.

·

.

1

The INFINITI CYP2C19 Assay is based on the following processes: (a) DNA extraction (b) PCR amplification of purified DNA from human genomic DNA (c) Labeling of the amplified product (allele specific primer extension) (d) Hybridization of the labeled amplified product to a microarray by signature Tag/Capture probe hybridization under isothermal conditions. (e) Scanning of the microarray (f) Signal detection and analysis Steps (c) through (f) are automated by the INFINITI Analyzer. The INFINITI Analyzer automates the 2C19 assay and integrates all the discrete processes of sample (PCR amplicon) handling, reagent management, hybridization, and results The assays are processed automatically and read by the built-in confocal analysis. microscope. Results are analyzed and presented as genotype calls. 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 CYP2C19 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. Substantial Table 1a and Table 1b provide a comparison of the INFINITI CYP2C19 Assay to the Equivalence predicate devices. The comparison demonstrates that the INFINITI CYP2C19 Assay is substantially equivalent to the predicate devices.

	Predicate	Subject Device
Characteristics	INFINITI Warfarin Assay
(K073014)	INFINITI CYP2C19 Assay
	Similarities
DNA sequence	Detects specific DNA sequences through recognition of DNA targets	Same
Technology	Microarray-based genotyping test for simultaneous detection (multiplex system) of DNA sequences	Same
Specimen Type	Purified DNA from EDTA-anticoagulated whole blood sample	Same
Reaction Conditions	Utilizes thermal cycling
Utilizes target DNA amplification
Reactions occur on a single biofilm microarray chip	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
Instrumentation	INFINITI Analyzer	Same
	Differences
Target Genes	CYP4502C9 and VKORC1	CYP4502C19

Table ta

2

Characteristics	Predicate	Subject Device
	AmpliChip CYP450 Microarray (K043576)	INFINITI CYP2C19 Assay
	Similarities
Indication for use	As an aid in determining therapeutic strategy
and treatment dose for therapeutics that are
metabolized by the CYP450 2C19 gene
product.	As an aid in determining therapeutic strategy
for therapeutics that are metabolized by the
CYP450 2C19 gene product. Not intended to
predict drug response or non-response
DNA sequence	Detects specific DNA sequences through
recognition of DNA targets	Same
Specimen Type	Purified DNA from EDTA-anticoagulated
whole blood sample	Same
Technology	Microarray-based genotyping test for
simultaneous detection (multiplex system) of
DNA sequences	Same
Reaction
Conditions	Utilizes thermal cycling Utilizes target DNA amplification Reactions occur on a single biofilm microarray chip	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	CYP450 2C19	Same
	Differences
Target Gene
Mutations	CYP450 2C19 2 and 3	CYP450 2C19 2, 3, and *17

Performance The following are performance characteristics of the INFINITI CYP2C19 Assay:

Analytical Specificity

Studies related to specificity were conducted during assay development. PCR primer specificity was determined by amplicon size on a gel and sequencing the amplicon. ASP primer specificity was determined by the correct calls made by the assay using known genomic samples. Capture probe specificity was determined by hybridizing different oligos and demonstrating that correct oligo hybridizes to the known spot.

Limit of Detection (analytical sensitivity)

The analytical sensitivity (Limit of Detection) of the INFINITI CYP2C19 Assay was assessed by analysis of whole blood samples at serial dilutions representing 500ng, 100ng, 100ng, 50ng, 20ng, 10ng and 5ng DNA input (per test) to determine the lowest level of genomic DNA (ng input per test) that would give a ≥ 90% correct call rate of the allele with no incorrect calls.

The following whole blood samples were used in the LOD studies: * 1/*1, * 1/*17, * 1/*17, *2/*2 and *2/*17. Sample genotype was determined by bi-directional sequencing.

Two extraction methods were used in the studies: Qiagen Q1Aamp DNA Blood Kit and the PSS Magtration System. The concentration and A260/A280 were determined by spectrophotometry for the extracted DNA.

A total of 1,560 tests were completed for the LOD studies. A ≥ 90% correct call rate with no incorrect calls for the allele was obtained at DNA input levels from 400ng/test to 5ng/test. There was one incorrect call at the 5ng DNA input level. The incorrect call was probably due to the low DNA concentration, therefore, we are not recommending DNA input level at this low concentration.

3

The lowest detectable level for the INFINITI CYP2C19 Assay is 20ng DNA per test. This is less than one-half (1/2) the recommended DNA input level of 50ng/test, and four times the level at which an incorrect call was made by the assay. We believe that establishing the lowest detectable level at 200g DNA/test is conservative and should by and an incorrect call.

Table 2 provides a summary of the LOD studies for the INFINITI CYP2C19 Assay.

	ngDNA : }				% correct »	:95% One-sideo
Sample	input per	Replicates		Correct Incorrect	. calls 15	Confidence
ID	test	tested ·	calls	calls	time.run	Lower Limit
		માં, તુ

1.4 2.4 | | 11:21:34 : 1 | | - الوقوب الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع الموقع المو | : ・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・・ |
| | | 200 | 40 | 34 | 0 | б | 85.0% | 72.7% |
| | AG44 | 400 | 40 | 38 | 0 | 2 | 95.0% | 87.0% |
| | AG105 | 200 | 40 | 38 | 0 | 2 | 95.0% | 87.0% |
| | AG208 | 100 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| * 1/* I | AG209 | રેપ | 40 | ਤੇ ਰੇ | 0 | l | 97.5% | 91.4% |
| | AG211 | 20 | 40 | 39 | 0 | l | 97.5% | 91.4% |
| | AG219 | 10 | 40 | 38 | 0 | 2 | 95.0% | 87.0% |
| | | 5 | 40 | 39 | 0 | 1 | 97.5% | 91.4% |
| | Total | | ~320
: | 305
. . | 0 - | । ਤ
t | 95.3% | - 92.8% - - 92.8% - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - |
| | | 500 | 20 | . ਉ | 0 | l | 95.0% | 82.9% |
| | | 400 | 20 | 20 | 0 | 0 | 100% | 97.5% |
| | AG81 | 200 | 20 | 20 | 0 | 0 | 100% | 97.5% |
| | AG197 | 100 | 20 | 20 | 0 | 0 | 100% | 97.5% |
| *1/*2 | AG210
AG223 | રુ | 40 | 37 | 0 | 3 | 92.5% | 83.1% |
| | | 20 | 40 | 36 | 0 | 4 | 90.0% | 79.5% |
| | | 10 | 40 | 38 | 0 | 2 | 95.0% | 87.0% |
| | | 5 | 40 | ਤੇ ਰੇ | 0 | 1 | 97.5% | 91.4% |
| | Total | | 240" | : 229 : | 0 - 0 - 1 - | 11 | 95.4%
ﺮ ﺍﻟﻤﺮﺍﺟﻊ
【】 | 92.6% |
| | AG82 | 200 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 400 | 40 | 39 | 0 | l | 97.5% | 91.4% |
| | | 200 | 40 | 37 | 0 | 3 | 92.5% | 83.1% |
| | AG199 | 100 | 40 | 39 | 0 | l | 97.5% | 91.4% |
| *2/*2 | AG214 | રી | 40 | 37 | 0 | 3 | 92.5% | 83.1% |
| | AG233 | 20 | 40 | 38 | 0 | 2 | 95.0% | 87.0% |
| | | 10 | 40 | 37 | 0 | 3 | 92.5% | 83.1% |
| | | 5 | 40 | 37 | 0 | 3 | 92.5% | 83.1% |
| | Total
r ¿ , | | - 320 | 4 . 304 | 200000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000 | . 16 | 95.0% - 2 | 92.5% |
| *1/*3 | | 500 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 400 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 200 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | AG152
AG162 | 100 | 40 | 39 | 0 | l | 97.5% | 91.4% |
| | | રુભ | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 20 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 10 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 5 | 40 | 38 | 1 | 1 | 95.0% | 87.0% |
| | Total | | 320 : --
、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、、 | 317 - 317 - | 1945 1 1 2 2 2 2 2 2 | | | 199.1% = 1 + 97.9% |
| Genotype | Sample ID | ngDNA input per test | Replicates tested | Correct calls | Incorrect calls | No calls | % correct calls 1st time run | 95% One-sided Confidence Lower Limit |
| *1/*17 | AG74 | 500 | 40 | 36 | 0 | 4 | 90.0% | 79.5% |
| | AG94 | 400 | 40 | 38 | 0 | 2 | 95.0% | 87.0% |
| | AG180 | 200 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | AG235 | 100 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 50 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 20 | 40 | 38 | 0 | 2 | 95.0% | 87.0% |
| | | 10 | 40 | 40 | 0 | 0 | 100% | 98.8% |
| | | 5 | 40 | 39 | 0 | 1 | 97.5% | 91.4% |
| Total | | 320 | 311 | 0 | 9 | 97.2% | 95.2% | Total |
| *2/*17 | AG191 | 100 | 20 | 20 | 0 | 0 | 100% | 97.5% |
| | AG195 | 5 | 20 | 20 | 0 | 0 | 100% | 97.5% |
| Total | | | 40 | 40 | 0 | 0 | 100% | 98.8% |

Table 2 Limit of Detection

4

a determined by bi-directional sequencing

Percent Agreement vs. Bi-directional Sequencing

The INFINITI CYP2C19 Assay was compared to bi-directional sequencing as the comparator method. Three sites were used for the comparison studies. Each site tested its own patient samples with the INFINITI CYP2C19 Assay. Patient samples were de-identified to protect patient's identity.

. A total of 317 samples were tested.
. There were no incorrect calls
. Six samples (1.9%) had to be repeated because of "no call" due to NTCE is reported when the quality or quantity of the DNA in the sample/PCR product is poor. All six no calls gave correct calls upon the repeat for a 100% agreement of the INFINITI CYP2C19 Assay with bi-directional sequencing. The repeat test was done on the same extracted DNA. Only one repeat was done for each sample.

The results of the comparison studies comparing the INFINITI CYP2C19 Assay to bi-directional sequencing are provided in Table 3.

Genotype	Number Tested	Replicates per Sample	Number of Correct Genotype Calls	No Calls	Agreement	95% One-sided Confidence Lower Limit
1/1	105	1	103	2	98.1%	95.0%
1/2	80	1	77	3	96.2%	91.5%
2/2	12	1	12	0	100%	95.8%
1/3	8	1	8	0	100%	93.8%
3/3	1	1	1	0	100%	50.0%
1/17	74	1	73	1	98.6%	95.3%
17/17	16	1	16	0	100%	96.9%
2/3	4	1	4	0	100%	87.5%
2/17	16	1	16	0	100%	96.9%
3/17	1	1	1	0	100%	50.0%
Total	317	1	311	6	98.1%	96.4%

Table 3 Agreement between INFINITI CYP2C19 Assay with Bi-directional Sequencing

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

Assay Inter-Laboratory Reproducibility

A three-site study was conducted to demonstrate the reproducibility of the INFINITI CYP2C19 Assay. The study involved three identical lots of the INFINITI CYP2C19 Assay, four operators, and four instruments (one site ran two sets of reproducibility studies, each with a different operator and instrument).

5

The sites ran identical samples comprised of 12 whole blood samples. The sites were blinded to sample identity. At each site, each sample was run in duplicate per day/operator for five non-consecutive days. A total of 430 tests were run. Of the 430 samples assayed, 14 samples (3.3%) had to be repeated due to "No Calls". The samples were repeated using the same extracted DNA. These NTCE errors might have been caused by temperature gradient during PCPc.imrooner sealing of the PCR tubes, or operator pipetting error. The genotype calls from the repeat assays were 100% correct, There was one incorrect call (*1/*2 instead of *2/*2). The root cause of the incorrect call was not definitively determined.

Results of the inter-laboratory reproducibility study are summarized in Table 4a and Table 4b.

| Genotype* | Samples
Tested | Siteb | Replicates
per Site | Replicates with Calls made by
INFINITI | Correct
Calls | Incorrect
Callsd | No
Callse | % Correct
Callsf | 95% One-sided
Confidence -
Lower Limitg |
|-----------|-------------------|-- | *1/*1 | 2 | | | | | | | *1/*2 | 3 | | | | | | | *2/*2 | 2 | | | | | | | *1/*3 | 1 | | | | | | | *1/*17 | 2 | | | | | | | *17/*17 | 2 | | | | | | | Total | 12 Genotype
-----|------------------------|-------------------------------------------------------|------------------|---------------------|--------------|---------------------|-----------------------------------------------|
| 1 | 40 | 39 | 39 | 0 | 1 | 97.5 | 91.4 |
| 2 | 20 | 20 | 20 | 0 | 0 | 100 | 97.5 |
| 3 | 10 | 10 | 10 | 0 | 0 | 100 | 95.0 |
| total | 70 | 69 | 69 | 0 | 1 | 98.6 | 95.1 |
| 1h | 40 | 40 | 40 | 0 | 0 | 100 | 98.8 |
| 2 | 30 | 30 | 30 | 0 | 0 | 100 | 98.3 |
| 3 | 30 | 30 | 30 | 0 | 0 | 100 | 98.3 |
| total | 100 | 100 | 100 | 0 | 0 | 100 | 99.5 |
| 1 | 40 | 39 | 38 | 1 | 1 | 95.0 | 87.0 |
| 2 | 20 | 20 | 20 | 0 | 0 | 100 | 97.5 |
| 3 | 20 | 14 | 14 | 0 | 6 | 70.0 | 47.4 |
| total | 80 | 73 | 72 | 1 | 7 | 90.0 | 82.8 |
| 1 | 20 | 20 | 20 | 0 | 0 | 100 | 97.5 |
| 2 | 10 | 10 | 10 | 0 | 0 | 100 | 95.0 |
| 3 | 10 | 10 | 10 | 0 | 0 | 100 | 95.0 |
| total | 40 | 40 | 40 | 0 | 0 | 100 | 98.8 |
| 1 | 40 | 39 | 39 | 0 | 1 | 97.5 | 91.4 |
| 2 | 20 | 17 | 17 | 0 | 3 | 85.0 | 66.9 |
| 3 | 10 | 9 | 9 | 0 | 1 | 90.0 | 66.4 |
| total | 70 | 65 | 65 | 0 | 5 | 92.9 | 86.1 |
| 1 | 40 | 40 | 40 | 0 | 0 | 100 | 98.8 |
| 2 | 20 | 19 | 19 | 0 | 1 | 95.0 | 82.9 |
| 3 | 10 | 10 | 10 | 0 | 0 | 100 | 95.0 |
| total | 70 | 69 | 69 | 0 | 1 | 98.6 | 95.1 |
| All | 430 | 416 | 415 | 1d | 14e | 96.5 | 94.7 |

Table 4a Inter-Laboratory Reproducibility of the INFINITI CYP2C19 Assay by Genotype Call

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

ь Internal site (Site 1) had two sets, one operator each

ﺑ Excludes samples with No Calls

o Initial result was incorrect (*1/*2 instead of *2/*2). The root cause of the incorrect call was not definitively determined.

One no call was due to Registration Spot Error - this error is reported when the microarray chip is not properly aligned. Repear test gave the correct call

13 reported NTCE Error - NTCE is reported if the quality of the DNA in the sample/PCR product is poor. Repeat tests gave the correct calls

{ Samples with correct calls/samples tested

8 Site 3: one sample had A260/A280 of 1.16 (1.6 is required), therefore only one sample was tested

h Site 1: one sample had A260/A280 of 1.46 (1.6 is required), therefore only two samples were tested

.. -Site 3: one sample had A260/A280 of 1.46 (1.6 is required), therefore only one sample was tested

J Site 3: one sample had A260/A280 of 1.45 (1.6 is required), therefore only one sample was tested

6

Table 4b	Inter-Laboratory Reproducibility of the INFINITI CYP2C19 Assay by Sample
Sample ID	Genotype	Replicates per sample	Replicates with Genotype Calls made by INFINITI	Samples with Correct Calls	Samples with No Calls	Samples with Incorrect Calls	Correct Call Rate (%)	95% One-sided Confidence Lower Limit
1	2/2	40	38	37	2	1	92.5	83.1
2	2/2	40	35	35	5	0	87.5	76.0
3	17/17	40	39	39	1	0	97.5	91.4
4	1/17	40	37	37	3	0	92.5	83.1
5	1/3	40	40	40	0	0	100	98.8
6	1/2	40	40	40	0	0	100	98.8
7	1/2	40	40	40	0	0	100	98.8
8	1/1	30	29	29	1	0	96.7	88.6
9	17/17	30	29	29	1	0	96.7	88.6
10	1/1	40	40	40	0	0	100	98.8
11	1/17	30	29	29	1	0	96.7	88.6
12	1/2	20	20	20	0	0	100	97.5
	All	430	416	415	14	1	96.5	94.7

Table 4b Inter-Laboratory Reproducibility of the INFINITI CYP2C19 Assay by San

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

b Excludes samples with No Calls

& A sample with correct call indicates a correct call at all loci.

4 One no call was due to Registration Spot Error - this error is reported when the microarray chip is not properly aligned. Repeat test gave the correct call; 13 reported NTCE is reported if the quality or quantity of the DNA in the sample/PCR product is poor. Repeat tests gave the correct calls

6 Initial result was incorrect (*1/*2 instead of *2/*2). The root cause of the incorrect call was not definitively determined

{ Samples with correct calls/samples tested

Additional reproducibility studies were conducted at the same three sites to demonstrate the reproducibility of the INFINITI CYP2C19 Assay for additional samples including *2/*3. The study involved three lots of the INFINITI CYP2C19 Assay. The sites ran identical samples comprised of six (6) genomic whole blood samples. The sites were blinded to sample identity. At each sample was run in triplicate per day/operator for five nonconsecutive days.

A total of 255 tests were completed. Overall correct call rate for the first time run was 97.6%. There were no incorrect calls. There were six no calls:

One no call was due to Registration Spot Error is reported when the microarrav chip is not properly , ● aligned.
- Five were due to NTCE error. NTCE is reported if the quality of the DNA in the sample/PCR . product is poor. These NTCE errors might have been caused by temperature gradient during PCR, improper sealing of the PCR tubes, or operator pipetting error.

Results of the inter-laboratory reproducibility studies are summarized in Table 5b.

7

| Genotype | Samples
Tested | Site | Replicates
per Site | Replicates
with Genotype
Calls made by
INFINITI | Correct
Calls | Incorrect
Calls | No
Calls | % Correct
Calls | 95% One-sided
Confidence
Lower Limit |
|----------|-------------------|-------|------------------------|----------------------------------------------------------|------------------|--------------------|-------------|--------------------|--------------------------------------------|
| *1/*1 | 1 | 1 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 2 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 3 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | Total | 45 | 45 | 45 | 0 | 0 | 100 | 98.9 |
| *1/*2 | 1 | 1 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 2 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 3 | 15 | 13 | 13 | 0 | 2 | 86.7 | 66.1 |
| | | Total | 45 | 43 | 43 | 0 | 2 | 95.6 | 88.4 |
| *1/*3 | 1 | 1 | 0 | n/a | n/a | n/a | n/a | n/a | n/a |
| | | 2 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 3 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | Total | 30 | 30 | 30 | 0 | 0 | 100 | 98.3 |
| *1/*17 | 1 | 1 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 2 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 3 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | Total | 45 | 45 | 45 | 0 | 0 | 100 | 98.9 |
| *2/*3 | 1 | 1 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 2 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 3 | 15 | 12 | 12 | 0 | 3 | 80.0 | 56.4 |
| | | Total | 45 | 42 | 42 | 0 | 3 | 93.3 | 84.9 |
| *2/*17 | 1 | 1 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 2 | 15 | 15 | 15 | 0 | 0 | 100 | 96.7 |
| | | 3 | 15 | 14 | 14 | 0 | 1 | 93.3 | 77.4 |
| | | Total | 45 | 44 | 44 | 0 | 1 | 97.8 | 92.4 |
| Total | 6 | All | 255 | 249 | 249 | 0 | 6 | 97.6 | 95.6 |

Tahla Ea

ª Determined by bi-directional sequencing; * 1/* 1 samples are wild-type for * 2, * 3 and * 1 7

b Excludes samples with No Calls

One no call was due to Registration Spot Error - this error is reported when the microarray chip is not properly aligned, 5 reported NTCE Error - NTCE is reported if the quality of the DNA in the sample/PCR product is poor.

d Samples with correct calls/samples tested

Site I: DNA concentration was 8ng/ul, below the LOD of 10ng/ul, therefore no sample tested

| Sample
ID | Genotype* | Replicates
per sample | Replicates
with Genotype
Calls made by
INFINITI* | Correct
Calls | No Calls* | Incorrect
Calls | Correct Call
Rate* (%) | 95% One-sided
Confidence Lower
Limit |
|--------------|-----------|--------------------------|-----------------------------------------------------------|------------------|-----------|--------------------|---------------------------|--------------------------------------------|
| 1 | *1/*3 | 30 | 30 | 30 | 0 | 0 | 100 | 98.3 |
| 2 | *1/*17 | 45 | 45 | 45 | 0 | 0 | 100 | 98.9 |
| 3 | *1/*1 | 45 | 45 | 45 | 0 | 0 | 100 | 98.9 |
| 4 | *2/*17 | 45 | 44 | 44 | 1b | 0 | 97.8 | 92.4 |
| 5 | *2/*3 | 45 | 42 | 42 | 3 | 0 | 93.3 | 84.9 |
| 6 | *1/*2 | 45 | 43 | 43 | 2 | 0 | 95.6 | 88.4 |
| All | | 255 | 249 | 249 | 6 | 0 | 97.6 | 95.6 |

Table 5h, Inter-Laboratory Reproducibility of the INFINITI CYP2C19 Assay by Sample

4 Genotype determined by bi-directional sequencing; * 1/* 1 samples are wild-type for *2, * 3 and * 1 7

b Excludes samples with No Calls

← A sample with correct call indicates a correct call at all loci.

4 One no call was due to Registration Spot Error - this error is reported when the microarray chip is not properly aligned; 5 reported NTCE Error - NTCE is reported if the quality or quantity of the DNA in the sample/PCR product is poor.

° Samples with correct calls/samples tested

8

Table 6 provides a summary of the combined reproducibility studies.

| Genotype* | Samples
Tested | Replicates
per Sample | Replicates
with Genotype
Calls made by
INFINITIb | Correct
Callsc | No Callsd | Incorrect
Callse | Correct Call
Ratef (%) | 95% One-sided
Confidence Lower
Limit |
|-----------|-------------------|--------------------------|-----------------------------------------------------------|-------------------|-----------|---------------------|---------------------------|--------------------------------------------|
| *1/*1 | 3 | 115 | 114 | 114 | 1 | 0 | 99.1 | 97.0 |
| *1/*2 | 4 | 145 | 143 | 143 | 2 | 0 | 98.6 | 96.4 |
| *2/*2 | 2 | 80 | 73 | 72 | 7 | 1 | 90.0 | 82.8 |
| *1/*3 | 2 | 70 | 70 | 70 | 0 | 0 | 100 | 99.3 |
| *1/*17 | 3 | 115 | 110 | 110 | 5 | 0 | 95.7 | 915 |
| *17/*17 | 2 | 70 | 69 | 69 | 1 | 0 | 98.6 | 95.1 |
| *2/*3 | 1 | 45 | 42 | 42 | 3 | 0 | 93.3 | 84.9 |
| *2/*17 | 1 | 45 | 44 | 44 | 1 | 0 | 97.8 | 92.4 |
| Total | 18 | 685 | 665 | 664 | 20 | 1 | 96.9 | 95.6 |

Table 6: Summary of the Inter-Laboratory Reproducibility of the INFINITI CYP2C19 Assay, by Genotype calls

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

b Excludes samples with No Calls

€ A sample with correct call indicates a correct call at all loci.

d Two no calls were due to Registration Spot Error is reported when the microarray chip is not properly aligned; 18 reported NTCE Error - NTCE is reported if the quality of the DNA in the sample/PCR product is poor.

& Initial result was incorrect (*1/*2 instead of *2/*2). The root cause of the incorrect call was not definitively determined.

f Samples with correct calls/samples tested

Interference

Interference from potential interfering substances was evaluated using eight (8) whole blood samples. The potential interfering substances were added separately to the whole blood sample prior to DNA extraction and testing with the INFINITI CYP2C19 Assay. Genotype results were compared to those obtained from non-spiked samples. Sample genotype was verified by bi-directional DNA sequencing. The interference studies demonstrated that the INFINITI CYP2C19 Assay performance was not affected by the addition of the following substances.

Substance Added	Concentration
Bilirubin (conjugated)	60mg/dl
Bilirubin (unconjugated)	60mg/dl
Triglycerides (Intralipid)	3000mg/dl
Human albumin	6g/dl

No studies were conducted with oral anti-coagulants, and no claims are being made.

Sample Carry-Over

No sample carry-over was detected when 300ng of a positive sample was followed by 10ng of a second positive sample, and when 300ng of a positive sample was followed by a "No Template Control" or water. All genotype calls were 100% correct.

Reagent Stability

BioFilmChip Microarray:	12 months at RT (15 to 30°C)
Intellipac Reagent:	12 months Refrigerated (2 to 8°C)
Amplification Mix:	18 months Frozen (-30 to -15°C)

Conclusion

The above pre-clinical and clinical data support the safety and effectiveness of the INFINITI CYP2C19 Assay.

9

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

AutoGenomics, Inc. c/o Evelyn Lopez Vice President, Regulatory Affairs 2980 Scott Street Vista, CA 92081

OCT 2 5 2010

Re: K101683

Trade/Device Name: INFINITI CYP2C19 Assay Regulation Number: 21 CFR §862.3360 Regulation Name: Drug Metabolizing Enzyme Genotyping System Regulatory Class: Class II Product Codes: NTI, NSU Dated: October 6, 2010 Received: October 8, 2010

Dear Evelyn Lopez:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to.895. 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 of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

10

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. 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 Small Manufacturers, International and Consumer Assistance at its toll-fre number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

GJC.

Courtney Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

11

AutoGenomics, Inc.

Premarket Notification 510(k) INFINITI® CYP2C19 Assay

Indications for Use

1111683 OCT 25 2010

510(k) Number (if known):

Device Name:

Indications For Use:

K101683

INFINITI®CYP2C19 Assay

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 CYP2C19 Assay is a qualitative assay for use in clinical laboratories upon prescription by the attending physician.

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 non-response.

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 IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Signature

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

in 10168 510(k) _

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