Predicate Devices

AmpliChip CYP450 Test for CYP2C19 (K043576), INFINITI System Assay for Factor II & Factor V (K060564)

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on standard molecular biology techniques (PCR, hybridization, microarray) and automated processing, with no mention of AI or ML in the signal analysis or genotype calling.

Therapeutic

No.
This device is an in vitro diagnostic test designed to detect genetic variants related to warfarin sensitivity, which provides information for physicians but does not directly treat or prevent a disease.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that it is an "in vitro diagnostic test" and is "indicated for use to identify individuals at risk for sensitivity to warfarin." The "Device Description" also refers to it as an "in vitro diagnostic device."

SaMD (Software as a Medical Device)

No

The device description explicitly states it is an in vitro diagnostic device utilizing proprietary film-based microarray technology, reagent management, and process automation, in addition to software technology. It also lists hardware components like the BioFilmChip™ Microarray, Intellipac Reagent Module, PCR Amplification Mix, and requires the use of the AutoGenomics INFINITI Analyzer. This indicates it is a system with significant hardware components, not a software-only device.

IVD (In Vitro Diagnostic)

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

Here's why:

Explicitly Stated in Intended Use and Device Description: The document repeatedly refers to the device as an "in vitro diagnostic test" and "in vitro diagnostic device."
Analyzes Samples from the Human Body: The assay uses genomic DNA obtained from EDTA-anticoagulated whole blood samples.
Provides Information for Clinical Use: The intended use states it's for "use in clinical laboratories upon prescription by the attending physician" and is "indicated for use to identify individuals at risk for sensitivity to warfarin." This information is used to aid in clinical decision-making.
Performs Tests Outside the Body: The entire process of DNA extraction, amplification, hybridization, and analysis is performed in a laboratory setting, outside of the patient's body.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is an in vitro diagnostic test for the detection and genotyping of the *2 and *3 CYP4502C9 genetic variants and the VKORC1 3673 (-1639) intronic variant in genomic deoxyribonucleic acid (DNA) obtained from EDTA-anticoagulated whole blood samples. The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is a qualitative assay for use in clinical laboratories upon prescription by the attending physician.
The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is indicated for use to identify individuals at risk for sensitivity to warfarin.

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

ODW, ODV, NSU

Device Description

The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin 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 2C92, 2C93, and VKORC1 3673 (-1639) mutations from EDTA-anticoagulated whole blood samples.

The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is comprised of the BioFilmChip™ Microarray, the Intellipac Reagent Module and the PCR Amplification Mix. The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin 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 to eight reservoirs that house the test reagents and has an integrated memory chip. Information on the reagent such as lot number, expiration date and volume usage, are archived in the memory.

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

The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin 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 [determination of the 2C92, 2C93 and VKORC1 3673 (-1639) genotypes]
Steps (c) through (f) are automated by the INFINITI Analyzer.

The INFINITI Analyzer automates the 2C9 and VKORC1 assays and integrates all the discrete processes of sample (PCR amplicon) handling, reagent management, hybridization, detection, and results analysis. 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

For use in clinical laboratories upon prescription by the attending physician.

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

The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin 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 2C9-VKORC1 Multiplex Assay for Warfarin. All samples used in the comparison studies at the three sites were from patients using or have used warfarin. Patient samples were de-identified to protect patient's identity. Each site performed the DNA extraction using a different extraction method.

Sample Size: 150 samples for 2C92, 150 for 2C93, 150 for VKORC1 3673 (-1639), and 450 total for assay (Table 2a).
Table 2b shows analysis by sample type with columns like "Samples Tested" which sum to 150.
For inter-laboratory reproducibility study: Identical samples comprised of seven genomic DNA samples and five whole blood samples. Samples for the reproducibility study totaled 432 for 2C9 and 432 for VKORC1 (Table 3a and 3b indicate totals per site and total for assay as 1296 tests total across 3 sites).

Annotation Protocol: Genotype determined through bi-directional DNA sequencing.

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

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

Limit of Detection (analytical sensitivity): Serial dilutions (200, 100, 50, 25, 10, 1, 0.1ng DNA) from known purified DNA sample. Each dilution assayed three times.

Sample Size: Not explicitly stated beyond "known purified DNA sample" and each dilution assayed three times.
Key Results: Established minimum DNA concentration to be 1ng DNA. Recommended DNA concentration for the assay is 25ng/ul. 50ng per test is required. Concentrations of 100ng and 200ng did not interfere. At 0.1ng DNA, there were "No call" results failing in 2 out of 3 runs for 2C9*2.

Percent Agreement vs. Bi-directional Sequencing (Comparison Study):

Study Type: Comparison study.
Sample Size: 150 samples per genetic variant (2C92, 2C93, VKORC1 3673 (-1639)), total 450 tests.
Key Results:
- 98.0% agreement for 2C9*2 (147/150 total correct genotype calls, 3 no calls, 0 incorrect calls, 95% One-Sided Confidence Lower Limit of 95.09%)
- 97.3% agreement for 2C9*3 (146/150 total correct genotype calls, 3 no calls, 1 incorrect call, 95% One-Sided Confidence Lower Limit of 94.09%)
- 98.0% agreement for VKORC1 3673 (-1639) (147/150 total correct genotype calls, 3 no calls, 0 incorrect calls, 95% One-Sided Confidence Lower Limit of 95.09%)
- Overall assay agreement: 97.8% (440/450 total correct, 9 no calls, 1 incorrect call, 95% One-Sided Confidence Lower Limit of 96.86%) (First Time Run)
- Agreement by Sample Type (Final Result): 99.3% (149/150) for 2C9.
- Note: One incorrect call for 2C9*3 was noted ("Initial INFINITI results (*1/1 for 2C92, *1/3 for 2C93 and GG for VKORC1 3673) did not match bi-directional sequence results (*1/1 for 2C92, *1/1 for 2C93 and GG for VKORC1 3673). The same INFINITI results were obtained on repeat run. Reason unknown.")

Assay Inter-Laboratory Reproducibility:

Study Type: Multi-site reproducibility study.
Sample Size: Seven genomic DNA samples and five whole blood samples, run in duplicate per day/operator for six days, with three operators per site. Total tests per site: 432. Total for Assay across 3 sites: 1296.
Key Results (First Time Run):
- Total for 2C9: 99.07% correct calls (428 correct/432 total for site (average), 98.06% 95% One-Sided Confidence Lower Limit).
- Total for VKORC1: 97.22% (average for VKORCI 673 (-1639 GA), 92.73% 95% One-Sided Confidence Lower Limit).
- Total for VKORC1 was 99.3% (427 correct/432 total for site (average), 97.72% 95% One-Sided Confidence Lower Limit).
- Overall for Assay (first time run): 98.99% correct (1283 correct/1296 total tests, 98.42% 95% One-Sided Confidence Lower Limit).
Key Results (Final Result):
- Total for 2C9: 99.88% (99.53%-99.88% 95% One-Sided Confidence Lower Limit).
- Total for VKORC1: 99.72% (99.72%-99.30% 95% One-Sided Confidence Lower Limit for different genotypes).
- Overall for Assay (final result): 99.96% (99.96% 95% One-Sided Confidence Lower Limit).

Drug Interference:

Study Type: Interference study.
Key Results: No interference from 8mg/dl bilirubin, 70mg/dl cholesterol, and 133v/dl heparin.

Sample Carry-Over:

Study Type: Carry-over study.
Key Results: No sample carry-over when 300ng of positive sample followed by 10ng of second positive sample, or by "No Template Control" or water. All genotype calls were 100% correct.

Assay Interference:

Study Type: Interference study between assays.
Key Results: Running the subject device and the INFINITI Assay for Factor II & Factor V on the same instrument did not affect the results of either assay.

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

Percent Agreement:
- 2C9*2: 98.0%
- 2C9*3: 97.3%
- VKORC1 3673 (-1639): 98.0%
- Total for Assay (comparison): 97.8%
Correct Call Rates (Reproducibility - First Time Run):
- Total for 2C9: 99.07%
- Total for VKORC1: 98.84%
- Total for Assay (reproducibility): 98.99%
Correct Call Rates (Reproducibility - Final Result):
- Total for 2C9: 99.88%
- Total for VKORC1: 99.83%
- Total for Assay (reproducibility): 99.96%

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.

AmpliChip CYP450 Test for CYP2C19 (K043576), INFINITI System Assay for Factor II & Factor V (K060564)

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

K073014

510(K) SUMMARY

。

| Submitted By | AutoGenomics, Inc.
2251 Rutherford Road
Carlsbad, CA 92008, USA
Telephone: (760) 804-7378
FAX: (760) 804-7382 | JAN 23 2008 | |
|----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------|--|
| | Contact: Evelyn Lopez
Vice President, Regulatory Affairs | | |
| | Date Prepared: January 11, 2008 | | |
| Device Name | Trade or Proprietary Name: INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin
Common or Usual Name: 2C9 and VKORC1 Drug Metabolizing Enzyme Genotyping System | | |
| Regulations and
Product Codes | Regulations: 21CFR§862.3360 Drug Metabolizing Enzyme Genotyping Systems
21CFR§864.7750 Prothrombin Time Test
21CFR§862.2570 Instrumentation for Clinical Multiplex Test Systems
Product Codes: ODW Cytochrome P450 2C9 (CYP450 2C9) Drug Metabolizing Enzyme Genotyping System
ODV Vitamin K epoxide reductase complex subunit 1 (VKORC1) Genotyping System
NSU Instrumentation for Clinical Multiplex Test Systems | | |
| Predicate Device | (a) AmpliChip CYP450 Test for CYP2C19
(b) INFINITI System Assay for Factor II & Factor V | | |
| Device Description | The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin 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 2C92, 2C93, and VKORC1 3673 (-1639) mutations from EDTA-anticoagulated whole blood samples.

The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is comprised of the BioFilmChip™ Microarray, the Intellipac Reagent Module and the PCR Amplification Mix. The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin 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 to eight reservoirs that house the test reagents and has an integrated memory chip. Information on the reagent such as lot number, expiration date and volume usage, are archived in the memory. | | |

1

| | The PCR Amplification Mix consists of the reagents needed for the PCR amplification
step of the assay. |
|----------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin 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 [determination of the 2C92, 2C93 and VKORC1
3673 (-1639) genotypes]
Steps (c) through (f) are automated by the INFINITI Analyzer. |
| | The INFINITI Analyzer automates the 2C9 and VKORC1 assays and integrates all the
discrete processes of sample (PCR amplicon) handling, reagent management,
hybridization, detection, and results analysis. The assays are processed automatically and
read by the built-in confocal microscope. Results are analyzed and presented as genotype
calls. |
| Intended Use | The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is an in vitro diagnostic
test for the detection and genotyping of the *2 and *3 CYP4502C9 genetic variants and
the VKORC1 3673 (-1639) intronic variant in genomic deoxyribonucleic acid (DNA)
obtained from EDTA-anticoagulated whole blood samples. The INFINITI 2C9 &
VKORCI Multiplex Assay for Warfarin is a qualitative assay for use in clinical
laboratories upon prescription by the attending physician. |
| Indication for Use | The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is indicated for use to
identify individuals at risk for sensitivity to warfarin. |
| Substantial
Equivalence | Tables 1a and 1b provide a comparison of the technological
characteristics of the INFINTI 2C9 & VKORC1 Multiplex Assay for Warfarin to those of
the predicate devices
• AmpliChip CYP450 Test for CYP2C19 (K043576) |

:

. . INFINITI System Assay for Factor II & Factor V (K060564)

Table 1a

| Characteristics | Predicate
AmpliChip CYP450 Test for CYP2C19 | Subject Device
INFINITI 2C9 & VKORC1
Multiplex Assay for Warfarin |
|----------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------|
| 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 human blood samples | Same |
| Reaction Conditions | Utilizes thermal cycling Utilizes 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 |
| Differences | | |
| Gene | CYP2D6 and CYP2C19 | CYP2C9 and VKORC1 |
| Microarray substrate | Reactions occur on a single glass slide | Reactions occur on a single biofilm
microarray chip |
| Number of alleles | 2 | 3 |

2

Table 1b

	Predicate	Subject Device
Characteristics	INFINITI System Assay for
Factor II & Factor V	INFINITI 2C9 & VKORC1
Multiplex Assay for Warfarin
	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 human blood samples	Same
Reaction Conditions	Utilizes thermal cycling Utilizes target DNA amplification	Same
Microarray substrate	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
	Differences
Gene	Factor II and Factor V	CYP2C9 and VKORC1
Number of alleles	2	3

Performance

The following are performance characteristics of the INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin:

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)

Serial dilutions (200, 100, 50, 25, 10, 1, 0.1ng DNA) were prepared from a known purified DNA sample. Each serial dilution was assayed three times using the INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin. The study established the minimum DNA concentration for the INFINITI System Assay for 2C9-VKORC1 to be Ing DNA. The recommended DNA concentration for the INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is 25ng/ul. The assay requires 2ul of DNA sample or the equivalent of 50ng per test.

In addition, the same study demonstrated that DNA concentrations of 100ng and 200ng, which were in excess of the recommended concentration (50ng), did not interfere with the INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin. The following table provides a summary of the results of the study.

Sample			Run 1				Run 2				Run 3
ng DNA	Genotype		Genotype Calls			Result	Genotype Calls			Result	Genotype Calls			Result
	2C9	VKORCI
3673 (-1639)	2C9
*2	2C9
*3	VKORCI
3673 (-1639)		2C9
*2	2C9
*3	VKORCI
3673 (-1639)		2C9
*2	2C9
*3	VKORCI
3673 (-1639)
200	W	H	W	W	H	Pass	W	W	H	Pass	W	W	H	Pass
100	W	H	W	W	H	Pass	W	W	H	Pass	W	W	H	Pass
50	W	H	W	W	H	Pass	W	W	H	Pass	W	W	H	Pass
25	W	H	W	W	H	Pass	W	W	H	Pass	W	W	H	Pass
10	W	H	W	W	H	Pass	W	W	H	Pass	W	W	H	Pass
1	W	H	W	W	H	Pass	W	W	H	Pass	W	W	H	Pass
0.1	W	H	No call	W	H	Fail	W	W	H	Pass	No call	W	H	Fail

Limit of Detection

3

Percent Agreement vs. Bi-directional Sequencing

The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin 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 2C9-VKORC1 Multiplex Assay for Warfarin. All samples used in the comparison studies at the three sites were from patients using or have used warfarin. Patient samples were de-identified to protect patient's identity. Each site performed the DNA extraction using a different extraction method. The results of the comparison studies demonstrated

98.0% agreement for 2C92 as compared with bi-directional sequencing on 1st run 97.3% agreement for 2C93 as compared with bi-directional sequencing on 15 run 98.0% agreement for VKORC1 3673 (-1639) as compared with bi-directional sequencing on 1st run

The results of the comparison studies are summarized in Table 2a and Table 2b.

Table 2a Agreement between INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin and Bi-Directional DNA Sequencing

| Genotype" | Number
Tested | Replicates
per Sample | Number of
Correct
Genotype Calls" | Number of
Incorrect Calls | No Calls | Agreement | 95% One-
Sided
Confidence
Lower
Limit |
|-------------------------------------|------------------|--------------------------|-----------------------------------------|------------------------------|----------|-----------|---------------------------------------------------|
| 2C9*2
*1/2 | 35 | 1 | 34 | 0 | 1 | 97.1% | 88.82% |
| 2C92
*2/2 | 2 | 1 | 2 | 0 | 0 | 100.0% | 50%d |
| 2C92
1/1 | 113 | 1 | 111 | 0 | 2 | 98.2% | 94.91% |
| Total for 2C92 | 150 | 1 | 147 | 0 | 3 | 98.0% | 95.09% |
| 2C93
*1/3 | 19 | 1 | 19 | 0 | 0 | 100.0% | 80.45% |
| 2C93
*3/3 | 1 | 1 | 1 | 0 | 0 | 100.0% | 0%d |
| 2C93
*1/1 | 130 | 1 | 126 | 1c | 3 | 96.9% | 94.30% |
| Total for 2C93 | 150 | 1 | 146 | 1 | 3 | 97.3% | 94.09% |
| VKORCI
3673 (-1639)
GA | 63 | 1 | 62 | 0 | 1 | 98.4% | 93.74% |
| VKORCI
3673(-1639)
AA | 27 | 1 | 25 | 0 | 2 | 92.6% | 79.01% |
| VKORCI
3673 (-1639)
GG | 60 | 1 | 60 | 0 | 0 | 100.0% | 98.33% |
| Total for
VKORCI
3673 (-1639) | 150 | 1 | 147 | 0 | 3 | 98.0% | 95.09% |
| Total for
Assay | 450 | 1 | 440 | 1 | 9 | 97.8% | 96.86% |

a Genotype determined through bi-directional DNA sequencing

b Calls produced on first run

් Initial INFINITI results (*1/1 for 2C92, *1/3 for 2C93 and GG for VKORC1 3673) did not match bi-directional sequence results (*1/1 for 2C92, *1/1 for 2C93 and GG for VKORC1 3673). The same INFINITI results were obtained on repeat run. Reason unknown.

d For sample sizes 1 and 2, and 100% agreement, SE(p2-p1)=0. Pure sample size correction for sample size 2 is 50% and for sample size 1 is 100%, therefore, One-Sided Confidence Lower Limits are 50% (n=2) and 0% (n=1).

4

Sample Description Genotype*				First Time Run				Final Resultd
2C9	VKORC1
3673 (-1639)	*2	*3	# Samples Tested	Samples with Genotype Calls made by INFINITIb	Samples with Correct Callsc	Samples with No Incorrect Calls	Samples with Genotype Calls made by INFINITIb	Samples with Correct Callsc	Samples with No Incorrect Calls	Correct Call Ratee (%)
	1/1	]/]	]/]	20	18	18	2	20	20	0	90.0
	1/1	1/1	1/1	34	34	34	0	34	34	0	100
	1/1	1/1	1/1	43	43	42	0	43	42	1	97.7 (42/43)
	1/2	1/1	1/1	4	4	4	0	4	4	0	100
	1/2	1/1	1/1	15	14	14	1	15	15	0	100
	1/2	1/1	1/1	12	12	12	0	12	12	0	100
	1/1	1/3	1/1	2	2	2	0	2	2	0	100
	1/1	1/3	1/1	10	10	10	0	10	10	0	100
	1/1	1/3	1/1	3	3	3	0	3	3	0	100
	2/2	1/1	1/1	1	1	1	0	1	1	0	100
	2/2	1/1	1/1	1	1	1	0	1	1	0	100
	1/2	1/3	1/1	1	1	1	0	1	1	0	100
	1/2	1/3	1/1	2	2	2	0	2	2	0	100
	1/2	1/3	1/1	1	1	1	0	1	1	0	100
	1/1	3/3	1/1	1	1	1	0	1	1	0	100
Total				150	147	146	3	150	149	1	99.3 (149/150)

able 2b Agreement between INFINITI 2C9 & VKORCI Multiplex Assay for Warfarin and Bi-Directional DNA Sequencing (by Sample Type

Advance Section

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Assay Inter-Laboratory Reproducibility

A three-site study was conducted to demonstrate the reproducibility of the INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin. The study involved three identical lots of the INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin. The sites ran identical samples comprised of seven genomic DNA samples and five whole blood samples. The sites were blinded to sample identity. Each site used a different DNA extraction method. At each site, each sample was run in duplicate per day/operator for six days. Three operators were required for each site. Results of the inter-laboratory reproducibility study are summarized in Tables 3a and 3b.

6

ble 3a Inter-Laboratory Reproducibility of the INFINITI 2C9							First Time Run	KORC1 Multiplex Assay for Warfarin by Genotype ca				inal Result
enotyp	Gamples Tested	Tests Per Site	Site	Genotype Calls									96
					Correc Calls	Incorrect Calls	נקום קנטו	% Correc	95% One-Side Confidence Lower Limit	Correct Calls	ncorrec . Calls	ות היום	Correc Calls	5% One-Side Confidence Lower Limit
			{	98	98			100			0	0	100
て #/ # これだと	క్	98	ट	9E	ਡ		ಲ್ಲಿ	94.4		9 2018	0	0	100
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			ໄ	96			r I	99.0		96	00000	0	100
【 #/ # C #637	8	96	ਟ	96	તેણ		0	1 00		96		0	100
			દ	96	96		0	100		96		0	100
			ota	288	287		ໄ	99.65	99.13			0	100	09.83
otal for 2C9				432	428		t	99.07	98.06%	2017 882	0	0	100	99.88
				24				100			0	0	100
€ * / ½ § * 63	ಒಂದಿಗಳು ಒಂದು ಒಂದು ಮಾರ್ಥಿಗಳು ಒಂದು ಮಾರ್ಥಿಗಳು ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾರ್ಗ್ ಮಾಡಿ ಮಾರ್ಗ್ ಮಾಡಿ ಮಾರ್ಗ್ ಮಾಡಿ ಮಾರ್ಗ್ ಮಾಡಿ ಮಾರ್ಗ್ ಮಾಡಿ ಮಾರ್ಗ್ ಮಾಡಿ ಮಾರ್ಗ್ ಮಾಡಿ ಮಾರ್ಗ್ ಮಾಡಿ ಮಾರ್	র ব	ਟ	ਦੇ ਇੱਕ	ਟੂਰ ਦੇ ਇੱਕ		ofic	91.7			0	0	I OO
			ది					1 00			0	0	100
			tola		70		0 N	97.22	92.73%		0	0	100	99.30%
			ໄ	ਹੈ। ਇਹ	ਲ ਕ		0	100			0	0	100
E #16 # E#637	ਟ	র ব	ত্র				ﺳﺎﺗﮫ ﮨﮯ	100		지지만 지지자 지원	0	0	100
			દુ	র্যা	ದ್ದ ಪ್ರಸಿದ್ದ ಮತ್ತು ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ ಮಾಡಿ			05.8			0 0	0	100
			tota	ਟ (				98.6	95.21%			0 ﺍﻟﻤ	100	99.30%
				96	SS		g I	99.0		96	0		100
T #/ I * E #637	8	96	ત્યાળ	ેણ	તેરે રે		վ մ	99.0		96	0 0	0 0	100
				ഴു	982 96		0	100		887 96			1 00
			ota	288				99.3	98.17%		0		100
otal for 2C9				432	427		2000	98.84	97.72%	432	0 0	0 0	1 00	99.83% 99.88%
				60	09			100		09		0	100
	רי	09	ਟ	60	રતે			98.3		09	0	0	100
VKORCI 673 (-1639 GA			ర్థి మూలాలు కార్యాలయం గ్రామం నుండి 10 కి.మీ. దూరంలో ఉన్నాయి. ప్రాథమిక ఆరోగ్యం మూలాలు విద్యా శిశు సంరక్షణ కార్యాలయం విశాఖపట్నం మూలాలు విశాఖపట్నం మూలాలు విశాఖపట్నం క	60	60		0	1 00		09	0	0	100
			tota	186	179		l	99.44	98.08%	180	0	0	100	99 72%
				すことです。あなたに	な	വില്‍ വിവിവിച്ചിരിക്കുന്നതിന് എന്നിവരിക്കുന്നതിന്റെ വിവിധ		100			0	0	100
VKORC1 673 (-1639)	ત્ત્વ	な	ন্ত		ਟ ਟ		0 % 0	91.7		22222	0 0	00	100
				ਦੀ ਇੱ	। ਡੇ ਟਿ			1 OC					100
			tota				ไฟ ไม	97.22	92.73		0	00	100	99.30%
				60	65			98.3		09	0)0		100
VKORCI 673 (-1639) GG	S	09	പ	09	60	0000000	0	100		60		0	100
			డు	60	60		ol-	100		09	0 0		1 00
			tota	08 I	179			10 66	98.08%	180		000	100	99.72%
otal for VKORC	3673 (-1639				428		র ব		98.06%	432	0		100	99.889
----------------------------------------------------------------------											Final Result*		I
Samples
Tested
Genotype	Tests Per
Site	Site	Genotype
Calls	Correct
Calls	ncorrect
Calls	Calls
No	% Correct
Calls	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Confidence	Correct
Calls	ncorrect
Calls	Calls
No	Correct
Calls
0/0	95% One-Sideo
Confidence
			432	429			99.3	------------------------------------------------------------------------------------------------------------------------------------------------------------------------------	432			100	Lower Limit 99.88% 99.88%
Total per Site		---------------------------------------------------
J	432	423			97.9	96.45% 99.31%	432			100
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------			432
10-4-4-4-4-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6-6	43 T			ਰੇ 8		432			100	99.88%
Total for Assa
The Call Company of Children And Children of Children Company of Children of			1296	1283		13	98.99	98.42%	296			100	99.96%

r

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7

Results after 10 minutes of samples

ت ج

ults after one repeat of samples repeat OK
1: no results - ip sense ligude des bourne of was buffer on one sample; correct test result achieved on secon
.

Second test result: Correct, shown on first page.

Note: No calibration sample was attached.

c Site 3: one sample had no call; correct test result achieved on second test

| Genotype | 2C9 | *2 | *3 | VKORCI
3673 (-16390 | #
Samples
Tested | Samples with
Genotype Calls
made by
INFINITIa | Samples with
Correct
Callsb | Samples with No
Calls | Samples with
Incorrect
Calls | First Time Run |
|----------|-------|----|----|------------------------|------------------------|--------------------------------------------------------|-----------------------------------|--------------------------|------------------------------------|----------------|
| *1/*2 | *1/*3 | | | AA | 36 | 34 | 34 | 2 | 0 | |
| *1/*1 | *1/*1 | | | GG | 36 | 36 | 36 | 0 | 0 | |
| *2/*2 | *1/*1 | | | GA | 36 | 35 | 35 | 1 | 0 | |
| *1/*1 | *3/*3 | | | GA | 36 | 35 | 35 | 1 | 0 | |

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le 3b Reproducibility Study Results by Sample

STIPULATION AND ORDER
FOR CONTINUANCE OF TRIAL
AND SETTING OF STATUS CONFERENCE

EXCELLENT SCHOOLS CALIFORNIA

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Total

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8

Drug Interference

Evaluation of potential interference from bilirubin, cholesterol, and heparin demonstrated that presence of these compounds in concentrations of 8mg/dl bilirubin, 70mg/dl cholesterol and 133v/dl heparin does not interfere with the INFINITI 2C9 & VKORC1 Multiplex Assay.

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.

Assay Interference

Running the INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin and the INFINITI Assay for Factor II & Factor V on the same instrument did not affect the results of the assays, i.e., the INFINITI 2C9 & VKORC 1 Multiplex Assay for Warfarin did not affect the results of the INFINITI Assay for Factor II & Factor V, and vise versa.

Reagent Stability

BioFilmChip Microaray:	12 months at RT (15-30°C)
Intellipac Reagent:	12 months Refrigerated (2-8°C)
Amplification Mix:	12 months Frozen (-10°C)

Conclusion

The above pre-clinical and clinical data support the safety and effectiveness of the INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin.

9

Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The logo is black and white and appears to be a simple, clean design.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 2 8 2008

Autogenomics, Inc Ms. Evelyn Lopez 2251 Rutherford Road Carlsbad, CA 92008

Re: K073014

Trade/Device Name: INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin Regulation Number: 21 CFR 862.3360 Regulation Name: Drug metabolizing enzyme genotyping system Regulatory Class: Class II Product Code: ODW, ODV, NSU Dated: October 23, 2007 Received: October 29, 2007

Dear Ms. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

10

Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Jean M. Coopes, M.S., D.V.M.

Jean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

11

Indications for Use

510(k) Number (if known):	K073014
Device Name:	INFINITI 2C9 &VKORC1 Multiplex Assay for Warfarin
Indications For Use:	The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is an in vitro diagnostic test for the detection and genotyping of the 2 and 3 CYP4502C9 genetic variants and the VKORC1 3673 (-1639) intronic variant in genomic deoxyribonucleic acid (DNA) obtained from EDTA-anticoagulated whole blood samples. The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is a qualitative assay for use in clinical laboratories upon prescription by the attending physician.
The INFINITI 2C9 & VKORC1 Multiplex Assay for Warfarin is indicated for use to identify individuals at risk for sensitivity to warfarin.

Prescription Use	X	AND/OR	Over-The-Counter Use
(Part 21 CFR 801 Subpart D)			(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)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

073016 510-1

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