The eSensor® Warfarin Sensitivity Test is an in vitro diagnostic for the detection and genotyping of the *2 and * 3 alleles of the cytochrome P450 (CYP450) 2C9 gene locus and the Vitamin K epoxide reductase C1 (VKORC1) gene promoter polymorphism (-1639G>A) from genomic DNA extracted from fresh whole blood samples preserved with EDTA, as an aid in the identification of patients at risk for increased warfarin sensitivity. The eSensor® Warfarin Sensitivity Test is for Rx only professional use within the confines of a licensed laboratory, as defined by the Clinical Laboratory Improvement Amendments (CLIA) of 1988.
The eSensor® XT-8 Instrument is an in vitro diagnostic device intended for genotyping multiple mutations or polymorphisms in an amplified DNA sample utilizing electrochemical detection technology.

Device Description

The eSensor® XT-8 System is an in vitro diagnostic device for performing hybridization and genotyping of multiple mutations and/or polymorphisms in an amplified DNA sample. The XT-8 Instrument is configured with one to three processing towers which perform up to 8 simultaneous tests per tower. The XT-8 System uses a single-use, disposable test cartridge to perform hybridization and genotyping in approximately 30 minutes per sample. The cartridge contains an EEPROM chip which transmits the cartridge lot number, expiration date and protocol identity to the instrument.
The analysis process for each sample consists of three steps: 1) Genomic DNA isolated from whole blood obtained using EDTA as anti-coagulant is combined with PCR Mix and Taq polymerase enzyme and is subjected to amplification of target sequences by PCR using a thermal cycler. 2) Amplified DNA is treated with exonuclease enzyme to generate single-stranded target DNA. 3) Single-stranded, amplified target DNA is mixed with hybridization and genotyping reagents and transferred to an eSensor® Warfarin Sensitivity Test cartridge, and the cartridge is inserted in the eSensor® XT-8 Instrument. The instrument controls the circulation of the sample inside the cartridge containing to allow hybridization at a controlled temperature, and then detects and genotypes the sample by voltammetry.
Genotyping of the test panel polymorphisms is achieved by a sandwich assay principle: 1) Each pair of electrodes contains a different synthetic oligonucleotide capture probe which is complementary to one of the target DNA fragments. 2) The hybridization reagents contain pairs of ferrocene-labeled synthetic oligonucleotide signal probes; one member of each pair is complementary to the major allele sequence of the target polymorphism, while the second member of the pair is complementary to the minor allele sequence. Each member of the probe pair has a ferrocene label with a different oxidation potential for each allele. 3) Single-stranded, amplified target DNA hybridizes to its specific capture probe, and in turn hybridizes to the allele-specific, ferrocene-labeled signal probe. 4) Each electrode of the array is analyzed by voltammetry; the target polymorphism is determined by the location of the electrode containing the capture probe, and the genotype is identified by the ratio of signals from the allele-specific ferrocene labels. The array also includes positive and negative controls to confirm the hybridization reaction and detect non-specific signals.
Upon completion of the test, the EEPROM chip on the cartridge contains information that prevents its re-use with a new sample. The instrument analyzes the results and provides a report of the test results. The operator removes the used cartridge from the slot of the XT-8 Instrument, and that slot is ready to accept a new test.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the eSensor® Warfarin Sensitivity Test and XT-8 System, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

Acceptance Criteria Category	Specific Metric (Implied)	Acceptance Criteria (Implied from 100% agreement)	Reported Device Performance	Comments
Reproducibility	Inter-laboratory, Inter-Operator, Lot-to-Lot, Day-to-Day, Run-to-Run	100% agreement with DNA sequencing after additional runs for no-calls	100% agreement (95% LCB > 94.2% for individual sites/alleles, > 98.5% overall) for final results	Initial no-calls (9 total) were attributed to cartridge manufacturing error (1) or operator error (8), all resolved with additional runs.
Genomic DNA Extraction Reproducibility	Across different extraction methods and sites	100% agreement with DNA sequencing for first-pass results	100% agreement (95% LCB > 86.7%) for first-pass results	No no-calls or incorrect calls during first-pass.
Method Comparison to Bi-directional DNA Sequencing	Agreement with DNA sequencing	100% agreement with DNA sequencing for first-pass sample results	100% agreement (95% LCB > 98.1% per sample, > 99.4% per SNP) for first-pass results	No no-calls or miscalls during first-pass.
Limit of Detection (LOD)	Lowest and highest detectable DNA concentration	0.1 ng to 1000 ng of purified DNA per reaction	Successfully genotyped at 0.1 ng to 1000 ng per reaction	Recommended input range: 10 to 1000 ng.
Interfering Substances	No impact on test performance	Test performance not affected by specified substances	No impact from human serum albumin, bilirubin, human immunoglobulin G, triglycerides, hemoglobin, warfarin, heparin sodium, or elevated EDTA.	Qualitative assessment based on accurate results.
Interfering Mutations and Polymorphisms	Accurate results despite certain known polymorphisms	Accurate results for specified CYP450 2C9 polymorphisms	Accurate results for CYP450 2C9 (4, 5, 6, 11, 14, 15, *16)	VKORC1 additional polymorphisms (other than -1639G>A) are not detected.

Study Details

Sample sizes used for the test set and the data provenance:
- Reproducibility Study Test Set:
  - Samples: 5 genomic DNA samples covering all possible genotypes for the three alleles (CYP2C92, CYP2C93, VKORC1).
  - Total Tests: 200 tests for each allele (CYP2C92, CYP2C93, VKORC1), for a grand total of 600 allele tests in the final analysis (5 samples * 4 operators/sites * 5 days * 2 runs per day = 200 tests per allele for an operator who performed 2 runs a day).
  - Data Provenance: Three sites were used: one internal (likely Osmetech Molecular Diagnostics) and two external. The country of origin is not specified, but given the submission is to the FDA, it is likely US-based or recognized for regulatory purposes. The study appears prospective, as it involves controlled testing of specific samples under varied conditions.
- Genomic DNA Extraction Reproducibility Test Set:
  - Samples: 7 whole blood samples of different genotypes.
  - Total Tests: 21 tests for each allele per site (7 samples * 3 replicates). With 3 sites, this totals 63 tests per allele, and 189 allele tests overall.
  - Data Provenance: Three different sites, using different commercially available extraction methods. Similar to the above, country of origin is not specified but likely US-based, and the study is prospective.
- Method Comparison Test Set:
  - Samples: 157 samples.
  - Total Tests: 157 samples tested on the eSensor device; 157 samples tested by DNA sequencing. On a per-SNP basis, this represents 471 data points (157 samples * 3 SNPs).
  - Data Provenance: Not explicitly stated, but implies collected samples for method comparison. The nature (retrospective/prospective) isn't directly stated, but typically, method comparison studies utilize a representative set of existing or collected samples in a controlled manner, making them essentially prospective for the purpose of the comparison.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth for all studies (reproducibility and method comparison) was established by DNA sequencing. The document does not specify the number of experts or their qualifications for interpreting the DNA sequencing results. DNA sequencing is generally considered a highly accurate gold standard for genotyping, and its interpretation often involves trained molecular biologists or geneticists, but no specific details are provided here.
Adjudication method for the test set:
- No formal adjudication method (like 2+1, 3+1 consensus) is explicitly mentioned for the test set.
- For the reproducibility study, "An additional run using the same kit lot and sample as for the first-pass test were performed for test that gave a no-call result." This implies a re-testing/re-run strategy for initial failures rather than human expert adjudication of output discrepancies. All no-calls were resolved to 100% agreement after additional runs.
- For the method comparison and extraction reproducibility, there were no initial no-calls or incorrect calls, so no adjudication or re-testing was necessary beyond the initial DNA sequencing ground truth.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No MRMC comparative effectiveness study was performed or described. This device is an in vitro diagnostic for genotyping, meaning it produces a direct genetic result, and there is no "human reader" analogue in the typical sense of interpreting imaging or complex clinical data where AI assistance would be measured. The output is a genotype, which is then used by medical professionals.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance studies (reproducibility, extraction reproducibility, and method comparison) represent the standalone performance of the eSensor® Warfarin Sensitivity Test and XT-8 System. The device analyzes DNA samples and outputs a genotype. While human operators perform PCR and load samples, the critical genotyping step and result interpretation are performed by the instrument's software ("Assay signal results are interpreted by a software program and are assigned a genotype that is presented to the end-user in a report format"). The 100% agreement with DNA sequencing demonstrates this algorithmic performance.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth used for all performance studies was bi-directional DNA sequencing. This is considered a highly reliable molecular diagnostic method.
The sample size for the training set:
- The document does not specify a separate "training set" or its size. As an in vitro diagnostic device, particularly for genetic testing, the development process generally involves analytical validation (like the studies described) rather than a machine learning training phase analogous to image analysis AI. The device's underlying "algorithm" is based on biochemical reactions and electrochemical detection, not a learned model from a dataset.
How the ground truth for the training set was established:
- Since no training set is explicitly mentioned in the context of machine learning, there's no ground truth establishment for such a set described. The "knowledge" or parameters for the device's operation would have been developed through biochemical and engineering principles, with validation done against known standards (DNA sequencing) as detailed in the performance studies.

Summary

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K073720

510(k) Summary

This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1900 and CFR 807.92

510(k) number
SummaryPreparationDate	July 15, 2008
Submitted by	Osmetech Molecular Diagnostics757 South Raymond Ave.Pasadena, CA 91105Phone: 626 463-2000Fax: 626 463-2012
Contact	Robert Dicheck, Vice President of Quality & Regulatory Affairs (Official Correspondent)Michael Reed, Ph.D., Director of Product Development & Project Manager
Proprietarynames andclassifications	For the assay:eSensor® Warfarin Sensitivity TestRegulations: 21CFR §862.3360 - Drug Metabolism Enzyme Genotyping Test21CFR §864.7750 - Prothrombin Time TestPanels: 91 Toxicology & 81 HematologyClassification: IIProduct Codes: ODW Cytochrome P450 2C9 (CYP450 2C9) Drug Metabolizing Enzyme GenotypingSystemODV Vitamin K epoxide reductase complex subunit 1 (VKORC1) GenotypingSystemFor the instrument:eSensor® XT-8 SystemRegulation: 21CFR §862.2570 - Instrument for Clinical Multiplex Test SystemsPanel: 75 Clinical ChemistryClassification: IIProduct Code: NSU Instrumentation for Clinical Multiplex Test Systems
Commonnames	For the Assay:Warfarin Sensitivity Test (CYP2C92, CYP2C93, VKORCI)For the Instrument.Bench-top molecular diagnostics workstation
Intended uses	• The eSensor® Warfarin Sensitivity Test is an in vitro diagnostic for the detection and genotyping of the 2and 3 alleles of the cytochrome P450 (CYP450) 2C9 gene locus and the Vitamin K epoxide reductaseC1 (VKORC1) gene promoter polymorphism (-1639G>A) from genomic DNA extracted from fresh wholeblood samples preserved with EDTA, as an aid in the identification of patients at risk for increasedwarfarin sensitivity. The eSensor® Warfarin Sensitivity Test is for Rx only professional use within theconfines of a licensed laboratory, as defined by the Clinical Laboratory Improvement Amendments (CLIA)of 1988.• The eSensor® XT-8 Instrument is an in vitro diagnostic device intended for genotyping multiple mutationsor polymorphisms in an amplified DNA sample utilizing electrochemical detection technology.
Specialconditions forusestatement(s)	The eSensor® Warfarin Sensitivity Test is for Rx only professional use within the confines of a licensedlaboratory, as defined by the Clinical Laboratory Improvement Amendments (CLIA) of 1988.
Predicatedevices	Nanosphere Verigene® Warfarin Metabolism Nucleic Acid Test and Verigene® System

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Devicedescriptions	The eSensor® XT-8 System is an in vitro diagnostic device for performing hybridization and genotyping ofmultiple mutations and/or polymorphisms in an amplified DNA sample. The XT-8 Instrument is configuredwith one to three processing towers which perform up to 8 simultaneous tests per tower. The XT-8 Systemuses a single-use, disposable test cartridge to perform hybridization and genotyping in approximately 30minutes per sample. The cartridge contains an EEPROM chip which transmits the cartridge lot number,expiration date and protocol identity to the instrument.
	The analysis process for each sample consists of three steps: 1) Genomic DNA isolated from whole bloodobtained using EDTA as anti-coagulant is combined with PCR Mix and Taq polymerase enzyme and issubjected to amplification of target sequences by PCR using a thermal cycler. 2) Amplified DNA is treatedwith exonuclease enzyme to generate single-stranded target DNA. 3) Single-stranded, amplified target DNAis mixed with hybridization and genotyping reagents and transferred to an eSensor® Warfarin SensitivityTest cartridge, and the cartridge is inserted in the eSensor® XT-8 Instrument. The instrument controls thecirculation of the sample inside the cartridge containing to allow hybridization at a controlled temperature,and then detects and genotypes the sample by voltammetry.
	Genotyping of the test panel polymorphisms is achieved by a sandwich assay principle: 1) Each pair ofelectrodes contains a different synthetic oligonucleotide capture probe which is complementary to one ofthe target DNA fragments. 2) The hybridization reagents contain pairs of ferrocene-labeled syntheticoligonucleotide signal probes; one member of each pair is complementary to the major allele sequence ofthe target polymorphism, while the second member of the pair is complementary to the minor allelesequence. Each member of the probe pair has a ferrocene label with a different oxidation potential for eachallele. 3) Single-stranded, amplified target DNA hybridizes to its specific capture probe, and in turnhybridizes to the allele-specific, ferrocene-labeled signal probe. 4) Each electrode of the array is analyzedby voltammetry; the target polymorphism is determined by the location of the electrode containing thecapture probe, and the genotype is identified by the ratio of signals from the allele-specific ferrocene labels.The array also includes positive and negative controls to confirm the hybridization reaction and detect non-specific signals.Upon completion of the test, the EEPROM chip on the cartridge contains information that prevents its re-use with a new sample. The instrument analyzes the results and provides a report of the test results. Theoperator removes the used cartridge from the slot of the XT-8 Instrument, and that slot is ready to accept anew test.
Comparison totechnologicalfeatures of thepredicatedevice	The following is a comparison of the Osmetech Molecular Diagnostics eSensor® Warfarin Sensitivity Testand XT-8 System to the Nanosphere, Inc. Verigene® Warfarin Metabolism Nucleic Acid Test andVerigene® System.
	Characteristic	Verigene® Warfarin MetabolismNucleic Acid Test and Verigene®System	eSensor® Warfarin SensitivityTest and XT-8 System
	Test type	Qualitative genetic test for singlenucleotide polymorphism detection	Same as predicate
	Sample Type	Genomic DNA obtained from a humanwhole blood sample	Same as predicate
	Target of detection	Single-nucleotide polymorphism	Same as predicate
	DNA extraction	Performed off-line	Same as predicate
	Genes	Cytochrome P450 2C9 and VKORC1	Same as predicate
	Number of Locigenotyped	3	Same as predicate
	Genotyping reactionlocation	Test cartridge	Same as predicate
	Genotyping principle	Sandwich hybridization test	Same as predicate
	User interface	Graphical user interface with touchscreen	Same as predicate
	Instrument operatingsystem	Random access compatible withmultiple simultaneous test types	Same as predicate
	Assay results	Assay signal results are interpreted by asoftware program and are assigned agenotype that is presented to the end-user in a report format	Same as predicate

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Performancecharacteristics	Reproducibility:Site to Site, Operator to Operator, Lot to Lot, Day to Day and Run to Run reproducibilityA reproducibility study was performed at three sites, two external and one internal. Five genomic DNA samples covering all possible genotypes for all three alleles in the Warfarin Sensitivity Test were tested in duplicate runs on a daily basis by the same operator for 5 days at 3 different sites. One site performed the same reproducibility testing twice each day, using two different operators and the same testing materials. Three kit lots were randomized throughout the study. An additional run using the same kit lot and sample as for the first-pass test were performed for test that gave a no-call result.The data were evaluated after first-pass results and following the additional run for no-calls. All samples gave 100% agreement with DNA sequencing. There were 9 first-pass no-calls: one was due to a cartridge manufacturing assembly error, and the remaining eight were due to operator error in set-up of the exonuclease reaction The following tables summarize the percent agreement between results obtained at each of the sites and DNA sequencing, before (first-pass) and after additional testing of no-calls (final):
Summary of Inter-laboratory and Inter-Operator Reproducibility Results
Site	Operator	Allele	Total tests	First-pass correct calls	First-pass no-calls	Final correct calls	Final incorrect calls	% Agreement (95% LCB)
1	1	2C9*2	50	42	8	50	0	100% (94.2%)
		2C9*3	50	42	8	50	0	100% (94.2%)
		VKORC1	50	42	8	50	0	100% (94.2%)
1	2	2C9*2	50	49	1	50	0	100% (94.2%)
		2C9*3	50	49	1	50	0	100% (94.2%)
		VKORC1	50	49	1	50	0	100% (94.2%)
2	3	2C9*2	50	50	0	50	0	100% (94.2%)
		2C9*3	50	50	0	50	0	100% (94.2%)
		VKORC1	50	50	0	50	0	100% (94.2%)
3	4	2C9*2	50	50	0	50	0	100% (94.2%)
		2C9*3	50	50	0	50	0	100% (94.2%)
		VKORC1	50	50	0	50	0	100% (94.2%)
All		2C9*2	200	191	9	200	0	100% (98.5%)
All		2C9*3	200	191	9	200	0	100% (98.5%)
All		VKORC1	200	191	9	200	0	100% (98.5%)
Summary of Reproducibility Results sorted by sample and genotype.
Sample	Genotype	Total Tests	First-pass correct calls	First-pass no-calls	Final correct calls	Final Incorrect calls	% Agreement (95% LCB)
01	2C9 1/1 VKORC1 G/G	40	37	3	40	0	100% (92.8%)
02	2C9 2/3 VKORC1 G/A	40	38	2	40	0	100% (92.8%)
03	2C9 2/2 VKORC1 G/G	40	39	1	40	0	100% (92.8%)
04	2C9 3/3 VKORC1 G/G	40	39	1	40	0	100% (92.8%)
05	2C9 1/3 VKORC1 A/A	40	38	2	40	0	100% (92.8%)

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Genomic DNA extraction reproducibility

Three different sites extracted 7 whole blood samples of different genotypes in triplicate and tested them using the eSensor® Warfarin Sensitivity Test. Each site used a different commercially available extraction method, which yielded DNA with A260/280 ratios of 1.7 to 3.3. First pass results were in 100% agreement with DNA sequencing, as shown in the following tables:

Summary of Inter-laboratory Extraction Reproducibility Results

Site	Allele	# Total Tests	Correct Calls	% Agreement (95% LCB)
1	2C9*2	21	21	100% (86.7%)
1	2C9*3	21	21	100% (86.7%)
1	VKORC1	21	21	100% (86.7%)
2	2C9*2	21	21	100% (86.7%)
2	2C9*3	21	21	100% (86.7%)
2	VKORC1	21	21	100% (86.7%)
3	2C9*2	21	21	100% (86.7%)
3	2C9*3	21	21	100% (86.7%)
3	VKORC1	21	21	100% (86.7%)

Summary of Extraction Reproducibility Results (sorted by sample and genotype).

Sample	Genotype	# TotalTests	CorrectCalls	%Agreement
01	2C9 1/1 VKORC1 G/G	9	9	100%
02	2C9 1/2 VKORC1 G/G	9	9	100%
03	2C9 1/3 VKORC1 G/A	9	9	100%
04	2C9 1/3 VKORC1 G/G	9	9	100%
05	2C9 3/3 VKORC1 G/G	9	9	100%
06	2C9 2/3 VKORC1 A/A	9	9	100%
07	2C9 2/3 VKORC1 A/A	9	9	100%

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Method comparison to bi-directional DNA sequencing:

In a method comparison study, a total of 157 samples with A260/280 ratios of 1.2 to 2.3 were genotyped using the eSensor® Warfarin Sensitivity Test and DNA Sequencing. All first-pass sample results (157/157) obtained with the eSensor® Warfarin Sensitivity Test agreed with the results obtained by DNA sequencing. The 95% lower confidence bound on a per-sample basis was 98.1%, and 99.4% on a per-SNP basis (471/471). The following table summarizes the results of the method comparison study:

DNASequencingResult	eSensor® Warfarin Sensitivity Test Result	2C9 *1/1	2C9 *1/2	2C92/2
Result		111	43	3
No-Calls		0	0	0
Miscalls		0	0	0
%Agreement		100%	100%	100%
95% LCB		97.3%	93.3%	36.8%
DNASequencingResult	eSensor® Warfarin Sensitivity Test Result	2C9 *1/1	2C9 1/3	2C9 3/3
Result		133	22	2
No-Calls		0	0	0
Miscalls		0	0	0
%Agreement		100%	100%	100%
95% LCB		97.7%	87.3%	22.4%
DNASequencingResult	eSensor® Warfarin Sensitivity Test Result	VKORC1G/G	VKORC1G/A	VKORC1AA
Result		67	63	27
No-Calls		0	0	0
Miscalls		0	0	0
%Agreement		100%	100%	100%
95% LCB		95.6%	95.4%	89.5%

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	Othercharacteristicsof theeSensor®WarfarinSensitivityTest	Characteristic	Result
		Limit of detection	Two genomic DNA samples of different genotypes were seriallydiluted to 1000, 100, 10, 1, and 0.1, nanograms and assayed 20times each using the eSensor® Warfarin Sensitivity Test. Anadditional test was performed for tests that gave a first pass no callresult. All input amounts for both samples gave equivalent first-passand final performance. The lower detection limit was determined tobe 0.1 ng of purified DNA per reaction and the upper detection limitwas determined to be 1000 ng of purified DNA per reaction. Therecommended range of DNA input amounts for the eSensor®Warfarin Sensitivity Test is from 10 to 1000 ng..
		Interferingsubstances	Test performance was not affected by addition of the followingsubstances to two whole blood samples of different genotypes priorto extraction:• Human serum albumin (3 g added/dL whole blood).• Bilurubin (50 µg added/mL whole blood).• Human immunoglobulin G (3 g added/dL whole blood).• Triglycerides (3 g added/dL whole blood).• Hemoglobin (20 g added as purified red blood cells/dL wholeblood).• Warfarin (32.5 µM added to whole blood).• Heparin sodium (3,000 U/L added to whole blood).• EDTA (at a concentration equivalent to 5-fold higher than thatprovided by a standard EDTA blood collection tube).
		Interfering mutationsand polymorphisms	Samples containing the following CYP450 2C9 polymorphisms havebeen tested and found to give accurate results in the eSensor®Warfarin Sensitivity Test:• 1076T>C (4)• 1080C>G (5)• 818delA (6)• 1003C>T (11)• 374G>A (14)• 485C>A (15)• 895A>G (*16).In the VKORC1 gene, additional polymorphisms other than-1639G>A, as well as rare mutations have been observed. Theseadditional polymorphisms and mutations are not detected by theeSensor® Warfarin Sensitivity Test.
Kit stability	eSensor® Warfarin Sensitivity Test kit components should be stored under the appropriate conditions untilthe expiration date printed on the label:
	• PCR Box containing Warfarin Sensitivity Test PCR Mix and Taq Polymerase: Store at -20°C in adesignated pre-PCR area.
	• Cartridges: Store at 10° to 25°C
	• Genotyping Box containing Exonuclease, Warfarin Sensitivity Test Signal Buffer, XT-Buffer 1 and XT-Buffer 2: Store at -20°C in a designated post-PCR area.
	In-process stability has been established for the following components, working reagents and samples:
	• Cartridges can be stored for up to 14 days after opening the foil pouches. If stored, cartridges should bekept in their original foil pouch at room temperature in a dry place with the zip-loc closure sealed.
	• Once open, reagents can be stored at -20°C for up to 30 days.
	• Reagents can be thawed up to 3 times.
	• Whole blood stored in EDTA can be stored for up to 4 weeks after collection prior to extraction of gDNA
		for use in the eSensor® Warfarin Sensitivity Test.
		• PCR product can be stored at 4°C or -20°C for up to 7 days.

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	• Exonuclease-digested PCR product can be stored store at 4°C or -20°C for up to 7 days.
	• After combining the exonuclease-digested PCR with hybridization reagents, the hybridization reaction can be loaded on the cartridge and held at ambient temperature for up to 8 hours before initiating hybridization of the cartridge on the XT-8 instrument.
Conclusion	The above internal and clinical test results support the safety and effectiveness of the eSensor® Warfarin Sensitivity Test and the eSensor® XT-8 System, and demonstrate substantial equivalence to the predicate device.

eSensor® is a registered trademark of Osmetech and its subsidiaries.

Verigene® is a registered trademark of Nanosphere, Inc.

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Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Osmetech Molecular Diagnostics c/o Mr. Robert Dicheck Vice President of Quality & Regularoty Affairs 757 South Raymond Avenue Pasadena, CA 91105

JUL 1 7 2008

K073720 Re: Trade Name: eSensor® Warfarin Sensitivity Test, eSensor® XT-8 System Regulation Number: 21 CFR 862.3360 Regulation Name: Drug Metabolism Enzyme Genotyping Test Regulatory Class: Class II Product Codes: ODW_ODV_ NSU

Dated: May 22, 2008 Received: May 27, 2008

Dear Mr. Dicheck:

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).

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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) 276-31 50 or at its finternet attress at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Jean M. Coopes, M.S., D.v.M.

Yean 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

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Indications for Use

K013720 510(k) Number (if known):

Device Name: eSensor® Warfarin Sensitivity Test and XT-8 System

Indications For Use:

The eSensor® XT-8 Instrument is an in vitro diagnostic device intended for genotyping multiple mutations or polymorphisms in an amplified DNA sample utilizing electrochemical detection technology.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K073720

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.