ESENOR FII-FV-MTHFR GENOTYPING TEST, ESENOR FII-FV GENOTYPING TEST, ESENOR FII GENOTYPING by OSMETECH MOLECULAR DIAGNOSTICS

The eSensor® Thrombophila Risk Test is an in vitro diagnostic for the detection and genotyping of Factor II (Prothrombin) G20210A, Factor V (Factor V Leiden) G1691A and MTHFR (human 5, 10 methylenetetrahydrofolate reductase gene) C677T and A1298C mutations with suspected thrombophilia from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.

The eSensor® FII-FV Genotyping Test is an in vitro diagnostic for detection and genotyping of Factor II (Prothrombin) G20210A and Factor V (Factor V Leiden) G1691A mutations in patients with suspected thrombophilia from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.

The eSensor® FV Genotyping Test is an in vitro diagnostic for the detection and genotyping of a single point mutation (G to A at position 1691; also known as Factor V Leiden) of the human Factor V gene (FV; Coagulation Factor V gene) in patients with suspected thrombophilia from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.

The eSensor® FII Genotyping Test is an in vitro diagnostic for the detection and genotyping of a single point mutation (G to A at position 20210 of the human Factor II gene (FII; prothrombin gene) in patients with suspected thrombophilia, from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.

The eSensor® MTHFR Genotyping Test is an in vitro diagnostic for the detection and genotyping of point mutations (C to T at position 677) and (A to C at position 1298) of the human 5, 10 methylenetetrahydrofolate reductase gene (MTHFR) in patients with suspected thrombophilia, from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.

Device Description

The eSensor® Thrombophila Risk Tests on the eSensor® XT-8 System are in vitro diagnostic devices for performing hybridization and genotyping of multiple mutations and/or polymorphisms in an amplified DNA sample. A single-use, disposable test carridge is used to perform hybridization and genotyping. The cartridge contains an EEPROM chip which transmits the cartridge lot number, expiration date and protocol identity to the XT-8 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® Test cartidge, and the cartridge is inserted in the eSensor® XT-8 Instrument. The instrument controls the circulation of the cartridge 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 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 eSensor® XT-8 instrument analyzes the results and provides a report of the test results.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the eSensor® Thrombophila Risk Test, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary does not explicitly state "acceptance criteria" with numerical thresholds prior to presenting the results. However, the performance characteristics, particularly the "Method Comparison" results, implicitly serve as the primary demonstration of meeting performance expectations against a gold standard. For the reproducibility studies, "100% agreement" strongly implies this as an implicit acceptance criterion for internal consistency.

Performance Characteristic	Implicit Acceptance Criteria (Derived from results)	Reported Device Performance
Method Comparison (Agreement with DNA Sequencing)
FV Mutation (WT)	100% Agreement (or very high agreement >97%)	100.00% (Final results)
FV Mutation (HET)	100% Agreement (or very high agreement >97%)	100.00% (Final results)
FV Mutation (MUT)	100% Agreement (or very high agreement >70%)	100.00% (Final results)
FII Mutation (WT)	100% Agreement (or very high agreement >97%)	100.00% (Final results)
FII Mutation (HET)	100% Agreement (or very high agreement >89%)	100.00% (Final results)
FII Mutation (MUT)	100% Agreement (or very high agreement >68%)	100.00% (Final results)
MTHFR (C677T) Mutation (WT)	100% Agreement (or very high agreement >95%)	100.00% (Final results)
MTHFR (C677T) Mutation (HET)	100% Agreement (or very high agreement >97%)	100.00% (Final results)
MTHFR (C677T) Mutation (MUT)	100% Agreement (or very high agreement >90%)	100.00% (Final results)
MTHFR (A1298C) Mutation (WT)	100% Agreement (or very high agreement >95%)	100.00% (Final results)
MTHFR (A1298C) Mutation (HET)	100% Agreement (or very high agreement >97%)	100.00% (Final results)
MTHFR (A1298C) Mutation (MUT)	100% Agreement (or very high agreement >90%)	100.00% (Final results)
Reproducibility (Inter-laboratory, Inter-operator)	100% Agreement (First Pass Correct Calls and Final Correct Calls)	"All samples gave 100% correct calls."
Genomic DNA Extraction Reproducibility	100% Agreement (Correct Calls)	"All samples gave 100% correct calls when compared with DNA sequencing."
Lot to Lot Reproducibility	100% Agreement (Correct Calls)	"All samples gave 100% correct calls when compared with DNA sequencing."
Limit of Detection	100% Agreement at 10-500ng; High agreement at 1ng (e.g., >95%)	100% agreement at 10-500ng; 98% agreement at 1ng.

Note on "Implicit Acceptance Criteria": The document consistently reports 100% (final) agreement with DNA sequencing across all categories in the Method Comparison and 100% correct calls for reproducibility studies. This suggests that achieving perfect or near-perfect agreement with the gold standard (DNA sequencing) and internal consistency was the unstated "acceptance criterion" for these performance studies. The 95% LCB (Lower Confidence Bound) values provided in the method comparison table suggest that the statistical power was sufficient to be confident in these high agreement rates, even with sometimes smaller sample sizes for specific mutation types.

2. Sample Sizes Used for the Test Set and Data Provenance

Test Set Sample Size:
- Method Comparison: 219 gDNA samples.
- Reproducibility (Inter-laboratory, Inter-operator): 5 gDNA samples run in duplicate each day by each of 6 operators (2 operators per site across 3 sites) over 5 days = 5 x 2 x 3 x 5 = 150 test runs. The table states "Samples Tested: 50" per operator, totaling 300 tests. This implies a set of 5 gDNA samples were tested multiple times.
- Genomic DNA Extraction Reproducibility: 6 whole blood samples tested with 3 different extraction methods = 18 tests.
- Lot to Lot Reproducibility: 5 genomic DNA samples tested in duplicates using 3 different kit lots = 30 tests.
- Limit of Detection: 2 genomic DNA samples, each tested 20 times at 5 different concentrations = 2 x 20 x 5 = 200 tests.
Data Provenance: Not explicitly stated (e.g., country of origin). The document mentions "3 different sites and 1 internal site" for the reproducibility study, indicating multi-site testing within an unspecified geographic region. The "Method Comparison" study uses "gDNA samples extracted from whole blood," but the origin of these samples is not detailed. All data appears to be prospective in the sense of being generated specifically for these performance studies.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

Number of Experts: Not applicable in the traditional sense, as the ground truth was established by DNA sequencing, which is a laboratory method, not human expert consensus.
Qualifications of Experts: Not applicable. DNA sequencing is a technical standard.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. The ground truth (DNA sequencing) is considered the definitive standard. Any discrepancies between the eSensor® test and DNA sequencing would be considered an error by the eSensor® test, not a disagreement among experts requiring adjudication. The document mentions "Final Results" after "additional run for a single no-call" in the Lot to Lot study, suggesting a re-run policy for initial "no-calls" rather than adjudication. Similarly, in the method comparison, "Final Results" reflect cases where initial "no-calls" were resolved, making the "Final Agreement" 100%.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not done. This device is a molecular diagnostic test for genotyping, not an imaging diagnostic requiring interpretation by human readers. Therefore, the concept of human readers improving with AI assistance does not apply here.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done

Yes, a standalone performance study was done. This entire submission focuses on the performance of the eSensor® system (instrument + assay kits) as a standalone diagnostic device. The results are compared directly against DNA sequencing (the gold standard), and the system provides results without real-time human interpretation for genotype determination. Human intervention is limited to sample preparation, loading, and reviewing the automatically generated report.

7. The Type of Ground Truth Used

The type of ground truth used was DNA sequencing. This is explicitly stated across various sections, most notably under "Genomic DNA Extraction Reproducibility," "Lot to Lot Reproducibility," and "Method Comparison" where "All samples gave 100% correct calls when compared with DNA sequencing."

8. The Sample Size for the Training Set

The document does not explicitly state a separate "training set" or its sample size. Diagnostic kits like this, especially those based on hybridization and electrochemical detection principles for known mutations, are typically developed and optimized during an R&D phase, and then validated with the performance studies presented. There isn't typically a distinct "training set" in the same way machine learning algorithms have. The pre-market submission focuses on the validation of the finalized device.

9. How the Ground Truth for the Training Set Was Established

Since a separate "training set" is not explicitly mentioned or detailed, the method for establishing ground truth for such a set is also not described. If an internal training or optimization phase utilized samples, it can be inferred that DNA sequencing would have been the likely method for establishing their ground truth, consistent with the validation studies.

Summary

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510(k) SUMMARY: eSensor® Thrombophila Risk Test on XT-8 System

Preparation Date: March 24, 2010

Submitted By:

Osmetech Molecular Diagnostics 757 South Raymond Avenue Pasadena, CA 91105 USA Phone: 626 463-2000 Fax: 626 463-2012

K093974

Contacts:

Robert Dicheck, Vice President - Quality & Regulatory Affairs (Official Correspondent) Aviva Jacobs, Ph.D., Sr. Program Manager (Project Manager)

Proprietary Names and Classifications:

For the assay:

eSensor® FII-FV-MTHFR Genotyping Test (Kit) eSensor® Thrombophila Risk Test (Kit) eSensor® FII-FV Genotyping Test (Kit) eSensor® FII Genotyping Test (Kit) eSensor® FV Genotyping Test (Kit) eSensor® MTHFR Genotyping Test (Kit)

Regulation: 21CFR 864.7280 Panel: Hematology (81) Classification: II Product Codes: NPR, NPQ, OMM

For the instrument: eSensor® XT-8 Instrument (System) Regulation: 21CFR 862.2570 Panel: Clinical Chemistry (75) Classification: II Product Code: NSU - Instrument for Clinical Multiplex Test Systems

Common name:

For the assays: FII, Factor II, coagulation factor II, prothrombin, G20210A FV, Factor V, coagulation factor V, G1691A MTHFR, methylenetetrahydrofolate reductase Thrombosis Risk Genotyping Test Thrombophilia Risk Test

For the instrument. Instrument for Clinical Multiplex Test Systems

Intended uses:

This submission includes five separate product configurations, which were evaluated with the same data set.

The eSensor® Thrombophila Risk Test is an in vitro diagnostic for the detection and genotyping of Factor II

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(Prothrombin) G20210A, Factor V (Factor V Leiden) G1691A and MTHFR (human 5, 10 methylenetetrahydrofolate reductase gene) C677T and A1298C mutations with suspected thrombophilia from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.

The eSensor® FII-FV Genotyping Test is an in vitro diagnostic for detection and genotyping of Factor II (Prothrombin) G20210A and Factor V (Factor V Leiden) G1691A mutations in patients with suspected thrombophilia from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.
The eSensor® FV Genotyping Test is an in vitro diagnostic for the detection and genotyping of a single point mutation (G to A at position 1691; also known as Factor V Leiden) of the human Factor V gene (FV; Coagulation Factor V gene) in patients with suspected thrombophilia from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.
The eSensor® FII Genotyping Test is an in vitro diagnostic for the detection and genotyping of a single point mutation (G to A at position 20210 of the human Factor II gene (FII; prothrombin gene) in patients with suspected thrombophilia, from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.
The eSensor® MTHFR Genotyping Test is an in vitro diagnostic for the detection and genotyping of point mutations (C to T at position 677) and (A to C at position 1298) of the human 5, 10 methylenetetrahydrofolate reductase gene (MTHFR) in patients with suspected thrombophilia, from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.

Special conditions for use statement(s):

For Prescription Use Only

The eSensor® Thrombophila Risk Tests are in vitro diagnostic devices intended for genotyping either a single or multiple mutations or polymorphisms in an ample utilizing electrochemical detection technology, for use on the eSensor® XT-8 Instrument.

Predicate devices:

Verigene® F5 Nucleic Acid Test, Verigene® F2 Nucleic Acid Test, Verigene® MTHFR Nucleic Acid Test, K070597

eSensor® XT-8 Instrument, K073720 and K090901

Device Description:

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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 allelespecific ferrocene labels. The array also includes positive controls to confirm the hybridization reaction and detect non-specific signals.

Comparison to technological features of the predicate devices:

The following is a comparison of the Osmetech Molecular Diagnostics eSensor® Thrombophila Risk Test on the XT-8 System to the predicates

Characteristic	The Verigene F5 Nucleic Acid Test,The Verigene F2 Nucleic Acid Test,The Verigene MTHFR Nucleic Acid Test(Predicate: K070597)	eSensor® Thrombophilia Risk Test
Test type	Qualitative genetic test for single nucleotidepolymorphism detection	Same as predicate
Sample Type	Genomic DNA obtained from a human whole bloodsample	Same as predicate
Target of detection	Single-nucleotide polymorphism	Same as predicate
DNA extraction	Performed off-line	Same as predicate
Genes	Factor V Leiden,Factor II, Prothrombin,MTHFR	Same as predicate
Number of Locigenotyped	3(FV, FII and MTHFR C677T	4 (FV, FII and MTHFR C677T andA1298C)
Genotypingreaction location	Test cartridge	Same as predicate
Genotypingprinciple	Sandwich hybridization test	Same as predicate
Instrumentoperating system	The Verigene System consists of two instruments,the Verigene Processor and the Verigene Reader.	eSensor® Instrument Model XT-8 (K073720and K090901) is a single instrument withProcessor and Reader
Assay results	Assay signal results are interpreted by a softwareprogram and are assigned a result that is presented tothe end-user in a report format	Same as predicate

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Performance Characteristics:

Site to Site, Operator to Operator, Day, Run to Run and sample to sample reproducibility

The reproducibility study was performed over 5 non consecutive days at 3 different sites and 1 internal site). Each site performed the testing twice each day, using two different operators and the same testing materials. Each site had a separate XT-8 instrument. 5 gDNA samples containing a combination of samples which include heero and homozygotes for FV, MTHFR C677T and A 1298C, as well as FII heterozygotes were run in duplicate each day by each operator in order to assess intra-assay reproducibility

Summary of Inter-laboratory, Inter-operator, Reproducibility Results

Site	Operator	Samples Tested	First passCorrect calls	First passno- calls	Miscalls	Final Correctcalls	% Agreement
Site A	1	50	50	0	0	50	100%
Site A	2	50	50	0	0	50	100%
Site B	1	50	50	0	0	50	100%
Site B	2	50	49	1	0	50	100%
Site C	1	50	49	*1	0	50	100%
Site C	2	50	50	0	0	50	100%
All	All	300	298	2	0	300	100%
*This no-call was due to MTHER-A1298C low signal, FII, FV and MTHER-C677T were correctly called

Genomic DNA Extraction Reproducibility

A total of 6 whole blood samples of different genotypes were extraction methods and tested using the eSensor® Thrombophila Risk Test. The data were evaluated after first-pass results. There were zero no-call or miscalls. All samples gave 100% correct calls when compared with DNA sequencing. There was no impact of extraction method observed in this study. The following table summarizes the results of extraction reproducibility study.

Extraction Method	# Samples Tested	First pass correct calls	Final correct calls	Final Agreement %
A	6	6	6	100%
B	6	6	6	100%
C	6	6	6	100%
Total	18	18	18	100%

Lot to Lot Reproducibility

A total of 5 genomic DNA samples, containing positive calls for FII, FV, and MTHFR C677T and A1298C, were tested in duplicates using three different kit lots of the eSensor® Thromboohila Risk The first-pass results and following an additional run for a single no-call. All samples gave 100% correct calls when compared with DNA sequencing. There was a single first-pass no-call. but no impact of kit lot observed in this study. The following table summarizes the results of lot to lot reproducibility study.

LOT	Samples Tested	First pass correct calls	First pass		Final		Final correct calls	Final % Agreement
			No Calls	Mis-Calls	No Calls	Mis-Calls
1	20	20	0	0	0	0	20	100%
2	20	19	1	0	0	0	20	100%
3	20	20	0	0	0	0	20	100%
Total	60	59	*1	0	0	0	60	100%
*The single no-call was due to FII low signal. FV, MTHFR-C677T and MTHFR-A1298C were correctly called.

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Method Comparison

In a method comparison study, a total of 219 gDNA samples extracted from whole blood with A260-280 ratios of 1.0-2.9 were genotyped using the eSensor® Thrombophila Risk Test and DNA sequencing. All samples gave 100% agreement with DNA sequencing.

FV Mutation
	First Pass Results						Final Results
		eSensor® Results			1st PassNo-calls	Miscalls	%Agreement	95%LCB	eSensor® Results			FinalNo-calls	Miscalls	%Agreement	95%LCB
Results byDNASequencing	WT	181	0	0	1	0	99.45%	97.42%	182	0	0	0	0	100.00%	98.37%
	HET	0	27	0	1	0	96.43%	84.15%	0	28	0	0	0	100.00%	89.85%
	MUT	0	0	9	0	0	100.00%	71.69%	0	0	9	0	0	100.00%	71.69%
FII Mutation
	First Pass Results						Final Results
		eSensor® Results			1st PassNo-calls	Miscalls	%Agreement	95%LCB	eSensor® Results			FinalNo-calls	Miscalls	%Agreement	95%LCB
Results byDNASequencing	WT	183	0	0	1	0	99.46%	97.45%	184	0	0	0	0	100.00%	98.39%
	HET	0	27	0	0	0	100.00%	89.50%	0	27	0	0	0	100.00%	89.50%
	MUT	0	0	6	2	0	75.00%	40.03%	0	0	8	0	0	100.00%	68.77%
MTHFR (C677T) Mutation
	First Pass Results						Final Results
		eSensor® Results			1st PassNo-calls	Miscalls	%Agreement	95%LCB	eSensor® Results			FinalNo-calls	Miscalls	%Agreement	95%LCB
Results byDNASequencing	WT	68	0	0	0	0	100.00%	95.69%	68	0	0	0	0	100.00%	95.69%
	HET	0	118	0	2	0	98.33%	94.85%	0	120	0	0	0	100.00%	97.53%
	MUT	0	0	31	0	0	100.00%	90.79%	0	0	31	0	0	100.00%	90.79%
MTHFR (A1298C) Mutation
	First Pass Results						Final Results
		eSensor® Results			1st PassNo-calls	Miscalls	%Agreement	95%LCB	eSensor® Results			FinalNo-calls	Miscalls	%Agreement	95%LCB
Results byDNASequencing	WT	69	0	0	0	0	100.00%	95.75%	69	0	0	0	0	100.00%	95.75%
	HET	0	117	0	3	0	97.50%	93.67%	0	120	0	0	0	100.00%	97.53%
	MUT	0	0	30	0	0	100.00%	90.50%	0	0	30	0	0	100.00%	90.50%

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Other Characteristics of the eSensor® Thrombophila Risk Tests:

Characteristic	Result
Limit of detection	Two genomic DNA samples of different genotypes were extracted from whole blood stored in EDTA and serially diluted andtested 20 times each at input amounts of 0.1, 1, 10, 100, and 500 ng/PCR. using the eSensor® Thrombophila Risk Test. Up totwo additional run were performed for tests that gave a first pass no call result..All samples and replicates from 10ng-500ng input amount and above were called correctly with 100% agreement and 97.53%(95% LCB). At the limit of detection (1ng input amount), 39/40 replicates were correctly called which translates to 98%agreement 88.68% (95% LCB). The single no-call at the LOD was a positive cartridge control failure and not due to the inputgDNA amount.The lower detection limit was determined to be 1ng of purified DNA per reaction and the upper detection limit was determined to be 500 ng of purified DNA per reaction. The recommended range of DNA input amounts for the eSensor® ThrombophilaRisk Test is from 10 to 500 ng.
Interfering substances	Test performance was not affected by addition of the following substances to two whole blood samples of different genotypesprior to extraction• Heparin (3,000 U/L)• Cholesterol (250 mg/dL)• Bilurubin (30 mg /dL whole blood).• Hemoglobin (~20g /dL whole blood).• EDTA (at a concentration equivalent to 5-fold higher than that provided by a standard EDTA blood collection tube)
Interferingmutations and polymorphisms	The following interfering mutations were tested in 40 replicates alongside a Wild-Type control gDNA sample, with no effectobserved on, multiplex amplification of target gene sequences, or genotyping of FII-FV-MTHFR panel mutations by theeSensor® Thrombophila Risk Test:Non-Panel Mutation orPolymorphism Panel Mutation 1692A>C FV-1691G>A 1689G>A 1696A>G 20207A>C FII-20210G>A 20209C>T

Kit Stability:

eSensor® Thrombophila Risk Test kit components should be stored under the appropriate conditions until the expiration date printed on the label:

· PCR Box containing FII-FV-MTHFR PCR Mix and Taq Polymerase: Store at -20℃ in a designated pre-PCR area.
· Cartridges: Store at 10° to 25°C
· Genotyping Box containing Exonuclease, FIL-FV-MTHFR Signal 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:

· Cartidges can be stored for up to 30 days after opening the foil pouches. If stored, cartridges should be kept in their original foil pouch at room temperature in a dry place with the zip-loc closure sealed.
· Reagents can be thawed up to 5 times.
· Whole blood stored in EDTA can be stored for up to 4 weeks after collection of gDNA for use in the eSensor® Thrombophila Risk Tests.
· PCR product can be stored at 4°C or -20°C for up to 7 days.
· Exonuclease-digested PCR product can be stored store at 4℃ or -20℃ for up to 7 days.
· After combining the exonucleased PCR with hybridization reaction can be loaded on the caridge 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 safety and effectiveness of the eSensor® Thrombophila Risk Tests on the eSensor® XT-8 System, and demonstrate substantial equivalence to the predicate device.

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Image /page/6/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird symbol with three curved lines representing its wings or body. The bird is positioned to the right of a circular text element that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the circumference of the circle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

APR 22 2010

Osmetech Molecular Diagnostics c/o Mr. Robert S. Dicheck VP, Quality & Regulatory Affairs 757 South Raymond Avenue Pasadena, CA 91105

Re: K093974

Trade/Device Name:

Regulation Number:

Regulation Name:

Regulatory Class:

Product Code:

eSensor® Thrombophilia Risk Test eSensor® FII-FV Genotyping Test eSensor® FII Genotyping Test eSensor® FV Genotyping Test eSensor® MTHFR Genotyping Test 21 CFR §864.7280 Factor V Leiden DNA Mutation Detection Systems Class II NPQ, NPR, OMM, NSU April 1, 2010 April 5, 2010

Dear Mr. Dicheck:

Dated:

Received:

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 class II (Special Controls), 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.

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Page 2 - Mr. Robert S. Dicheck

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820). 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 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/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Reena Philip

$\to$
for

Maria M. Chan, Ph.D Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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K093974 510(k) Number (if known):

Device Name:

eSensor® Thrombophilia Risk Test

Indications for Use:

The eSensor® Thrombophilia Risk Test is an in vitro diagnostic for the detection and genotyping of Factor II (Prothrombin) G20210A, Factor V (Factor V Leiden) G1691A and MTHFR (human 5, 10 methylenetetrahydrofolate reductase gene) C677T and A1298C mutations in patients with suspected thrombophilia from isolated genomic DNA obtained from whole blood samples. The test is intended to be used on the eSensor® XT-8 System.

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

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

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

Reena Philip

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

510(k) K093974

{9}------------------------------------------------

510(k) Number (if known): K093974

Device Name:

eSensor® FV Genotyping Test

Indications for Use:

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

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

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

Reena Philip

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

510(k) K093974

{10}------------------------------------------------

K093974 510(k) Number (if known): _

Device Name:

eSensor® FII Genotyping Test

Indications for Use:

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

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

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

Leena Philip

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

510(k) K093974

{11}------------------------------------------------

510(k) Number (if known): Ko 93974

Device Name:

eSensor® FII-FV Genotyping Test

Indications for Use:

Prescription Use
X
(Part 21 CFR 801 Subpart D)
AND/OR

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

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

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

Leerie Philip
__
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K093974

{12}------------------------------------------------

510(k) Number (if known): 长09397 +

Device Name:

eSensor® MTHFR Genotyping Test

Indications for Use:

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (21 CFR 801 Subpart C)

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

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

Keene Philip

Division Sign-Off

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

510(k) K093974

Regulation Number and Section

§ 864.7280 Factor V Leiden DNA mutation detection systems.

(a)
Identification. Factor V Leiden deoxyribonucleic acid (DNA) mutation detection systems are devices that consist of different reagents and instruments which include polymerase chain reaction (PCR) primers, hybridization matrices, thermal cyclers, imagers, and software packages. The detection of the Factor V Leiden mutation aids in the diagnosis of patients with suspected thrombophilia.(b)
Classification. Class II (special controls). The special control is FDA's guidance entitled “Class II Special Controls Guidance Document: Factor V Leiden DNA Mutation Detection Systems.” (See § 864.1(d) for the availability of this guidance document.)