(120 days)
No
The device description focuses on standard molecular biology techniques (PCR, hybridization, voltammetry) for genotyping. There is no mention of AI or ML in the device description, intended use, or performance studies.
No
This device is an in vitro diagnostic (IVD) used for detecting and genotyping genetic mutations associated with thrombophilia. It provides diagnostic information rather than directly treating or preventing disease.
Yes
The "Intended Use / Indications for Use" section explicitly states repeatedly that these devices are "in vitro diagnostic" tests.
No
The device description clearly outlines the use of a physical, single-use, disposable test cartridge and an eSensor® XT-8 Instrument, which are hardware components essential to the device's function. The software is part of a larger system that includes hardware for sample processing, hybridization, detection, and analysis.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states for each of the listed tests: "The eSensor® [Test Name] is an in vitro diagnostic for the detection and genotyping of..."
Furthermore, the "Device Description" section also refers to the devices as "in vitro diagnostic devices".
N/A
Intended Use / Indications for Use
-
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.
Product codes (comma separated list FDA assigned to the subject device)
NPR, NPQ, OMM, NSU
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
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 Prescription Use Only
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Reproducibility Study:
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.
Results: All sites and operators showed 100% agreement in final correct calls (300/300 samples tested). Two first-pass no-calls were reported (one due to MTHFR-A1298C low signal, another due to FII low signal), but these were resolved to 100% agreement after additional runs/analysis.
Genomic DNA Extraction Reproducibility:
A total of 6 whole blood samples of different genotypes were evaluated with different extraction methods and tested using the eSensor® Thrombophila Risk Test.
Results: All samples (18 total across 3 methods) gave 100% correct calls when compared with DNA sequencing, with zero no-calls or miscalls. No impact of extraction method was observed.
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® Thrombophilia Risk Test.
Results: All samples (60 total) gave 100% correct calls when compared with DNA sequencing after an additional run for a single first-pass no-call. No impact of kit lot was observed.
Method Comparison:
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.
Results: All samples gave 100% agreement with DNA sequencing for FV, FII, MTHFR (C677T), and MTHFR (A1298C) mutations in the final results. There were some first-pass no-calls, which were resolved in the final results.
Limit of detection:
Two genomic DNA samples of different genotypes were extracted from whole blood stored in EDTA and serially diluted and tested 20 times each at input amounts of 0.1, 1, 10, 100, and 500 ng/PCR.
Results: 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 input gDNA 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® Thrombophila Risk Test is from 10 to 500 ng.
Interfering substances:
Test performance was not affected by addition of Heparin (3,000 U/L), Cholesterol (250 mg/dL), Bilirubin (30 mg /dL whole blood), Hemoglobin (~20g /dL whole blood), and EDTA (at a concentration equivalent to 5-fold higher than that provided by a standard EDTA blood collection tube) to two whole blood samples of different genotypes prior to extraction.
Interfering mutations and polymorphisms:
The following interfering mutations were tested in 40 replicates alongside a Wild-Type control gDNA sample, with no effect observed on, multiplex amplification of target gene sequences, or genotyping of FII-FV-MTHFR panel mutations by the eSensor® Thrombophila Risk Test: Non-Panel Mutation or Polymorphism Panel Mutation 1692A>C FV-1691G>A 1689G>A 1696A>G 20207A>C FII-20210G>A 20209C>T.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
First Pass Agreement (FV Mutation): WT 99.45%, HET 96.43%, MUT 100%. Final Agreement (FV Mutation): WT 100.00%, HET 100.00%, MUT 100.00%.
First Pass Agreement (FII Mutation): WT 99.46%, HET 100.00%, MUT 75.00%. Final Agreement (FII Mutation): WT 100.00%, HET 100.00%, MUT 100.00%.
First Pass Agreement (MTHFR C677T Mutation): WT 100.00%, HET 98.33%, MUT 100.00%. Final Agreement (MTHFR C677T Mutation): WT 100.00%, HET 100.00%, MUT 100.00%.
First Pass Agreement (MTHFR A1298C Mutation): WT 100.00%, HET 97.50%, MUT 100.00%. Final Agreement (MTHFR A1298C Mutation): WT 100.00%, HET 100.00%, MUT 100.00%.
LCB refers to Lower Confidence Bound of 95%.
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.
Reference Device(s):
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
§ 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.)
0
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
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
1
(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:
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
2
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.
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
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 nucleotide
polymorphism detection | Same as predicate |
| Sample Type | Genomic DNA obtained from a human whole blood
sample | 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 Loci
genotyped | 3(FV, FII and MTHFR C677T | 4 (FV, FII and MTHFR C677T and
A1298C) |
| Genotyping
reaction location | Test cartridge | Same as predicate |
| Genotyping
principle | Sandwich hybridization test | Same as predicate |
| Instrument
operating system | The Verigene System consists of two instruments,
the Verigene Processor and the Verigene Reader. | eSensor® Instrument Model XT-8 (K073720
and K090901) is a single instrument with
Processor and Reader |
| Assay results | Assay signal results are interpreted by a software
program and are assigned a result that is presented to
the end-user in a report format | Same as predicate |
3
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 pass
Correct calls | First pass
no- calls | Miscalls | Final Correct
calls | % 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 | First pass No Calls | Miscalls | Final correct calls | Final Agreement % |
|---|---|---|---|---|---|---|
| A | 6 | 6 | 0 | 0 | 6 | 100% |
| B | 6 | 6 | 0 | 0 | 6 | 100% |
| C | 6 | 6 | 0 | 0 | 6 | 100% |
| Total | 18 | 18 | 0 | 0 | 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. |
4
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 Pass | ||||||||||||||
| No-calls | Miscalls | % | |||||||||||||
| Agreement | 95% | ||||||||||||||
| LCB | eSensor® Results | Final | |||||||||||||
| No-calls | Miscalls | % | |||||||||||||
| Agreement | 95% | ||||||||||||||
| LCB | |||||||||||||||
| Results by | |||||||||||||||
| DNA | |||||||||||||||
| Sequencing | 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 Pass | ||||||||||||||
| No-calls | Miscalls | % | |||||||||||||
| Agreement | 95% | ||||||||||||||
| LCB | eSensor® Results | Final | |||||||||||||
| No-calls | Miscalls | % | |||||||||||||
| Agreement | 95% | ||||||||||||||
| LCB | |||||||||||||||
| Results by | |||||||||||||||
| DNA | |||||||||||||||
| Sequencing | 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 Pass | ||||||||||||||
| No-calls | Miscalls | % | |||||||||||||
| Agreement | 95% | ||||||||||||||
| LCB | eSensor® Results | Final | |||||||||||||
| No-calls | Miscalls | % | |||||||||||||
| Agreement | 95% | ||||||||||||||
| LCB | |||||||||||||||
| Results by | |||||||||||||||
| DNA | |||||||||||||||
| Sequencing | 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 Pass | ||||||||||||||
| No-calls | Miscalls | % | |||||||||||||
| Agreement | 95% | ||||||||||||||
| LCB | eSensor® Results | Final | |||||||||||||
| No-calls | Miscalls | % | |||||||||||||
| Agreement | 95% | ||||||||||||||
| LCB | |||||||||||||||
| Results by | |||||||||||||||
| DNA | |||||||||||||||
| Sequencing | 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% |
5
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 and | ||||||||||||
| tested 20 times each at input amounts of 0.1, 1, 10, 100, and 500 ng/PCR. using the eSensor® Thrombophila Risk Test. Up to | |||||||||||||
| two 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 input | |||||||||||||
| gDNA 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® Thrombophila | |||||||||||||
| Risk 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 genotypes | ||||||||||||
| prior 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) | |||||||||||||
| Interfering | |||||||||||||
| mutations and polymorphisms | The following interfering mutations were tested in 40 replicates alongside a Wild-Type control gDNA sample, with no effect | ||||||||||||
| observed on, multiplex amplification of target gene sequences, or genotyping of FII-FV-MTHFR panel mutations by the | |||||||||||||
| eSensor® Thrombophila Risk Test: | |||||||||||||
| Non-Panel Mutation or | |||||||||||||
| Polymorphism 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.
6
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.
7
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
8
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:
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.
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:
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.
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:
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.
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:
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.
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