(199 days)
Not Found
Not Found
No
The description focuses on electrochemical detection and voltammetry for genotyping, with no mention of AI or ML algorithms for analysis or interpretation.
No.
The device is an in vitro diagnostic (IVD) test used to identify patients at risk for increased warfarin sensitivity by genotyping specific alleles, not for direct treatment or therapy.
Yes
The 'Intended Use / Indications for Use' section explicitly states, "The eSensor® Warfarin Sensitivity Test is an in vitro diagnostic for the detection and genotyping..." and "The eSensor® XT-8 Instrument is an in vitro diagnostic device intended for genotyping..."
No
The device description clearly outlines hardware components including the XT-8 Instrument, processing towers, and disposable test cartridges with EEPROM chips, which are integral to the device's function.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states in multiple places that the device is an "in vitro diagnostic":
- Intended Use / Indications for Use: "The eSensor® Warfarin Sensitivity Test is an in vitro diagnostic..." and "The eSensor® XT-8 Instrument is an in vitro diagnostic device..."
- Device Description: "The eSensor® XT-8 System is an in vitro diagnostic device..."
These statements clearly indicate that the device is intended for use in examining specimens derived from the human body to provide information for the diagnosis, prevention, or treatment of disease or for the assessment of health.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
ODW, ODV, NSU
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.
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
Rx only professional use within the confines of a licensed laboratory, as defined by the Clinical Laboratory Improvement Amendments (CLIA) of 1988.
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:
Sample Size: 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.
Study Type: Reproducibility (Inter-laboratory, Inter-Operator, Lot-to-Lot, Day-to-Day, Run-to-Run)
Key Results: All samples gave 100% agreement with DNA sequencing after additional testing of no-calls. There were 9 first-pass no-calls, with reasons identified. Final correct calls were 100% for each allele (2C92, 2C93, VKORC1) across all sites and operators.
Genomic DNA extraction reproducibility:
Sample Size: 7 whole blood samples of different genotypes, extracted in triplicate at 3 different sites.
Study Type: Reproducibility of genomic DNA extraction.
Key Results: All first-pass results were in 100% agreement with DNA sequencing.
Method comparison to bi-directional DNA sequencing:
Sample Size: 157 samples with A260/280 ratios of 1.2 to 2.3.
Study Type: Method comparison.
Key Results: All first-pass sample results (157/157) obtained with the eSensor® Warfarin Sensitivity Test agreed with the results obtained by DNA sequencing.
Limit of detection:
Sample Size: Two genomic DNA samples of different genotypes were serially diluted to 1000, 100, 10, 1, and 0.1, nanograms and assayed 20 times each.
Study Type: Limit of detection.
Key Results: The lower detection limit was determined to be 0.1 ng of purified DNA per reaction and the upper detection limit was determined to be 1000 ng of purified DNA per reaction. The recommended range of DNA input amounts for the eSensor® Warfarin Sensitivity Test is from 10 to 1000 ng.
Interfering substances:
Study Type: Interference testing.
Key Results: Test performance was not affected by addition of human serum albumin, Bilurubin, human immunoglobulin G, Triglycerides, Hemoglobin, Warfarin, Heparin sodium, and EDTA to whole blood samples.
Interfering mutations and polymorphisms:
Study Type: Interference testing for mutations/polymorphisms.
Key Results: Samples containing specific CYP450 2C9 polymorphisms (*4, *5, *6, *11, *14, *15, *16) were tested and found to give accurate results. Additional VKORC1 polymorphisms and rare mutations are not detected by the test.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Reproducibility:
For the overall reproducibility study (All Sites, All Operators):
- 2C9*2: 100% Agreement (95% LCB 98.5%)
- 2C9*3: 100% Agreement (95% LCB 98.5%)
- VKORC1: 100% Agreement (95% LCB 98.5%)
For Genomic DNA extraction reproducibility (Each site and allele):
- 100% Agreement (95% LCB 86.7%)
Method comparison to bi-directional DNA sequencing:
- Per-sample basis: 100% Agreement, 95% LCB 98.1%
- Per-SNP basis: 100% Agreement (471/471), 95% LCB 99.4%
- Specific Genotypes (Results, % Agreement, 95% LCB):
- 2C9 *1/1: 111, 100% (97.3%)
- 2C9 *1/2: 43, 100% (93.3%)
- 2C9*2/*2: 3, 100% (36.8%)
- 2C9 *1/1: 133, 100% (97.7%) (re-listed, likely a separate analysis context)
- 2C9 *1/*3: 22, 100% (87.3%)
- 2C9 *3/*3: 2, 100% (22.4%)
- VKORC1 G/G: 67, 100% (95.6%)
- VKORC1 G/A: 63, 100% (95.4%)
- VKORC1 AA: 27, 100% (89.5%)
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.
Nanosphere Verigene® Warfarin Metabolism Nucleic Acid Test and Verigene® System
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
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 | |
|---|---|
| Summary | |
| Preparation | |
| Date | July 15, 2008 |
| Submitted by | Osmetech Molecular Diagnostics |
| 757 South Raymond Ave. | |
| Pasadena, CA 91105 | |
| Phone: 626 463-2000 | |
| Fax: 626 463-2012 | |
| Contact | Robert Dicheck, Vice President of Quality & Regulatory Affairs (Official Correspondent) |
| Michael Reed, Ph.D., Director of Product Development & Project Manager | |
| Proprietary | |
| names and | |
| classifications | For the assay: |
| eSensor® Warfarin Sensitivity Test | |
| Regulations: 21CFR §862.3360 - Drug Metabolism Enzyme Genotyping Test | |
| 21CFR §864.7750 - Prothrombin Time Test | |
| Panels: 91 Toxicology & 81 Hematology | |
| Classification: II | |
| Product Codes: ODW Cytochrome P450 2C9 (CYP450 2C9) Drug Metabolizing Enzyme Genotyping | |
| System | |
| ODV Vitamin K epoxide reductase complex subunit 1 (VKORC1) Genotyping | |
| System | |
| For the instrument: | |
| eSensor® XT-8 System | |
| Regulation: 21CFR §862.2570 - Instrument for Clinical Multiplex Test Systems | |
| Panel: 75 Clinical Chemistry | |
| Classification: II | |
| Product Code: NSU Instrumentation for Clinical Multiplex Test Systems | |
| Common | |
| names | 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 *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. | |
| Special | |
| conditions for | |
| use | |
| statement(s) | 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. | |
| Predicate | |
| devices | Nanosphere Verigene® Warfarin Metabolism Nucleic Acid Test and Verigene® System |
1
| Device
descriptions | 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. | | |
| Comparison to
technological
features of the
predicate
device | The following is a comparison of the Osmetech Molecular Diagnostics eSensor® Warfarin Sensitivity Test
and XT-8 System to the Nanosphere, Inc. Verigene® Warfarin Metabolism Nucleic Acid Test and
Verigene® System. | | |
| | Characteristic | Verigene® Warfarin Metabolism
Nucleic Acid Test and Verigene®
System | eSensor® Warfarin Sensitivity
Test and XT-8 System |
| | 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 | Cytochrome P450 2C9 and VKORC1 | Same as predicate |
| | Number of Loci
genotyped | 3 | Same as predicate |
| | Genotyping reaction
location | Test cartridge | Same as predicate |
| | Genotyping principle | Sandwich hybridization test | Same as predicate |
| | User interface | Graphical user interface with touch
screen | Same as predicate |
| | Instrument operating
system | Random access compatible with
multiple simultaneous test types | Same as predicate |
| | Assay results | 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 | Same as predicate |
2
| Performance
characteristics | Reproducibility:
Site to Site, Operator to Operator, Lot to Lot, Day to Day and Run to Run reproducibility
A 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 | 2C92 | 50 | 42 | 8 | 50 | 0 | 100% (94.2%) |
| | | 2C93 | 50 | 42 | 8 | 50 | 0 | 100% (94.2%) |
| | | VKORC1 | 50 | 42 | 8 | 50 | 0 | 100% (94.2%) |
| 1 | 2 | 2C92 | 50 | 49 | 1 | 50 | 0 | 100% (94.2%) |
| | | 2C93 | 50 | 49 | 1 | 50 | 0 | 100% (94.2%) |
| | | VKORC1 | 50 | 49 | 1 | 50 | 0 | 100% (94.2%) |
| 2 | 3 | 2C92 | 50 | 50 | 0 | 50 | 0 | 100% (94.2%) |
| | | 2C93 | 50 | 50 | 0 | 50 | 0 | 100% (94.2%) |
| | | VKORC1 | 50 | 50 | 0 | 50 | 0 | 100% (94.2%) |
| 3 | 4 | 2C92 | 50 | 50 | 0 | 50 | 0 | 100% (94.2%) |
| | | 2C93 | 50 | 50 | 0 | 50 | 0 | 100% (94.2%) |
| | | VKORC1 | 50 | 50 | 0 | 50 | 0 | 100% (94.2%) |
| All | | 2C92 | 200 | 191 | 9 | 200 | 0 | 100% (98.5%) |
| All | | 2C93 | 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%) | |
3
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 | Incorrect Calls | No Calls | % Agreement (95% LCB) |
|---|---|---|---|---|---|---|
| 1 | 2C9*2 | 21 | 21 | 0 | 0 | 100% (86.7%) |
| 1 | 2C9*3 | 21 | 21 | 0 | 0 | 100% (86.7%) |
| 1 | VKORC1 | 21 | 21 | 0 | 0 | 100% (86.7%) |
| 2 | 2C9*2 | 21 | 21 | 0 | 0 | 100% (86.7%) |
| 2 | 2C9*3 | 21 | 21 | 0 | 0 | 100% (86.7%) |
| 2 | VKORC1 | 21 | 21 | 0 | 0 | 100% (86.7%) |
| 3 | 2C9*2 | 21 | 21 | 0 | 0 | 100% (86.7%) |
| 3 | 2C9*3 | 21 | 21 | 0 | 0 | 100% (86.7%) |
| 3 | VKORC1 | 21 | 21 | 0 | 0 | 100% (86.7%) |
Summary of Extraction Reproducibility Results (sorted by sample and genotype).
| Sample | Genotype | # Total
Tests | Correct
Calls | Incorrect
Calls | No Calls | %
Agreement |
|--------|----------------------|------------------|------------------|--------------------|----------|----------------|
| 01 | 2C9 *1/*1 VKORC1 G/G | 9 | 9 | 0 | 0 | 100% |
| 02 | 2C9 *1/*2 VKORC1 G/G | 9 | 9 | 0 | 0 | 100% |
| 03 | 2C9 *1/*3 VKORC1 G/A | 9 | 9 | 0 | 0 | 100% |
| 04 | 2C9 *1/*3 VKORC1 G/G | 9 | 9 | 0 | 0 | 100% |
| 05 | 2C9 *3/*3 VKORC1 G/G | 9 | 9 | 0 | 0 | 100% |
| 06 | 2C9 *2/*3 VKORC1 A/A | 9 | 9 | 0 | 0 | 100% |
| 07 | 2C9 *2/*3 VKORC1 A/A | 9 | 9 | 0 | 0 | 100% |
4
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:
| DNA
Sequencing
| Result | eSensor® Warfarin Sensitivity Test Result | 2C9 *1/1 | 2C9 *1/2 | 2C9*2/*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% | |
| DNA | ||||
| Sequencing | ||||
| Result | 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% | |
| DNA | ||||
| Sequencing | ||||
| Result | eSensor® Warfarin Sensitivity Test Result | VKORC1 | ||
| G/G | VKORC1 | |||
| G/A | VKORC1 | |||
| AA | ||||
| 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% |
5
| | Other
characteristics
of the
eSensor®
Warfarin
Sensitivity
Test | Characteristic | Result | |
|---------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| | | Limit of detection | Two genomic DNA samples of different genotypes were serially
diluted to 1000, 100, 10, 1, and 0.1, nanograms and assayed 20
times each using the eSensor® Warfarin Sensitivity Test. An
additional test was performed for tests that gave a first pass no call
result. All input amounts for both samples gave equivalent first-pass
and final performance. The lower detection limit was determined to
be 0.1 ng of purified DNA per reaction and the upper detection limit
was determined to be 1000 ng of purified DNA per reaction. The
recommended range of DNA input amounts for the eSensor®
Warfarin Sensitivity Test is from 10 to 1000 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:
• 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 whole
blood).
• 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 that
provided by a standard EDTA blood collection tube). | |
| | | Interfering mutations
and polymorphisms | Samples containing the following CYP450 2C9 polymorphisms have
been 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. These
additional polymorphisms and mutations are not detected by the
eSensor® Warfarin Sensitivity Test. | |
| Kit stability | eSensor® Warfarin Sensitivity Test kit components should be stored under the appropriate conditions until
the expiration date printed on the label: | | | |
| | • PCR Box containing Warfarin Sensitivity Test PCR Mix and Taq Polymerase: Store at -20°C in a
designated 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 be
kept 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. | | |
6
| • 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.
·
7
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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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® 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 whole blood samples preserved with EDTA, as an aid in the identification of patients at risk for increased warfarin sensitivity.
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)
A
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K073720