(255 days)
The eSensor® Warfarin Sensitivity Saliva Test is an in vitro diagnostic test 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 of human saliva samples collected using the Oragene® Dx Device, as an aid in the identification of patients at risk for increased warfarin sensitivity.
The eSensor® Warfarin Sensitivity Saliva Test is a multiplex microarray-based genotyping test system. It is based on the principles of competitive DNA hybridization using a sandwich assay format, wherein a single-stranded target binds concurrently to sequence-specific solution-phase signal probe and solid-phase electrode-bound capture probe. The test employs polymerase chain reaction amplification, exonuclease digestion and hybridization of target DNA. In the process, the double stranded PCR amplicons are digested with exonuclease to generate single stranded DNA suitable for hybridization. Hybridization occurs in the eSensor XT-8 Cartridge (described below) where the singlestranded target DNA is mixed with a hybridization solution containing labeled signal probes.
During hybridization, the target DNA binds to a complementary, single-stranded capture probe immobilized on the working electrode surface. Single-stranded signal probes (labeled with electrochemically active ferrocenes) bind to the target adjacent to the capture probe. When inserted into the eSensor XT-8 instrument (described below), simultaneous hybridization of target to signal probes and capture probe is detected by alternating current voltammetry (ACV). Each pair of working electrodes on the array contains a different capture probe, and sequential analysis of each electrode allows genotyping of multiple mutations or polymorphisms.
The Assay Cartridge (eSensor XT-8 Cartridge): The eSensor XT-8 cartridge device consists of a printed circuit board (PCB) with a multi-layer laminate and a plastic cover that forms a hybridization chamber has a volume of approximately 140 µl. The cartridge consists of a diaphragm pump and check valves (microfluidic components) that circulate the hybridization solution in the hybridization chamber when inserted into the eSensor XT-8 instrument. The PCB chip consists of an array of 72 gold-plated working electrodes, a silver/silver chloride reference electrode, and two gold-plated auxiliary electrodes. Each working electrode has a connector contact pad on the opposite side of the chip for electrical connection to the eSensor XT-8 instrument. Each electrode is modified with a multicomponent, self-assembled monolayer that includes presvnthesized oligonucleotide capture probes specific for each polymorphic site on the test panel and insulator molecules. The cartridge also contains an electrically erasable programmable read-only memory component (EEPROM) that stores information related to the cartridge (e.g., assay identifier, cartridge lot number, and expiration date).
The eSensor XT-8 Instrument (Same as cleared under K073720): The eSensor XT-8 is a clinical multiplex instrument that has a modular design consisting of a base module and one, two, or three cartridge-processing towers containing 8, 16, or 24 cartridge slots, respectively. The cartridge slots operate independently of each other. Any number of cartridges can be loaded at one time, and the remaining slots are available for use while the instrument is running. The base module controls each processing tower, provides power, and stores and analyzes data. The base module includes the user interface, and a 15-in. portrait-orientation display and touch panel. The instrument is designed to be operated solely with the touch screen interface. Entering patient accession numbers and reagent lot codes can be performed by the bar code scanner, the touch screen, or uploading a text file from a USB memory stick. Each processing tower consists of eight cartridge modules, each containing a cartridge connector, a precision-controlled heater, an air pump, and electronics. The air pumps drive the diaphragm pump and valve system in the cartridge, eliminating fluid contact between the instrument and the cartridge. The pneumatic pumping enables recirculation of the hybridization solution allowing the target DNA and the signal probes to hybridize with the complementary capture probes on the electrodes. The diaphragm pump in the cartridge is connected to a pneumatic source from the eSensor XT-8 instrument and provides unidirectional pumping of the hybridization mixture through the microfluidic channel during hybridization. Using microfluidic technology to circulate the hybridization solution minimizes the unstirred boundary layer at the electrode surface and continuously replenishes the volume above the electrode that has been depleted of complementary targets and signal probes. The XT-8 instrument provides electrochemical detection of bound signal probes by ACV and subsequent data analysis and test report generating functions. All hybridization, ACV scanning and analysis parameters are defined by a scanning protocol loaded into the XT-8 Software, and then specified for use by the EEPROM on each cartridge.
The Assay Kit: The Warfarin Sensitivity Saliva Test consists of the test cartridge and the following components: 1) PCR REAGENTS consisting of: PCR Mix [PCR buffer containing primers and dNTP mixture (dCTP, dGTP, dATP, and dUTP)], MgCl2 thermostable DNA polymerase (Taq Polymerase ); and 2 GENOTYPING REAGENTS consisting of: lambda exonuclease, signal probes and hybridization buffer ingredients (Buffer-1 and Buffer-2).
Here's a breakdown of the acceptance criteria and the study details for the eSensor® Warfarin Sensitivity Saliva Test, based on the provided document:
Acceptance Criteria and Device Performance
The acceptance criteria are implied by the comparison to DNA sequencing, which is considered the gold standard for genotyping. The device performance is reported as agreement percentages with DNA sequencing.
| Characteristic | Acceptance Criteria (Implied) | Reported Device Performance (After Retest) |
|---|---|---|
| *CYP450 2C9 2 Allele Genotyping | High agreement with DNA sequencing | |
| 2C9 wt/wt Agreement | - | 100.0% (95% LCB: 98.7%) |
| 2C9 wt/*2 Agreement | - | 98.6% (95% LCB: 93.4%) |
| 2C9 *2/*2 Agreement | - | 100.0% (95% LCB: 71.7%) |
| *CYP450 2C9 3 Allele Genotyping | High agreement with DNA sequencing | |
| 2C9 wt/wt Agreement | - | 99.3% (95% LCB: 97.8%) |
| 2C9 wt/*3 Agreement | - | 100.0% (95% LCB: 91.6%) |
| 2C9 *3/*3 Agreement | - | 100.0% (95% LCB: 36.8%) |
| VKORC1 Genotyping | High agreement with DNA sequencing | |
| VKORC1 G/G Agreement | - | 100.0% (95% LCB: 97.6%) |
| VKORC1 G/A Agreement | - | 100.0% (95% LCB: 97.8%) |
| VKORC1 A/A Agreement | - | 100.0% (95% LCB: 95.3%) |
| Interference Study | 100% agreement with DNA sequencing | |
| Endogenous Interfering Substances (Control, Amylase, Hemoglobin, IgA, Total Protein) | 100% agreement | 100% agreement for all substances |
| Exogenous Interfering Substances (Eating, Drinking, Chewing Gum, Mouthwash, Smoking) | 100% agreement | 100% agreement for all activities |
Note: The document implies acceptance criteria by comparing the device's performance to DNA sequencing, which is implicitly considered the standard for accuracy. Specific numeric thresholds for "acceptance" are not explicitly stated, but the high agreement percentages (mostly 100%) and the lower bounds of the 95% confidence intervals (LCB) suggest a requirement for high concordance.
Study Information
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size: A total of 316 gDNA samples were extracted from saliva specimens for the method comparison study.
- Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. It uses "saliva specimen" without further context on donor recruitment or source.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts:
- Experts: Not applicable. The "ground truth" for the genotyping results was established by DNA sequencing, not by human experts.
- Qualifications: Not applicable.
4. Adjudication Method for the Test Set:
- Adjudication Method: Not applicable in the traditional sense of human consensus. The reference method (ground truth) was DNA sequencing. The study reports "No-Calls" and "Miscalls" by the eSensor® device when compared to DNA sequencing. The "After Retest" results suggest that initial "No-Calls" were re-evaluated and resolved, leading to higher agreement.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- MRMC Study: No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) for genotyping, which is an automated process, not an imaging device requiring human interpretation alongside AI.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Standalone Performance: Yes, the performance reported is essentially a standalone (algorithm only) performance. The eSensor® Warfarin Sensitivity Saliva Test is an automated system that generates results which are then compared to DNA sequencing, without human-in-the-loop interpretation being part of the primary performance evaluation.
7. The Type of Ground Truth Used:
- Ground Truth Type: DNA sequencing (referred to as "bidirectional DNA sequencing" or "DNA Sequencing Result"). This is considered a gold standard for genetic polymorphism detection.
8. The Sample Size for the Training Set:
- Training Set Sample Size: The document does not specify a separate training set. For IVD devices, especially those based on established molecular biology principles, the "training" (development) often involves optimizing reagents and protocols, rather than machine learning algorithm training with distinct datasets. The method comparison study appears to be the primary validation of the device's performance against a reference method.
9. How the Ground Truth for the Training Set was Established:
- Training Set Ground Truth: As no explicit training set is mentioned in the context of machine learning, this question is not directly applicable. For the performance validation, as stated above, DNA sequencing was used as the ground truth.
{0}------------------------------------------------
DEC - 2 2011 K110786
510(k) SUMMARY: eSensor® Warfarin Sensitivity Saliva Test on XT-8 System
Preparation Date: October 24, 2011
Submitted By: Clinical Micro Sensor dba GenMark 5964 La Place Court, Suite100 Carlsbad, CA 92008 USA Phone: 760-448-4300 Fax: 760-683-6821
Contacts:
John Riolo, Vice President - Quality & Regulatory Affairs (Official Correspondent)
Proprietary Names and Classifications:
For the assay: eSensor® Warfarin Sensitivity Saliva Test (Kit)
Regulation: 21CFR 864.7280 Panel: Hematology (81) Classification: Class II Product Codes: CYTOCHROME P450 2C9 (CYP450 2C9) DRUG METABOLIZING ENZYME GENOTYPING SYSTEM (ODW) and VITAMIN K EPOXIDE REDUCTASE COMPLEX SUBUNIT ONE (VKORC1) GENOTYPING SYSTEM (ODV)
For the instrument: eSensor® XT-8 Instrument (System) Regulation: 21CFR 862.2570 Panel: Clinical Chemistry (75) Classification: Class II Product Code: NSU - Instrument for Clinical Multiplex Test Systems
Common name:
Warfarin Sensitivity Saliva CYP450 2C9 *2 and CYP450 2C9 *3 alleles and VKORC1 Genotyping
Intended use:
The eSensor® Warfarin Sensitivity Saliva Test is an in vitro diagnostic test 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 of human saliva samples collected using the Oragene® Dx Device, as an aid in the identification of patients at risk for increased warfarin sensitivity.
Special conditions for use statement(s):
The eSensor® Warfarin Sensitivity Saliva Test can provide information to the physician and lab director on the genotype and allele designation of the three (3) polymorphisms stated in the intended use. However, determination of the therapeutic strategy and treatment dose for Warfarin will depend on multiple additional factors and are beyond the scope of the eSensor® Warfarin Sensitivity
{1}------------------------------------------------
Saliva Test Report and Package Insert.
The eSensor® Warfarin Saliva Sensitivity Test is for in vitro diagnostic use within a licensed laboratory, as defined by the Clinical Laboratory Improvement Amendments (CLIA) of 1988.
Predicate devices:
K073720 eSensor Warfarin Sensitivity Test eSensor XT-8 System
Device Description:
The eSensor® Warfarin Sensitivity Saliva Test is a multiplex microarray-based genotyping test system. It is based on the principles of competitive DNA hybridization using a sandwich assay format, wherein a single-stranded target binds concurrently to sequence-specific solution-phase signal probe and solid-phase electrode-bound capture probe. The test employs polymerase chain reaction amplification, exonuclease digestion and hybridization of target DNA. In the process, the double stranded PCR amplicons are digested with exonuclease to generate single stranded DNA suitable for hybridization. Hybridization occurs in the eSensor XT-8 Cartridge (described below) where the singlestranded target DNA is mixed with a hybridization solution containing labeled signal probes.
During hybridization, the target DNA binds to a complementary, single-stranded capture probe immobilized on the working electrode surface. Single-stranded signal probes (labeled with electrochemically active ferrocenes) bind to the target adjacent to the capture probe. When inserted into the eSensor XT-8 instrument (described below), simultaneous hybridization of target to signal probes and capture probe is detected by alternating current voltammetry (ACV). Each pair of working electrodes on the array contains a different capture probe, and sequential analysis of each electrode allows genotyping of multiple mutations or polymorphisms.
The Assay Cartridge (eSensor XT-8 Cartridge)
The eSensor XT-8 cartridge device consists of a printed circuit board (PCB) with a multi-layer laminate and a plastic cover that forms a hybridization chamber has a volume of approximately 140 µl. The cartridge consists of a diaphragm pump and check valves (microfluidic components) that circulate the hybridization solution in the hybridization chamber when inserted into the eSensor XT-8 instrument. The PCB chip consists of an array of 72 gold-plated working electrodes, a silver/silver chloride reference electrode, and two gold-plated auxiliary electrodes. Each working electrode has a connector contact pad on the opposite side of the chip for electrical connection to the eSensor XT-8 instrument. Each electrode is modified with a multicomponent, self-assembled monolayer that includes presvnthesized oligonucleotide capture probes specific for each polymorphic site on the test panel and insulator molecules. The cartridge also contains an electrically erasable programmable read-only memory component (EEPROM) that stores information related to the cartridge (e.g., assay identifier, cartridge lot number, and expiration date).
The eSensor XT-8 Instrument (Same as cleared under K073720)
The eSensor XT-8 is a clinical multiplex instrument that has a modular design consisting of a base module and one, two, or three cartridge-processing towers containing 8, 16, or 24 cartridge slots, respectively. The cartridge slots operate independently of each other. Any number of cartridges can be loaded at one time, and the remaining slots are available for use while the instrument is running.
{2}------------------------------------------------
The base module controls each processing tower, provides power, and stores and analyzes data. The base module includes the user interface, and a 15-in. portrait-orientation display and touch panel. The instrument is designed to be operated solely with the touch screen interface. Entering patient accession numbers and reagent lot codes can be performed by the bar code scanner, the touch screen, or uploading a text file from a USB memory stick.
Each processing tower consists of eight cartridge modules, each containing a cartridge connector, a precision-controlled heater, an air pump, and electronics. The air pumps drive the diaphragm pump and valve system in the cartridge, eliminating fluid contact between the instrument and the cartridge. The pneumatic pumping enables recirculation of the hybridization solution allowing the target DNA and the signal probes to hybridize with the complementary capture probes on the electrodes. The diaphragm pump in the cartridge is connected to a pneumatic source from the eSensor XT-8 instrument and provides unidirectional pumping of the hybridization mixture through the microfluidic channel during hybridization. Using microfluidic technology to circulate the hybridization solution minimizes the unstirred boundary layer at the electrode surface and continuously replenishes the volume above the electrode that has been depleted of complementary targets and signal probes.
The XT-8 instrument provides electrochemical detection of bound signal probes by ACV and subsequent data analysis and test report generating functions. All hybridization, ACV scanning and analysis parameters are defined by a scanning protocol loaded into the XT-8 Software, and then specified for use by the EEPROM on each cartridge.
The Assay Kit
The Warfarin Sensitivity Saliva Test consists of the test cartridge and the following components: 1) PCR REAGENTS consisting of: PCR Mix [PCR buffer containing primers and dNTP mixture (dCTP, dGTP, dATP, and dUTP)], MgCl2 thermostable DNA polymerase (Taq Polymerase ); and 2 GENOTYPING REAGENTS consisting of: lambda exonuclease, signal probes and hybridization buffer ingredients (Buffer-1 and Buffer-2).
{3}------------------------------------------------
Comparison to technological features of the predicate devices:
.
The following is a comparison of the GenMark Diagnostics eSensor® Warfarin Sensitivity Saliva Test on the XT-8 System to the predicate: Warfarin Sensitivity Test (K073720)
| Characteristic | eSensor® Warfarin Sensitivity Test(Predicate: K073720) | eSensor® Warfarin Sensitivity Saliva Test |
|---|---|---|
| Test type | Qualitative genetic test for single nucleotidepolymorphism detection | Same as predicate |
| Sample Type | Genomic DNA obtained from a human whole bloodsample | Genomic DNAobtained from ahuman saliva sample |
| Target ofdetection | Single-nucleotide polymorphism | Same as predicate |
| DNA extraction | Performed off-line | Same as predicate |
| Genes | CYP450 2C9 gene *2 alleleCYP450 2C9 gene *3 alleleVKORC1 gene -1639G>A polymorphism | Same as predicate |
| Number of Locigenotyped | 3 | Same as predicate |
| Genotypingreaction location | Test cartridge | Same as predicate |
| Genotypingprinciple | Sandwich hybridization test | Same as predicate |
| Instrumentoperating system | eSensor® Instrument Model XT-8 Random accesscompatible with multiple simultaneous test types. | Same as predicate |
| Assay results | Assay signal results are interpreted by a softwareprogram and are assigned a result that is presentedto the end-user in a report format | Same as predicate |
{4}------------------------------------------------
Performance Characteristics:
Method Comparison
In a method comparison study, a total of 316 gDNA samples extracted from saliva specimen with A260-280 ratios of 1.2-2.1 were genotyped using the eSensor® Warfarin Sensitivity Saliva Test and DNA sequencing.
r
| Before Retest | |||
|---|---|---|---|
| DNA SequencingResult | 2C9 wt/wt | 2C9 wt/*2 | 2C9*2/*2 |
| Correct Calls | 234 | 69 | 9 |
| No-Calls | 3 | 0 | 0 |
| Miscalls¹ | 0 | 1 | 0 |
| %Agreement | 98.7% | 98.6% | 100.0% |
| 95% LCB | 96.8% | 93.4% | 71.7% |
| DNA SequencingResult | 2C9 wt/wt | 2C9 wt/*3 | 2C9 *3/*3 |
| Correct Calls | 274 | 34 | 3 |
| No-Calls | 3 | 0 | 0 |
| Miscalls² | 2 | 0 | 0 |
| %Agreement | 98.2% | 100.0% | 100.0% |
| 95% LCB | 96.3% | 91.6% | 36.8% |
| DNA SequencingResult | VKORC1 | VKORC1 | VKORC1 |
| Correct Calls | G/G | G/A | A/A |
| Correct Calls | 120 | 131 | 62 |
| No-Calls | 2 | 1 | 0 |
| Miscalls | 0 | 0 | 0 |
| %Agreement | 98.4% | 99.2% | 100.0% |
| 95% LCB | 94.9% | 96.5% | 95.3% |
,
{5}------------------------------------------------
| eSensor® Warfarin Sensitivity Saliva Test Method ComparisonAfter Retest | |||
|---|---|---|---|
| DNA SequencingResult | 2C9 wt/wt | 2C9 wt/*2 | 2C9*2/*2 |
| Correct Calls | 237 | 69 | 9 |
| No-Calls | 0 | 0 | 0 |
| Miscalls1 | 0 | 1 | 0 |
| %Agreement | 100.0% | 98.6% | 100.0% |
| 95% LCB | 98.7% | 93.4% | 71.7% |
| DNA SequencingResult | 2C9 wt/wt | 2C9 wt/*3 | 2C9 *3/*3 |
| Correct Calls | 277 | 34 | 3 |
| No-Calls | 0 | 0 | 0 |
| Miscalls2 | 2 | 0 | 0 |
| %Agreement | 99.3% | 100.0% | 100.0% |
| 95% LCB | 97.8% | 91.6% | 36.8% |
| DNA SequencingResult | VKORC1 | VKORC1 | VKORC1 |
| Result | G/G | G/A | A/A |
| Correct Calls | 122 | 132 | 62 |
| No-Calls | 0 | 0 | 0 |
| Miscalls | 0 | 0 | 0 |
| %Agreement | 100.0% | 100.0% | 100.0% |
| 95% LCB | 97.6% | 97.8% | 95.3% |
Interference Substances
Effect of Endogenous Interfering Substances: Interfering substances including salivary a-amylase, hemoglobin, immunoglobulin A (IgA) and total protein were spiked into saliva samples at the highest amounts found in literature. 10 donors provided five saliva samples each spiked with one of the four interfering substances. A control sample was included. Three extractions were performed on each sample. There was 100% agreement between the eSensor® Warfarin Sensitivity Saliva Test results and bidirectional DNA sequencing for all test substances in first pass, demonstrating no effect of any interfering substances on genotyping.
{6}------------------------------------------------
| Substance | Concentration | Samples Tested | Correct Calls | Incorrect Calls | No-Calls | % Agreement |
|---|---|---|---|---|---|---|
| Control | NA | 30 | 30 | 0 | 0 | 100% |
| Amylase | 260 ± 45 U/mL | 30 | 30 | 0 | 0 | 100% |
| Hemoglobin | 20 mg/mL | 30 | 30 | 0 | 0 | 100% |
| IgA | 188 ± 80 mg/L | 30 | 30 | 0 | 0 | 100% |
| Total Protein | 1.46 ± 0.4 mg/mL | 30 | 30 | 0 | 0 | 100% |
Effect of Exogenous Interfering Substances: Potentially interfering exogenous substances (eating, drinking, chewing gum, using mouthwash and smoking) introduced into saliva samples through various activities were tested. Each activity group was composed of five donors who each provided samples for baseline, immediate and 30 minutes. Three samples per donor were tested. There was 100% agreement between the eSensor® Warfarin Sensitivity Saliva Test results and bidirectional DNA sequencing for all activities tested in first pass, demonstrating no effect of any interfering substances on genotyping.
| Activity | Time-point | SamplesTested | Correct Calls | IncorrectCalls | No-Calls | %Agreement |
|---|---|---|---|---|---|---|
| Eating | Baseline | 15 | 15 | 0 | 0 | 100% |
| Eating | Immediate | 15 | 15 | 0 | 0 | 100% |
| Eating | 30 minutes | 15 | 15 | 0 | 0 | 100% |
| Drinking | Baseline | 15 | 15 | 0 | 0 | 100% |
| Drinking | Immediate | 15 | 15 | 0 | 0 | 100% |
| Drinking | 30 minutes | 15 | 15 | 0 | 0 | 100% |
| Chewing Gum | Baseline | 15 | 15 | 0 | 0 | 100% |
| Chewing Gum | Immediate | 15 | 15 | 0 | 0 | 100% |
| Chewing Gum | 30 minutes | 15 | 15 | 0 | 0 | 100% |
| Mouthwash | Baseline | 15 | 15 | 0 | 0 | 100% |
| Mouthwash | Immediate | 15 | 15 | 0 | 0 | 100% |
| Mouthwash | 30 minutes | 15 | 15 | 0 | 0 | 100% |
| Smoking | Baseline | 15 | 15 | 0 | 0 | 100% |
| Smoking | Immediate | 15 | 15 | 0 | 0 | 100% |
| Smoking | 30 minutes | 15 | 15 | 0 | 0 | 100% |
Conclusion:
The above clinical test results support the safety and effectiveness of the eSensor® Warfarin Sensitivity Saliva Test on the eSensor® XT-8 System, and demonstrate substantial equivalence to the predicate device.
eSensor® is a registered trademark of CMS dba GenMark and its subsidiaries
{7}------------------------------------------------
Image /page/7/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the seal is an abstract symbol resembling a stylized human figure or bird.
10903 New Hampshire Avenue Silver Spring, MD 20993
GenMark Diagnostics, Inc. c/o John Riolo 5964 La Place Court, Suite 100 Carlsbad, CA 92008
DEC - 2 2011
Re: K110786 Trade Name: eSensor Warfarin Sensitivity Saliva Test Regulation Number: 21 CFR §862.3360 Regulation Name: Drug Metabolizing Enzyme Genotyping System Regulatory Class: Class II Product Codes: ODW, ODV, NSU Dated: October 24, 2011 Received: October 27, 2011
Dear Mr. Riolo:
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); 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 (QS) regulation (21 CFR Part 820).
{8}------------------------------------------------
Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), 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 postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical
Devices/Safety/ReportaProblem/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) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm
Sincerely yours.
N
Counney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{9}------------------------------------------------
Indications for Use Form
510(k) Number (if known): K110786
Device Name: eSensor® Warfarin Sensitivity Saliva Test
Indications for Use:
The eSensor® Warfarin Sensitivity Saliva 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 qenomic DNA extracted from human saliva samples collected using the the Oragene® Dx Device, as an aid in the identification of patients at risk for increased warfarin sensitivity.
Prescription 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)
Signature
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k): K110786
Page 1 of 1
§ 862.2570 Instrumentation for clinical multiplex test systems.
(a)
Identification. Instrumentation for clinical multiplex test systems is a device intended to measure and sort multiple signals generated by an assay from a clinical sample. This instrumentation is used with a specific assay to measure multiple similar analytes that establish a single indicator to aid in diagnosis. Such instrumentation may be compatible with more than one specific assay. The device includes a signal reader unit, and may also integrate reagent handling, hybridization, washing, dedicated instrument control, and other hardware components, as well as raw data storage mechanisms, data acquisition software, and software to process detected signals.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Instrumentation for Clinical Multiplex Test Systems.” See § 862.1(d) for the availability of this guidance document.