(87 days)
Unknown
The description mentions "software" for comparing RNA expression patterns to a database, which could potentially utilize ML algorithms for pattern matching and classification. However, the document does not explicitly state the use of AI or ML, nor does it provide details about the software's internal workings or training data, which would be expected if AI/ML were a core component.
No
The device is an in vitro diagnostic (IVD) test that measures RNA expression patterns to aid in the diagnosis of tumor origin, it does not provide any treatment or therapeutic effect.
Yes.
Explanation: The "Intended Use / Indications for Use" section explicitly states "The Cancer Genetics Tissue of Origin Test is an in vitro diagnostic intended to measure the degree of similarity...". This explicitly states its purpose is diagnostic.
No
The device description explicitly states that the product consists of a reagent kit, instructions, a microchip, and software. It also requires external hardware like an Affymetrix GeneChip Fluidics Station and Scanner. Therefore, it is not a software-only medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the test is an "in vitro diagnostic."
- Device Description: The "Device Description" section describes the product as an "in vitro diagnostic product consisting of a reagent kit and instructions, plus a microchip and software."
- Nature of the Test: The test analyzes RNA expression patterns in a patient's tumor sample (taken in vitro, outside the body) to aid in diagnosis.
These points clearly align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Cancer Genetics Tissue of Origin Test is an in vitro diagnostic intended to measure the degree of similarity between the RNA expression patterns in a patient's formalin-fixed, paraffin-embedded (FFPE) tumor and the RNA expression patterns in a database of fifteen tumor types (poorly differentiated, undifferentiated and metastatic cases) that were diagnosed according to then current clinical and pathological practice. This test should be evaluated by a qualified physician in the context of the patient's clinical history and other diagnostic test results.
Limitations: The Cancer Genetics Tissue of Origin Test is not intended to establish the origin of tumors (e.g., cancer of unknown primary) that cannot be diagnosed according to current clinical and pathological practice. It is not intended to subclassify or modify the classification of tumors that can be diagnosed by current clinical and pathological practice, nor to predict disease course or survival or treatment efficacy, nor to distinguish primary from metastatic tumor. Tumor types not in the Cancer Genetics Tissue of Origin Test database may have RNA expression patterns that are similar to patterns in the database. Therefore, results cannot be used to distinguish tumor types in the database from tumor types not in the database.
Product codes
OIW
Device Description
The modified and the predicate devices (K092967 and K120489) are all in vitro diagnostic product consisting of a reagent kit and instructions, plus a microchip and software, for the comparison of the RNA expression pattern of a patient's tumor sample to a database of 15 known tumor tissues. Equipment required but not provided are an Affymetrix GeneChip Fluidics Station FS450Dx v2 and an Affymetrix GeneChip Scanner GCS3000Dx, attached to an Affymetrix Workstation with GeneChip Operating System (GCOS). Additional equipment required but not provided is commonly available laboratory equipment.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Tumor
Indicated Patient Age Range
Not Found
Intended User / Care Setting
qualified physician
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
A set of randomly selected tumor specimens analyzed previously using the 510(k) cleared method, were also analyzed using the modified method, and the results were compared.
The modified method used GeneChip™ 3' IVT Pico Kit to perform target preparation while in the original 510(k) cleared method used the RampUp RNA amplification Kit. For this study, 142 specimens were selected from FFPE tumor specimens employed for assessment of performance during development of the original TOO-FFPE kit. The sample set included each of the tumor types in the database. Comparisons could be made for all 142 tumors.
The second modification to be assessed was the microarray processing software, which was upgraded from the Genechip™ System 3000 Dx (no longer supported by the manufacturer Affymetrix) to Genechip™ System 3000 Dx v.2 ( FDAcleared and CE marked for in vitro diagnostics use). For this study, 20 specimens were selected from reserves of FFPE tumor specimens employed for assessment of performance during development of the original TOO-FFPE kit and had also been analyzed using the GeneChip™ 3' IVT Pico Kit.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Two modifications were assessed (i) a change in the method and reagents for amplification and (ii) an update to the microarray processing software.
A set of randomly selected tumor specimens analyzed previously using the 510(k) cleared method, were also analyzed using the modified method, and the results were compared.
The modified method used GeneChip™ 3' IVT Pico Kit to perform target preparation while in the original 510(k) cleared method used the RampUp RNA amplification Kit. For this study, 142 specimens were selected from FFPE tumor specimens employed for assessment of performance during development of the original TOO-FFPE kit. The sample set included each of the tumor types in the database. Comparisons could be made for all 142 tumors. 133 of these were concordant and 9 were not, for a % concordance of 90.8% (95% confidence interval of 83.6%, 95.3%). The change was considered validated, because all pre-established criteria were met or exceeded.
The second modification to be assessed was the microarray processing software, which was upgraded from the Genechip™ System 3000 Dx (no longer supported by the manufacturer Affymetrix) to Genechip™ System 3000 Dx v.2 ( FDAcleared and CE marked for in vitro diagnostics use). For this study, 20 specimens were selected from reserves of FFPE tumor specimens employed for assessment of performance during development of the original TOO-FFPE kit and had also been analyzed using the GeneChip™ 3' IVT Pico Kit. For all 20 samples, the results were concordant between Dx and Dx v.2.
Conclusion: The minor software and reagent changes have not changed the performance of the Test.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Concordance for reagent comparison: 90.8% (95% confidence interval of 83.6%, 95.3%)
Concordance for software comparison: 100% (95% confidence interval of 95.9%, 100%)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 862.3100 Amphetamine test system.
(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. 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, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).
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March 15, 2018
Cancer Genetics, Inc. Victoria Kusel Senior Corporate Legal Associate 133 Southcenter Court Morrisville, NC 27560
Re: K173839
Trade/Device Name: Tissue of Origin Test Kit-FFPE Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: OIW Dated: December 15, 2017 Received: December 18, 2017
Dear Ms. Victoria Kusel:
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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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/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Yun-fu Hu -S
for Reena Philip, Ph.D. Director Division of Molecular Genetics and Pathology Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K173839
Device Name Tissue of Origin Test Kit-FFPE
Indications for Use (Describe)
Indication for Use: The Cancer Genetics Tissue of Origin Test is an in vitro diagnostic intended to measure the degree of similarity between the RNA expression patterns in a patient's formalin-fixed, paraffin-embedded (FFPE) tumor and the RNA expression patterns in a database of fifteen tumor types (poorly differentiated, undifferentiated and metastatic cases) that were diagnosed acording to then current clinical and pathological practice. This test should be evaluated by a qualified physician in the context of the patient's clinical history and other diagnostic test results.
Limitations: The Cancer Genetics Tissue of Origin Test is not intended to establish the origin of tumors (e.g., cancer of unknown primary) that cannot be diagnosed according to current clinical and pathological practice. It is not intended to subclassify or modify the classification of tumors that can be diagnosed by current clinical and pathological practice, nor to predict disease course or survival or treatment efficacy, nor to distinguish primary from metastatic tumor. Tumor types not in the Cancer Genetics Tissue of Origin Test database may have RNA expression patterns that are similar to patterns in the database. Therefore, results cannot be used to distinguish tumor types in the database from tumor types not in the database.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned Special 510(k) number is K173839.
Date Prepared: December 15, 2017
| 807.92 (a)(1): | Name: | Cancer Genetics, Inc. |
|---|---|---|
| Address: | 1640 Marengo Street | |
| Los Angeles, CA 90033 | ||
| Phone: | (213) 863-0175 | |
| Contact: | Janet A. Graff, Quality Assurance Manager | |
| Fax: | (323) 224-3096 |
807.92 (a)(2): Device Name – trade name and common name, and classification
| Trade name: | Cancer Genetics Tissue of Origin Test Kit-FFPE |
|---|---|
| Common name: | Microarray, reagents and software system kit for gene |
| expression-based diagnostics | |
| Classification: | 21 CFR § 862.3100, Amphetamine Test System |
| Class II | |
| Product Code: | OIW, Software, similarity score algorithm, tissue of origin for |
| malignant tumor types | |
| Panel: | Toxicology (91) |
807.92 (a)(3): Identification of the legally marketed predicate device
The Cancer Genetics Tissue of Origin Test Kit-FFPE as modified is substantially equivalent to the Pathwork Tissue of Origin Test Kit FFPE cleared under premarket notification K120489 on May 17, 2012 (which is substantially equivalent to the Pathwork Tissue of Origin Test Kit FFPE cleared under premarket notification K092967).
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807.92 (a)(4): Device Description
The modified and the predicate devices (K092967 and K120489) are all in vitro diagnostic product consisting of a reagent kit and instructions, plus a microchip and software, for the comparison of the RNA expression pattern of a patient's tumor sample to a database of expression patterns of 15 known tumor tissues. Equipment required but not provided are an Affymetrix GeneChip Fluidics Station FS450Dx v2 and an Affymetrix GeneChip Scanner GCS3000Dx, attached to an Affymetrix Workstation with GeneChip Operating System (GCOS). Additional equipment required but not provided is commonly available laboratory equipment.
807.92 (a)(5): Intended Use
The Cancer Genetics Tissue of Origin Test is an in vitro diagnostic intended to measure the degree of similarity between the RNA expression patterns in a patient's formalin-fixed, paraffin-embedded (FFPE) tumor and the RNA expression patterns in a database of fifteen tumor types (poorly differentiated, undifferentiated and metastatic cases) that were diagnosed according to then current clinical and pathological practice. This test should be evaluated by a qualified physician in the context of the patient's clinical history and other diagnostic test results.
Limitations: The Cancer Genetics Tissue of Origin Test is not intended to establish the origin of tumors (e.g., cancer of unknown primary) that cannot be diagnosed according to current clinical and pathological practice. It is not intended to subclassify or modify the classification of tumors that can be diagnosed by current clinical and pathological practice, nor to predict disease course or survival or treatment efficacy, nor to distinguish primary from metastatic tumor. Tumor types not in the Cancer Genetics Tissue of Origin Test database may have RNA expression patterns that are similar to patterns in the database. Therefore, results cannot be used to distinguish tumor types in the database from tumor types not in the database.
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| 807.92 (a)(6): Technological Similarities and Differences to Predicate | ||
|---|---|---|
| Comparison with Unmodified Device | |||
|---|---|---|---|
| Feature/ component | Tissue of Origin Test Kit-FFPE | ||
| K092967 | Tissue of Origin Test Kit-FFPE | ||
| K120489 | Modified Tissue of Origin Test | ||
| Kit- FFPE | |||
| Substantially equivalent to K092967 | |||
| cleared on May 17, 2012 | |||
| Intended use | The Pathwork Tissue of Origin Test is | ||
| an in vitro diagnostic intended to | |||
| measure the degree of similarity | |||
| between the RNA expression patterns in | |||
| a patient's formalin fixed, paraffin | |||
| embedded (FFPE) tumor and the RNA | |||
| expression patterns in a database of | |||
| fifteen tumor types (poorly | |||
| differentiated, undifferentiated, and | |||
| metastatic cases) that were diagnosed | |||
| according to then current clinical and | |||
| pathological practice. This test should | |||
| be evaluated by a qualified physician in | |||
| the context of the patient's clinical | |||
| history and other diagnostic test results. | Same | Same | |
| Microarray | Pathchip® | Same chip, same location of all gene | |
| expression probes. | Same chip, same location of all | ||
| gene expression probes. | |||
| Equipment | |||
| Hybridization oven | Same | Same | |
| Stain, wash | Same | Same | |
| Scanner | Same | Same | |
| Software | Same | Changed to Genechip™ System | |
| 3000 Dx v.2 | |||
| Extraction | As described in K092967 | Same | Same |
| Amplification | As described in K092967 | Changed to: Allow a minimum of | |
| 30ng total RNA extracted from | |||
| tissue specimen is required at a | |||
| concentration of 10 ng/uI (± 0.5 | |||
| ng/uI). | Changed to GeneChip™ 3' IVT | ||
| Pico Kit | |||
| Purification of | |||
| biotinylated cDNA | As Described in the Labeling in | ||
| K092967 | Changed, Added EtOH | Changed to GeneChip™ 3' IVT | |
| Pico Kit | |||
| Internal Processing | |||
| Quality Control | |||
| (Data Verification) | Percent Positive | ||
| Overall Signal | |||
| Regional Discontinuity | Same | Same | |
| Software | FTP | Same | Same |
| Analysis | Algorithm as described in K092967 | Same | Same |
| Report | Graphic presentation of Similarity | ||
| Scores for fifteen tissues of origin | Same | Same | |
| Comparison with Unmodified Device | |||
| Feature/ component | Tissue of Origin Test Kit-FFPE K092967 | Tissue of Origin Test Kit-FFPE K120489 | Modified Tissue of Origin Test Kit- FFPE |
| Extraction Reagents | As K092967 | Same | Same |
| Amplification Reagents | As K092967 | Same | Changed to GeneChip™ 3' IVT Pico Kit |
| Analyte Detected on Chip | cDNA | Same | Same |
| Probes employed in test | 2000 | Same | Same |
| % Agreement with available diagnosis ("accuracy") | N= 462 (≥ 25 for each of 15 malignant tumor types). Agreement, 88.5% (85.3,91.3) | Percent agreement with result reported by original method, vs. reported by changed method. N=45, 3 per tissue attempted. 43 actually analyzed, 1 quality failure, 1 unusable because original test result with unavailable for comparison. Agreement, 99.7% (87.7, 99.9) | Percent agreement with result reported by original method, vs. reported by changed method. |
- Reagent Comparison:
N=142, randomly selected from the 15 subtypes
Agreement, 90.8% (83.6, 95.3) - Software Comparison:
N=20, randomly selected
Agreement, 100% (95.9, 100) |
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807.92 (b)(1): Brief Description of Non-clinical data
Two modifications were assessed (i) a change in the method and reagents for amplification and (ii) an update to the microarray processing software.
A set of randomly selected tumor specimens analyzed previously using the 510(k) cleared method, were also analyzed using the modified method, and the results were compared.
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The modified method used GeneChip™ 3' IVT Pico Kit to perform target preparation while in the original 510(k) cleared method used the RampUp RNA amplification Kit. For this study, 142 specimens were selected from FFPE tumor specimens employed for assessment of performance during development of the original TOO-FFPE kit. The sample set included each of the tumor types in the database. Comparisons could be made for all 142 tumors. 133 of these were concordant and 9 were not, for a % concordance of 90.8% (95% confidence interval of 83.6%, 95.3%). The change was considered validated, because all pre-established criteria were met or exceeded.
| Concordance in Tissue of Origin Test Results Between Paired Specimens Processed with the
| RampUp RNA Amplification Kit and the GeneChip™ 3' IVT Pico Kit | |||||||
|---|---|---|---|---|---|---|---|
| Comparison | # | ||||||
| Specimens | Concordance | Discordance | |||||
| Ratio | Percent | 95% | |||||
| Confidence | |||||||
| Interval | Ratio | Percent | 95% | ||||
| Confidence | |||||||
| Interval | |||||||
| RampUp | |||||||
| Versus | |||||||
| Pico | 142 | 133/142 | 90.8% | [83.6, 95.3] | 9/142 | 9.2% | [5.7, 13.9] |
The second modification to be assessed was the microarray processing software, which was upgraded from the Genechip™ System 3000 Dx (no longer supported by the manufacturer Affymetrix) to Genechip™ System 3000 Dx v.2 ( FDAcleared and CE marked for in vitro diagnostics use). For this study, 20 specimens were selected from reserves of FFPE tumor specimens employed for assessment of performance during development of the original TOO-FFPE kit and had also been analyzed using the GeneChip™ 3' IVT Pico Kit. For all 20 samples, the results were concordant between Dx and Dx v.2.
| Concordance in Tissue of Origin Test Results Between Paired Specimens Processed with Dx
| Software and Dx v.2 Software | |||||||
|---|---|---|---|---|---|---|---|
| Concordance | Discordance | ||||||
| Comparison | # | ||||||
| Specimens | Ratio | Percent | 95% | ||||
| Confidence | |||||||
| Interval | Ratio | Percent | 95% | ||||
| Confidence | |||||||
| Interval | |||||||
| Dx | |||||||
| Versus | |||||||
| Dx v.2 | 20 | 20/20 | 100% | [95.9, 100] | 0/20 | 0% | N/A |
Conclusion: The minor software and reagent changes have not changed the performance of the Test.
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807.92 (b)(2): Brief Description of Clinical Data
No clinical data is provided in this special 510(k).
807.92 (b)(3): Conclusions from Clinical Testing
No clinical testing was provided in this special 510(k)