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.

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text.

It's important to note that this document is a 510(k) summary, which often focuses on demonstrating substantial equivalence to an existing device rather than presenting a full, de novo validation study. Therefore, some of the requested information, particularly regarding initial clinical validation or ground truth establishment for the original device, might not be explicitly detailed. The acceptance criteria described here pertain to demonstrating performance after modifications to an already cleared device.

Acceptance Criteria and Device Performance for Modified Tissue of Origin Test Kit-FFPE

The acceptance criteria here refer to the demonstration that two specific modifications (reagent change and software update) to an already cleared device (Pathwork Tissue of Origin Test Kit FFPE, K120489) did not negatively impact its performance. The primary metric used is concordance with the previous, validated method.

1. Table of Acceptance Criteria and Reported Device Performance

Feature/Modification	Acceptance Criteria (Implicit from Study Design)	Reported Device Performance
Reagent Comparison	High concordance (e.g., >80% or similar to original performance) with the original RampUp RNA Amplification Kit. All pre-established criteria were met or exceeded.	90.8% concordance (95% CI: 83.6%, 95.3%) with original RampUp RNA Amplification Kit.
Software Comparison	High concordance (e.g., >95% or 100%) with the original Genechip™ System 3000 Dx software.	100% concordance (95% CI: 95.9%, 100%) with original Dx software.

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

Test Set Sample Size:
- Reagent Comparison: 142 specimens
- Software Comparison: 20 specimens
Data Provenance: The specimens were "randomly selected from FFPE tumor specimens employed for assessment of performance during development of the original TOO-FFPE kit." This indicates the data is retrospective, using archived samples. The country of origin is not specified, but the context of an FDA submission implies commercial use in the US, suggesting data likely from US/North American sources, though not explicitly stated.

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

This information is not provided in the document. The studies assess concordance between the modified and original methods, implying the "truth" is established by the original method's result for the sample. The original device's clearance (K092967, K120489) would have involved establishing its ground truth based on clinical and pathological practice, but the details are not replicated here for this 510(k) summary focused on modifications.

4. Adjudication Method for the Test Set

This information is not applicable in the context of these specific studies. The studies are comparing the output of a modified process against the output of the original, previously cleared process for the same samples. Discrepancies are noted as "discordance" rather than requiring expert adjudication of a "ground truth" difference, as the reference is the prior method's output.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No, an MRMC comparative effectiveness study was not conducted. This device is an in vitro diagnostic (IVD) test measuring molecular expression patterns, not an imaging AI designed to assist human readers. The outputs are numerical similarities to pre-defined tumor types, not interpretations for human review.

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

Yes, the performance described is standalone (algorithm only). The device, the "Tissue of Origin Test Kit-FFPE," measures RNA expression patterns and provides a similarity score. The studies assess the consistency of these scores between modified and original methods, which is a direct output of the algorithm and associated lab processes without human interpretation as part of the core performance evaluation.

7. The Type of Ground Truth Used

For the purpose of these modification studies, the "ground truth" for each sample's classification is implicitly the result obtained from the original, previously cleared and validated method. The studies aim to show that the new modifications yield the same result as the established method. The ultimate ground truth for the original validation of the TOO-FFPE test, as stated in its Indications for Use, was based on "diagnosed according to then current clinical and pathological practice" for the 15 tumor types in its database. This would typically involve expert consensus diagnostics (e.g., pathology reports, clinical history).

8. The Sample Size for the Training Set

The sample size for the training set is not specified in this document. This 510(k) summary pertains to modifications of an already developed and trained device. The original development and validation of the "Tissue of Origin Test Kit-FFPE" (K092967 / K120489) would have involved a training set, but its details are not part of this summary for a modified device. The document mentions the "database of fifteen tumor types" against which patient samples are compared, which serves as the trained model/reference.

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

How the ground truth for the original training set was established is not detailed in this document.
- However, the Indications for Use states that the database samples were "diagnosed according to then current clinical and pathological practice." This typically means that the ground truth for the 15 tumor types in the database was established by expert consensus diagnoses based on a combination of clinical history, pathological findings (histology, immunohistochemistry), and potentially other diagnostic tests. This implies a rigorous, multi-modal diagnostic approach by qualified medical professionals (e.g., pathologists, oncologists).

Summary

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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.

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 StreetLos 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 geneexpression-based diagnostics
Classification:	21 CFR § 862.3100, Amphetamine Test SystemClass II
Product Code:	OIW, Software, similarity score algorithm, tissue of origin formalignant 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

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.

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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-FFPEK092967	Tissue of Origin Test Kit-FFPEK120489	Modified Tissue of Origin TestKit- FFPE
		Substantially equivalent to K092967cleared on May 17, 2012
Intended use	The Pathwork Tissue of Origin Test isan in vitro diagnostic intended tomeasure the degree of similaritybetween the RNA expression patterns ina patient's formalin fixed, paraffinembedded (FFPE) tumor and the RNAexpression patterns in a database offifteen tumor types (poorlydifferentiated, undifferentiated, andmetastatic cases) that were diagnosedaccording to then current clinical andpathological practice. This test shouldbe evaluated by a qualified physician inthe context of the patient's clinicalhistory and other diagnostic test results.	Same	Same
Microarray	Pathchip®	Same chip, same location of all geneexpression probes.	Same chip, same location of allgene expression probes.
Equipment
	Hybridization oven	Same	Same
	Stain, wash	Same	Same
	Scanner	Same	Same
	Software	Same	Changed to Genechip™ System3000 Dx v.2
Extraction	As described in K092967	Same	Same
Amplification	As described in K092967	Changed to: Allow a minimum of30ng total RNA extracted fromtissue specimen is required at aconcentration of 10 ng/uI (± 0.5ng/uI).	Changed to GeneChip™ 3' IVTPico Kit
Purification ofbiotinylated cDNA	As Described in the Labeling inK092967	Changed, Added EtOH	Changed to GeneChip™ 3' IVTPico Kit
Internal ProcessingQuality Control(Data Verification)	Percent PositiveOverall SignalRegional Discontinuity	Same	Same
Software	FTP	Same	Same
Analysis	Algorithm as described in K092967	Same	Same
Report	Graphic presentation of SimilarityScores 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.1. Reagent Comparison:N=142, randomly selected from the 15 subtypesAgreement, 90.8% (83.6, 95.3)2. Software Comparison:N=20, randomly selectedAgreement, 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 theRampUp RNA Amplification Kit and the GeneChip™ 3' IVT Pico Kit
Comparison	#Specimens	Concordance			Discordance
		Ratio	Percent	95%ConfidenceInterval	Ratio	Percent	95%ConfidenceInterval
RampUpVersusPico	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 DxSoftware and Dx v.2 Software
		Concordance			Discordance
Comparison	#Specimens	Ratio	Percent	95%ConfidenceInterval	Ratio	Percent	95%ConfidenceInterval
DxVersusDx 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)

Regulation Number and Section

§ 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).