The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro disgnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.

The Virtuoso™ System for IHC ER (SPI) is for digital read and image analysis spplications. This particular Virtures system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded neoplastic tissue. This device is sn accessory to Ventana Medical Systems, Inc. CONFIRM™ anti-Estrogan Receptor (ER) (SPI) Rabbit Monoclonal Primary Antibody assay. The CONFIRM™ anti- ER (SPI) Rabbit Monoclonal Primary Antibody assay is indicated for use as an aid in the assessment of breast cancer patients for whom endocrine treatment is being considered (but is not the sole basis for treatment).

Note: The IHC ER (SPI) Digital Read and Image Analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and measurement of images from microscope glass slides of breast cancer specified for the presence of ER protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on the immunobistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the CONFIRM™ ani-Estrogen Receptor (RR) (SPI) Rabit Monoclonal Primary Antibody used to assure the validity of the Virtusso System for IBC ER Digital Read and Invage Analysis scores. The actual correlation of CONFIRM anti-Estrogen Receptor (ER)(SPI) Rabbit Monocload Antibody to clinical outcome has not been established.

Device Description

Not Found

AI/ML Overview

This detailed response is based on the provided text, but it's important to note that the document is a 510(k) clearance letter and not the 510(k) summary itself. Therefore, specific details about the study design, sample sizes for training, and ground truth establishment in the scientific study are not explicitly present in this document. The information provided heavily relies on the content within the "Indications for Use" section.

Here's the breakdown based on the input document:

Acceptance Criteria and Device Performance Study for Virtuoso System for IHC ER(SP1)

The Virtuoso System for IHC ER (SP1) is intended as an aid to the pathologist for digital read and image analysis applications in the detection and semi-quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded neoplastic tissue, specifically in breast cancer.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state quantitative acceptance criteria (e.g., minimum sensitivity, specificity, or agreement rates) or detailed reported device performance metrics from a specific study. Instead, the "Indications for Use" section describes the intended functionality and adjunctive nature of the device.

The qualitative "acceptance criteria" can be inferred from the device's stated purpose: "an aid to the pathologist in the detection and semi-quantitative measurement of estrogen receptor (ER) protein in formalin-fixed, paraffin-embedded neoplastic tissue." The "reported device performance" is that the system fulfills this role as an adjunctive, computer-assisted methodology, requiring pathologist verification.

Acceptance Criteria Category	Specific Criteria (Inferred from "Indications for Use")	Reported Device Performance (Inferred/Stated)
Functionality	Aid in detection of ER protein	Provides computer-assisted detection of ER protein
Quantification	Aid in semi-quantitative measurement of ER protein	Provides computer-assisted semi-quantitative measurement of ER protein
User Role	Adjunctive tool for qualified pathologist	Designed to be used by qualified pathologists as an aid; pathologist verification required
Tissue Type	Formalin-fixed, paraffin-embedded neoplastic tissue	Designed for this specific tissue type (breast cancer)
Clinical Context	Assessment of breast cancer patients for endocrine treatment consideration	Intended for this clinical application (not sole basis for treatment)
Immunohistochemistry	Accuracy dependent on IHC staining quality	Acknowledges dependency on upstream IHC staining validity
Correlation	Not the sole basis for treatment	Reaffirms that the device is an aid, not a definitive basis for treatment decisions
Validation	Pathologist verification of Image Analysis software score agreement	Pathologist is responsible for verifying agreement with software scores

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

The provided 510(k) clearance letter and "Indications for Use" statement do not contain information regarding the specific sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective nature). These details would typically be found in the 510(k) summary document or the underlying study report.

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

The provided document does not specify the number of experts used to establish the ground truth for the test set or their qualifications. However, it does emphasize that the device is an "aid to the pathologist" and that "It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified...to assure the validity of the Virtusso System for IBC ER Digital Read and Invage Analysis scores." This implies that qualified pathologists are central to the interpretation and validation process.

4. Adjudication Method for the Test Set

The document does not specify the adjudication method used for the test set.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size.

The provided document does not indicate whether a MRMC comparative effectiveness study was done, nor does it provide any effect size of how much human readers improve with AI vs. without AI assistance. The language ("adjunctive computer-assisted methodologies") suggests the device is intended to assist, but no performance metrics for this assistance are given in this document.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Study was done.

The provided document does not explicitly state if a standalone performance study was conducted. However, the consistent phrasing "aid to the pathologist" and "pathologist should verify agreement with the Image Analysis software application score" strongly implies that the device is not intended for standalone interpretation and its performance is always considered in conjunction with a human expert.

7. The Type of Ground Truth Used

The document implies that the ground truth for evaluation would be established by expert consensus/pathologist assessment, particularly given the statement: "The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls..." This suggests that expert pathological review, potentially supported by appropriate controls and validated IHC staining, forms the basis of ground truth. There is no mention of pathology reports as the sole ground truth, or outcomes data.

8. The Sample Size for the Training Set

The provided document does not contain information regarding the sample size used for the training set.

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

The provided document does not contain information on how the ground truth for the training set was established. Given the nature of the device, it is highly probable that expert pathologists would have been involved in establishing the ground truth for training data, similar to the inference for the test set ground truth.

Summary

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

November 22, 2013

VENTANA MEDICAL SYSTEMS, INC. ERIKA AMMIRATI 575 SHIRLYNN COURT LOS ALTOS CA 94022

Re: K130515

Trade/Device Name: Virtuoso System For IHC ER(SP1) Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: II Product Code: NQN, OEO, NOT Dated: February 26, 2013 Received: March 1, 2013

Dear Ms. Ammirati:

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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) 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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Page 2-Ms. Ammirati

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours.

Reena Philip -S

for

Maria M. Chan Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

510{k) Number (if known) K130512

Device Name

Virtuosoma System for IHC ER (SP1)

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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Regulation Number and Section

§ 864.1860 Immunohistochemistry reagents and kits.

(a)
Identification. Immunohistochemistry test systems (IHC's) are in vitro diagnostic devices consisting of polyclonal or monoclonal antibodies labeled with directions for use and performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for use with flow cytometry devices are not considered IHC's.(b)
Classification of immunohistochemistry devices. (1) Class I (general controls). Except as described in paragraphs (b)(2) and (b)(3) of this section, these devices are exempt from the premarket notification requirements in part 807, subpart E of this chapter. This exemption applies to IHC's that provide the pathologist with adjunctive diagnostic information that may be incorporated into the pathologist's report, but that is not ordinarily reported to the clinician as an independent finding. These IHC's are used after the primary diagnosis of tumor (neoplasm) has been made by conventional histopathology using nonimmunologic histochemical stains, such as hematoxylin and eosin. Examples of class I IHC's are differentiation markers that are used as adjunctive tests to subclassify tumors, such as keratin.(2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer.
(3) Class III (premarket approval). IHC's intended for any use not described in paragraphs (b)(1) or (b)(2) of this section.
(c)
Date of PMA or notice of completion of a PDP is required. As of May 28, 1976, an approval under section 515 of the Federal Food, Drug, and Cosmetic Act is required for any device described in paragraph (b)(3) of this section before this device may be commercially distributed. See § 864.3.