(276 days)
Not Found
No
The document describes "image analysis algorithms" and "computer-assisted methodologies" but does not mention AI, ML, or deep learning. The description emphasizes that the software makes "no independent interpretations of the data and requires competent human intervention for all steps in the analysis process," which is contrary to the typical characteristics of AI/ML systems.
No
The device is described as an image capture, management, analysis, and viewing system intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review, and classification of tissues and cells. It provides an aid to diagnosis, but does not directly treat a condition.
Yes
Explanation: The device is explicitly stated as being "intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest." It analyzes specific biomarkers (HER2, PR, ER, Ki67) in breast cancer tissue to assist in treatment considerations, which are all diagnostic functions.
No
The device description explicitly states that the device consists of hardware components including a slide capture camera, microscope, computer, monitor, keyboard, and mouse, in addition to the software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section explicitly states: "It is intended for in vitro diagnostic use as an aid to the pathologist..."
- Purpose: The device is designed to analyze biological specimens (formalin-fixed, paraffin-embedded breast cancer tissue) to provide information about specific markers (HER2, PR, ER, Ki67) that are used in the diagnosis and assessment of breast cancer.
- Clinical Context: The intended use is to aid a pathologist in making clinical decisions regarding patient treatment (e.g., considering HERCEPTIN® treatment, endocrine treatment).
- Accessory to IVD Reagents: The device is described as an accessory to specific primary antibodies (Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5), CONFIRMTM anti-Progesterone Receptor (PR) (1E2), CONFIRMTM anti-Estrogen Receptor (ER) (SP1), CONFIRMTM anti-Ki67 (30-9)), which are themselves IVD reagents used for immunohistochemical staining.
All these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The GenASIs HiPath IHC Family provides image capture, management, analysis, and viewing of specific immunohistochemically stained slides. It is intended for in vitro diagnostic 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 GenASIs HiPath IHC Family for HER2 (4B5) is for image capture and analysis applications. This particular system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2 protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
NOTE: The GenASIs HiPath IHC Family for HER2 (4BS) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and semi-quantitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of HER-2/neu receptor protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results on the quality of the immuchistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the GenASIs HiPath IHC Family for HER2 (4B5) image capture and analysis scores. The actual correlation of PATHWAY® anti-HER-2/neu (4B5) to clinical outcome has not been established.
- The GenASIs HiPath IHC Family for PR (1E2) is for image capture and analysis applications. This particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of progesterone receptor (PR) protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay. The CONFIRMTM anti-Progesterone Receptor (PR) (1E2) 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 GenASIs HiPath IHC for PR (1E2) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of PR protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody used to assure the validity of the GenASIs HiPath IHC Family for PR (1E2) image capture and analysis scores. The actual correlation of CONFIRMTM anti-PR antibody to clinical outcome has not been established.
- The GenASIs HiPath IHC Family for ER (SP1) is for image capture and analysis applications. The particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of ER (SP1): protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody. The Ventana Medical Systems, Inc. CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of ER status in breast cancer patients (but is not the sole basis for treatment).
Note: The GenASIs HiPath IHC Family for ER (SP1) image capture and analysis applications are adjunctive computerassisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer specimens stained for the protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the immuohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to assure the validity of the GenASIs HiPath IHC Family for ER (SP1) image capture and analysis scores. The actual correlation of CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to clinical outcome has not been established.
- The GenASIs HiPath IHC Family for Ki67 (30-9) is for image capture and analysis applications. The particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of Ki67 (30-9): protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRMTM anti-Ki67 (30-9) assay is indicated for use in assessing the activity of breast cancer tissue. When used with this assay, the GenASIs HiPath IHC Family for Ki67 (30-9) is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment). Note: The GenASIs HiPath IHC Family for Ki67 (30-9) image capture and analysis applications are adjunctive computerassisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer stained for the presence of Ki67 protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. 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 as specified in the instructions for the CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay to assure the validity of the GenASIs HiPath IHC Family for Ki67 (30-9) image capture and analysis scores. The actual correlation of CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary antibody assay to clinical outcome has not been established.
Product codes (comma separated list FDA assigned to the subject device)
NQN, NOT
Device Description
The GenASIs HiPath IHC Family, including software is designed to assist the qualified pathologist in the consistent assessment in inmmohistochemnically stained histologic sections from formalin-fixed, paraffin-embedded breast cancer tissues. The device consists of a slide capture camera, Microscope, computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Graphic User Interface (GUI).
The GenASIs HiPath IHC Family is an intranet-based, end-to-end, digital pathology software solution that allows pathology laboratories, to acquire, manage, view, analyze, share, and report test results of pathology specimens. Using the GenASIs HiPath IHC Family software the pathologist can view captured images, add annotations, make measurements, perform image analysis and generate reports.
Hardware: A camera based acquisition device designed to captures bright-field microscope digital images of formalin-fixed, paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide acquisition camera, X-Y Stage with holder adaptor for loading glass slides on a microscope and a workstation including a computer, keyboard, mouse and monitor.
Software: The GenASIs HiPath IHC Family software is designed to complement the routine workflow of a qualified pathologist in the review of immunohistochemically stained histologic slides. It allows the user to select fields of view (FOVs) in the digital image for analysis and provides quantitative data on these FOVs to assist with interpretation. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Bright-field microscope digital images
Anatomical Site
Breast cancer tissue/specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Qualified pathologist / Pathology laboratories
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
The clinical studies were based on comparison to the measures of agreement test of conventional manual evaluation through the microscope eyepieces, performed by pathologist that followed the recommendations of the Ventana user insertions for the different panel antibodies and test analysis performed with the proposed GenASIs HiPath IHC Family system, using the same stained slides.
The comparison study was conducted in three clinical sites, by three different pathologists, according to Applied Spectral Imaging's protocol. The study included a total of:
- HER2/neu (4B5) - 357 stained samples.
- PR (1E2) - 385 stained samples.
- ER (SP1) - 427 stained samples
- Ki67 (30-9) - 373 stained samples
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Study Type: Agreement study (comparison to manual evaluation) and Precision/Reproducibility (R&R) studies.
Sample Size:
- Agreement Study: HER2/neu (4B5) - 357 samples, PR (1E2) - 385 samples, ER (SP1) - 427 samples, Ki67 (30-9) - 373 samples.
- R&R Study: Forty (40) slides for each antibody (HER2/neu, ER, PR, Ki-67), totaling 160 slides.
Key Results:
Agreement Study (Manual vs GenASIs HiPath IHC Family pooled results):
- HER2/neu (4B5):
- Overall Agreement: 97%
- Positive Agreement: 98%
- Negative Agreement: 97%
- PR (1E2):
- Overall Agreement: 99%
- Positive Agreement: 98%
- Negative Agreement: 100%
- ER (SP1):
- Overall Agreement: 100%
- Positive Agreement: 99%
- Negative Agreement: 100%
- Ki67 (30-9):
- Overall Agreement: 96%
- Positive Agreement: 93%
- Negative Agreement: 97%
Precision/Reproducibility (R&R) Studies:
- HER2/neu (4B5): R&R agreements for positive and negative sample slides analysis showed high consistency across runs, days, and systems.
- Between-Run, Within-Day, Within-System: Average Positive Agreement ranged from 95.0% to 97.6%; Average Negative Agreement ranged from 95.0% to 97.5%.
- Between-Day, Within-System: Average Positive Agreement ranged from 97.6% to 100%; Average Negative Agreement ranged from 97.5% to 100%.
- Between-Systems: Average Positive Agreement ranged from 95.2% to 97.6%; Average Negative Agreement ranged from 95.2% to 97.6%.
- PR (1E2): Very high reproducibility.
- Between-Run, Within-Day, Within-System: 100% for both positive and negative agreement.
- Between-Day, Within-System: Average Positive Agreement ranged from 95.8% to 97.9%; Average Negative Agreement ranged from 93.8% to 97.1%.
- Between-Systems: Average Positive Agreement ranged from 97.9% to 100%; Average Negative Agreement ranged from 97.1% to 100%.
- ER (SP1): Excellent reproducibility.
- Between-Run, Within-Day, Within-System: 100% for both positive and negative agreement.
- Between-Day, Within-System: 100% for both positive and negative agreement.
- Between-Systems: 100% for both positive and negative agreement.
- Ki67 (30-9): High reproducibility, with slightly more variability in between-run results.
- Between-Run, Within-Day, Within-System: Average Positive Agreement ranged from 89.4% to 97.9%; Average Negative Agreement ranged from 84.9% to 97.1%.
- Between-Day, Within-System: 95.8% for positive and 93.8% for negative agreement across all day comparisons.
- Between-Systems: Average Positive Agreement ranged from 95.8% to 97.9%; Average Negative Agreement ranged from 93.8% to 97.1%.
AUC: Not Found
MRMC: Not Found
Standalone Performance: Not Found
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
See "Summary of Performance Studies" for "Overall Agreement", "Positive Agreement", and "Negative Agreement".
Predicate Device(s)
K111543, K111869, K130515, K111755
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 10, 2015
Applied Spectral Imaging Ltd. Ilan Sharon P.O. Box 4414 (A-109) Caesarea,30889 Isreal
Re: K140957
Trade/Device Name: GenASIs HiPath IHC Family Regulation Number: 21 CFR §864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: NON, NOT Dated: 12/11/2014 Received: 12/16/2014
Dear Ilan Sharon:
This letter corrects our substantially equivalent letter of January 15, 2015.
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
1
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.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education 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 Industry and Consumer Education 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
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
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Indications for Use
510(k) Number (if known) K140957
Device Name
GenASIs HiPath IHC Family
Indications for Use (Describe)
The GenASIs HiPath IHC Family provides image capture, management, analysis, and viewing of specific immunohistochemically stained slides. It is intended for in vitro diagnostic 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 GenASIs HiPath IHC Family for HER2 (4B5) is for image capture and analysis applications. This particular system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2 protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHWAY® anti-HER2/ neu (4B5) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
NOTE: The GenASIs HiPath IHC Family for HER2 (4BS) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and semi-quantitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of HER-2/neu receptor protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results on the quality of the immuchistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the GenASIs HiPath IHC Family for HER2 (4B5) image capture and analysis scores. The actual correlation of PATHWAY® anti-HER-2/neu (4B5) to clinical outcome has not been established.
- The GenASIs HiPath IHC Family for PR (1E2) is for image capture and analysis applications. This particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of progesterone receptor (PR) protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay. The CONFIRMTM anti-Progesterone Receptor (PR) (1E2) 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 GenASIs HiPath IHC for PR (1E2) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of PR protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody used to assure the validity of the GenASIs HiPath IHC Family for PR (1E2) image capture and analysis scores. The actual correlation of CONFIRMTM anti-PR antibody to clinical outcome has not been established.
- The GenASIs HiPath IHC Family for ER (SP1) is for image capture and analysis applications. The particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of ER (SP1): protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody. The Ventana Medical Systems, Inc. CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of ER status in breast cancer patients (but is not the sole basis for treatment).
Note: The GenASIs HiPath IHC Family for ER (SP1) image capture and analysis applications are adjunctive computerassisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from
3
microscope glass slides of breast cancer specimens stained for the protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the immuohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to assure the validity of the GenASIs HiPath IHC Family for ER (SP1) image capture and analysis scores. The actual correlation of CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to clinical outcome has not been established. 4. The GenASIs HiPath IHC Family for Ki67 (30-9) is for image capture and analysis applications. The particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of Ki67 (30-9): protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRMTM anti-Ki67 (30-9) assay is indicated for use in assessing the activity of breast cancer tissue. When used with this assay, the GenASIs HiPath IHC Family for Ki67 (30-9) is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment). Note: The GenASIs HiPath IHC Family for Ki67 (30-9) image capture and analysis applications are adjunctive computerassisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer stained for the presence of Ki67 protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. 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 as specified in the instructions for the CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay to assure the validity of the GenASIs HiPath IHC Family for Ki67 (30-9) image capture and analysis scores. The actual correlation of CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary antibody assay to clinical outcome has not been established.
Type of Use (Select one or both, as applicable)
ال 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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Image /page/4/Picture/0 description: The image contains the logo for Applied Spectral Imaging (ASI). The logo features the letters 'ASI' in a stylized font, with a green arc above the letters. Below the letters, the words 'Applied Spectral Imaging' are written in green, followed by the tagline 'Bringing Details to Light' in blue.
510(k) Summar As required by section 807.92(c).
January 15, 2015
510(K) Number A.
B. Purpose for Submission
The proposed ASI's GenASIs HiPath IHC Family, including GenASIs HiPath IHC Family for HER2 (4B5), PR (1E2), ER (SP1) and Ki67 (30-9), is an IVD image capture and image analysis score accessory for assist the qualified pathologist in the consistent assessment of protein expression in immunohistochemical stained histological sections from formalinfixed, paraffin embedded breast cancer tissue.
ASI is hereby preparing this traditional 510(K) submission to show that the proposed ASI's GenASIs HiPath IHC Family is substantially equivalent to the legally marketed predicate devices referred to in paragraph H.
C. Manufacturer and Instrument Name
C.1. Device Name
GenASIs HiPath IHC Family
C.2. Submitter's name
Name: Applied Spectral Imaging Ltd. 2 Ha Carmel St, New Industrial Zone, Yokneam 20691, Israel Tel: (972) 4 6547567, Fax: (972) 4 6547507
C.3. Submission contact person
Ilan Sharon P.O.B. 4414 (A-109), Caesarea 30889, Israel TEL: 972-52-8704904
Type of Test or Tests Performed D.
The GenASIs HiPath IHC Family provides image capture, management, analysis, and viewing of specific immunohistochemically stained slides. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest and is intended for use as an aid to the pathologist in the detection and qualitative measurement of the following tests:
- HER2 protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
5
-
Progesterone receptor (PR) protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRM 114 anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay. The CONFIRM 110 anti-Progesterone Receptor (PR) (1E2) 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). 3. ER (SP1): protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody. The Ventana Medical Systems, Inc. CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of ER status in breast cancer patients (but is not the sole basis for treatment).
-
Ki67 (30-9): protein in formalin-fixed, paraffin-embedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRM " anti-Ki67 (30-9) assay is indicated for use in assessing the proliferative activity of breast cancer tissue. When used with this assay, the GenASIs HiPath IHC Family for Ki67 (30-9) is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment).
E. System Descriptions
Device description:
The GenASIs HiPath IHC Family, including software is designed to assist the qualified pathologist in the consistent assessment in inmmohistochemnically stained histologic sections from formalin-fixed, paraffin-embedded breast cancer tissues. The device consists of a slide capture camera, Microscope, computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Graphic User Interface (GUI).
The GenASIs HiPath IHC Family is an intranet-based, end-to-end, digital pathology software solution that allows pathology laboratories, to acquire, manage, view, analyze, share, and report test results of pathology specimens. Using the GenASIs HiPath IHC Family software the pathologist can view captured images, add annotations, make measurements, perform image analysis and generate reports.
Hardware: A camera based acquisition device designed to captures bright-field microscope digital images of formalin-fixed, paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide acquisition camera, X-Y Stage with holder adaptor for loading glass slides on a microscope and a workstation including a computer, keyboard, mouse and monitor.
Software: The GenASIs HiPath IHC Family software is designed to complement the routine workflow of a qualified pathologist in the review of immunohistochemically stained histologic slides. It allows the user to select fields of view (FOVs) in the digital image for analysis and provides quantitative data on these FOVs to assist with interpretation. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process.
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F. Regulatory Information
Device Classification
| Product Code: | NQN, NOT |
|---|---|
| CFR section: | 21 CFR §864.1860 |
| Regulation name: | Immunohistrochemistry reagents and kits |
| Trade Name: | GenASIs HiPath IHC Family |
| Common Name: | Immunohistrochemistry reagents and kits |
| Classification: | Class II |
Intended Use G.
The GenASIs HiPath IHC Family provides image capture, management, analysis, and viewing of specific immunohistochemically stained slides. It is intended for in vitro diagnostic 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 GenASIs HiPath IHC Family for HER2 (4B5) is for image capture and analysis applications. This particular system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2 protein in formalin-fixed, paraffinembedded breast cancer tissue. This device is an accessory to Ventana Medical Systems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody. The PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
NOTE: The GenASIs HiPath IHC Family for HER2 (4B5) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and semi-quantitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of HER-2/neu receptor protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the quality of the immuohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the PATHWAY® anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody assay used to assure the validity of the GenASIs HiPath IHC Family for HER2 (4B5) image capture and analysis scores. The actual correlation of PATHWAY® anti-HER-2/neu (4B5) to clinical outcome has not been established.
- The GenASIs HiPath IHC Family for PR (1E2) is for image capture and analysis applications. This particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of progesterone receptor (PR) protein in formalinfixed, paraffin-embedded breast cancer tissue. This device is an accessory to Ventana Medical Systems. Inc. CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay. The CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay is indicated for use as an aid in the
7
assessment of breast cancer patients for whom endocrine treatment is being considered (but is not the sole basis for treatment).
Note: The GenASIs HiPath IHC for PR (1E2) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of PR protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody used to assure the validity of the GenASIs HiPath IHC Family for PR (1E2) image capture and analysis scores. The actual correlation of CONFIRMTM anti-PR antibody to clinical outcome has not been established.
- The GenASIs HiPath IHC Family for ER (SP1) is for image capture and analysis applications. The particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of ER (SP1): protein in formalin-fixed, paraffinembedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody. The Ventana Medical Systems, Inc. CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody is indicated for use as an aid in the assessment of ER status in breast cancer patients (but is not the sole basis for treatment).
Note: The GenASIs HiPath IHC Family for ER (SP1) image capture and analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of ER protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the quality of the immuohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to assure the validity of the GenASIs HiPath IHC Family for ER (SP1) image capture and analysis scores. The actual correlation of CONFIRMTM anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary Antibody to clinical outcome has not been established.
- The GenASIs HiPath IHC Family for Ki67 (30-9) is for image capture and analysis applications. The particular system is intended for use as an aid to the pathologist in the detection and qualitative measurement of Ki67 (30-9): protein in formalin-fixed, paraffinembedded breast cancer tissue. This device is an accessory to the Ventana Medical Systems, Inc. CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay. The Ventana Medical Systems, Inc. CONFIRMTM anti-Ki67 (30-9) assay is indicated for use in assessing the proliferative activity of breast cancer tissue. When used with this assay, the GenASIs HiPath IHC Family for Ki67 (30-9) is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment).
Note: The GenASIs HiPath IHC Family for Ki67 (30-9) image capture and analysis
8
applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and qualitative measurement of images from microscope glass slides of breast cancer specimens stained for the presence of Ki67 protein. The pathologist should verify agreement with the Image Analysis software application score by reviewing the glass slide under the microscope. The accuracy of the test results depends on the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary Antibody assay to assure the validity of the GenASIs HiPath IHC Family for Ki67 (30-9) image capture and analysis scores. The actual correlation of CONFIRMTM anti-Ki67 (30-9) Rabbit Monoclonal Primary antibody assay to clinical outcome has not been established.
H. Substantial Equivalence Information
| # | Comparison
parameter | Proposed device:
ASI GenASIs HiPath IHC Family | Predicate device:
VirtuosoTM System |
|----|------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 1 | Owner | Applied Spectral Imaging Ltd. | Ventana Digital Pathology |
| 2 | Legally
distribution
clearance
No. | K..........
Subject to this submission | K111543 - VirtuosoTM System for IHC HER2 (4B5)
K111869 - VirtuosoTM System for IHC PR (1E2)
K130515 - VirtuosoTM System for IHC ER (SP1)
K111755 - VirtuosoTM System for IHC Ki67 (30-9) |
| 3 | Intended use
and
indications
for use. | The GenASIs HiPath IHC Family provides
image capture, management, analysis, and
viewing of specific immunohistochemically
stained slides. It is intended for in vitro
diagnostic 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 GenASIs HiPath IHC Family for
HER2 (4B5) is for image capture and
analysis applications. This particular system
is intended for use as an aid to the
pathologist in the detection and semi-
quantitative measurement of HER2 protein
in formalin-fixed, paraffin-embedded breast
cancer tissue. This device is an accessory to
Ventana Medical Systems, Inc.
PATHWAY® anti-HER2/neu (4B5) Rabbit
Monoclonal Primary Antibody. The
PATHWAY® anti-HER2/neu (4B5) Rabbit
Monoclonal Primary Antibody is indicated
for use as an aid in the assessment of breast
cancer patients for whom HERCEPTIN®
(Trastuzumab) treatment is being
considered.
NOTE: The GenASIs HiPath IHC Family | K111543 - VirtuosoTM System for IHC HER2 (4B5)
The Virtuoso system provides automatic digital
slide creation, management, analysis, and
viewing. It is intended for in vitro diagnostic 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 VirtuosoTM System for HER2 (4B5) is for
digital read and image analysis applications.
This particular system is intended for use as an
aid to the pathologist in the detection and semi-
quantitative measurement of HER2 protein in
formalin-fixed, paraffin-embedded normal and
neoplastic tissue. This device is an accessory to
Ventana Medical Systems, Inc. PATHWAY®
anti-HER2/neu (4B5) Rabbit Monoclonal
Primary Antibody. The PATHWAY® anti-
HER2/neu (4B5) Rabbit Monoclonal Primary
Antibody is indicated for use as an aid in the
assessment of breast cancer patients for whom
HERCEPTIN® (Trastuzumab) treatment is
being considered.
NOTE: The IHC System for HER2 (4B5) digital
read and image analysis applications are
adjunctive computer-assisted methodologies for
the qualified pathologist in the acquisition and |
| # | Comparison
parameter | Proposed device:
ASI GenASIs HiPath IHC Family | Predicate device:
Virtuoso™ System |
| | | for HER2 (4B5) image capture and analysis
applications are adjunctive computer-
assisted methodologies for the qualified
pathologist in the acquisition and semi-
quantitative measurement of images from
microscope glass slides of breast cancer
specimens stained for the presence of HER-
2/neu receptor protein. The pathologist
should verify agreement with the Image
Analysis software application score by
reviewing the glass slide under the
microscope. The accuracy of the test results
depends on the quality of the
immuohistochemical staining. It is the
responsibility of a qualified pathologist to
employ appropriate morphological studies
and controls as specified in the instructions
for the PATHWAY® anti-HER-2/neu
(4B5) Rabbit Monoclonal Primary Antibody
assay used to assure the validity of the
GenASIs HiPath IHC Family for HER2
(4B5) image capture and analysis scores.
The actual correlation of PATHWAY®
anti-HER-2/neu (4B5) to clinical outcome
has not been established. | measurement of images from microscope glass
slides of breast cancer specimens stained for the
presence of HER-2/neu receptor protein. The
pathologist should verify agreement with the
Image Analysis software application score. The
accuracy of the test results depends on the
quality of the immunohistochemical staining. It
is the responsibility of a qualified pathologist to
employ appropriate morphological studies and
controls as specified in the instructions for the
PATHWAY® anti-HER-2/neu (4B5) Rabbit
Monoclonal Primary Antibody assay used to
assure the validity of the iScan System for HER2
4B5 digital read and image analysis scores. The
actual correlation of PATHWAY® anti-HER-
2/neu (4B5) to clinical outcome has not been
established. |
| | 2. | The GenASIs HiPath IHC Family for PR
(1E2) is for image capture and analysis
applications. This particular system is
intended for use as an aid to the pathologist
in the detection and qualitative
measurement of progesterone receptor (PR)
protein in formalin-fixed, paraffin-
embedded breast cancer tissue. This device
is an accessory to Ventana Medical
Systems, Inc. CONFIRMTM anti-
Progesterone Receptor (PR) (1E2) Rabbit
Monoclonal Primary Antibody assay. The
CONFIRMTM anti-Progesterone Receptor
(PR) (1E2) 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 GenASIs HiPath IHC for PR
(1E2) image capture and analysis
applications are adjunctive computer-
assisted methodologies for the qualified
pathologist in the acquisition and qualitative
measurement of images from microscope
glass slides of breast cancer specimens
stained for the presence of PR protein. The | K111869 - Virtuoso™ System for IHC PR (1E2)
The Virtuoso system provides automatic digital
slide creation, management, analysis, and
viewing. It is intended for in vitro diagnostic 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 VirtuosoTM System for PR (1E2) is for
digital read and image analysis applications.
This particular system is intended for use as an
aid to the pathologist in the detection and semi-
quantitative measurement of progesterone
receptor (PR) protein in formalin-fixed, paraffin-
embedded normal and neoplastic tissue. This
device is an accessory to Ventana Medical
Systems, Inc. CONFIRMTM anti-Progesterone
Receptor (PR) (1E2) Rabbit Monoclonal
Primary Antibody assay. The CONFIRMTM anti-
Progesterone Receptor (PR) (1E2) 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 PR (1E2) digital read and image
analysis applications are adjunctive computer- |
| # | Comparison
parameter | Proposed device:
ASI GenASIs HiPath IHC Family | Predicate device:
Virtuoso™ System |
| | | pathologist should verify agreement with
the Image Analysis software application
score by reviewing the glass slide under the
microscope. The accuracy of the test results
depends on the quality of the
immunohistochemical staining. It is the
responsibility of a qualified pathologist to
employ appropriate morphological studies
and controls as specified in the instructions
for the CONFIRM™ anti-Progesterone
Receptor (PR) (1E2) Rabbit Monoclonal
Primary Antibody used to assure the
validity of the GenASIs HiPath IHC Family
for PR (1E2) image capture and analysis
scores. The actual correlation of
CONFIRM™ anti-PR antibody to clinical
outcome has not been established. | assisted methodologies for the qualified
pathologist in the acquisition and measurement
of images from microscope glass slides of breast
cancer specimens stained for the presence of PR
protein. The pathologist should verify agreement
with the Image Analysis software application
score. The accuracy of the test results depends
on the quality of the immunohistochemical
staining. It is the responsibility of a qualified
pathologist to employ appropriate morphological
studies and controls as specified in the
instructions for the CONFIRM™ anti-
Progesterone Receptor (PR) (1E2) Rabbit
Monoclonal Primary Antibody used to assure the
validity of the Virtuoso System for PR (1E2)
digital read and image analysis scores. The
actual correlation of CONFIRM™ anti-PR
antibody to clinical outcome has not been
established. |
| | | 3. The GenASIs HiPath IHC Family for ER
(SP1) is for image capture and analysis
applications. The particular system is
intended for use as an aid to the pathologist
in the detection and qualitative
measurement of ER (SP1): protein in
formalin-fixed, paraffin-embedded breast
cancer tissue. This device is an accessory to
the Ventana Medical Systems, Inc.
CONFIRM™ anti-Estrogen Receptor (ER)
(SP1) Rabbit Monoclonal Primary
Antibody. The Ventana Medical Systems,
Inc. CONFIRM™ anti-Estrogen Receptor
(ER) (SP1) Rabbit Monoclonal Primary
Antibody is indicated for use as an aid in
the assessment of ER status in breast cancer
patients (but is not the sole basis for
treatment). | K130515 - Virtuoso™ System for IHC ER (SP1)
The Virtuoso system provides automated digital
slide creation, management, analysis, and
viewing. It is intended for in vitro diagnostic 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 (SP1) is for
digital read and image analysis applications.
This particular Virtuoso 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 an
accessory to Ventana Medical Systems, Inc.
CONFIRM™ anti-Estrogen Receptor (ER)
(SF1) Rabbit Monoclonal Primary Antibody
assay. The CONFIRM™ anti- ER (SF1) 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 GenASIs HiPath IHC Family for
ER (SP1) image capture and analysis
applications are adjunctive computer-
assisted methodologies for the qualified
pathologist in the acquisition and qualitative
measurement of images from microscope
glass slides of breast cancer specimens
stained for the presence of ER protein. The
pathologist should verify agreement with
the Image Analysis software application
score by reviewing the glass slide under the
microscope. The accuracy of the test results
depends on the quality of the
immunohistochemical staining. It is the
responsibility of a qualified pathologist to
employ appropriate morphological studies
and controls as specified in the instructions | Note: The IHC ER (SP1) 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 specimens stained for the presence of ER
protein. The pathologist should verify agreement
with the Image Analysis software application |
| # | Comparison | Proposed device: | Predicate device: |
| | parameter | ASI GenASIs HiPath IHC Family | Virtuoso"M System |
| | | for the CONFIRMTM anti-Estrogen | score. The accuracy of the test results depends |
| | | Receptor (ER) (SP1) Rabbit Monoclonal | on the quality of the immuohistochemical |
| | | Primary Antibody to assure the validity of | staining. It is the responsibility of a qualified |
| | | the GenASIs HiPath IHC Family for ER | pathologist to employ appropriate morphological |
| | | (SP1) image capture and analysis scores. | studies and controls as specified in the |
| | | The actual correlation of CONFIRMTM | instructions for the CONPIRM™ anti-Estrogen |
| | | anti-Estrogen Receptor (ER) (SP1) Rabbit | Receptor (ER) (SP3) Rabbit Monoclonal
Primary Antibody used to assure the validity of |
| | | Monoclonal Primary Antibody to clinical
outcome has not been established. | the Virtuoso System for IHC ER Digital Read |
| | | | and Image Analysis scores. The actual |
| | | 4. The GenASIs HiPath IHC Family for | correlation of CONFIRM™ anti-Estrogen |
| | | Ki67 (30-9) is for image capture and | Receptor (ER)(SPI) Rabbit Monoclonal |
| | | analysis applications. The particular system | Antibody to clinical outcome has not been |
| | | is intended for use as an aid to the | established. |
| | | pathologist in the detection and qualitative | |
| | | measurement of Ki67 (30-9): protein in | K111755 - Virtuoso™ System for IHC Ki67 (30-9) |
| | | formalin-fixed. paraffin-embedded breast | The Virtuoso system provides automatic digital |
| | | cancer tissue. This device is an accessory to | slide creation, management, analysis, and |
| | | the Ventana Medical Systems, Inc.
CONFIRMTM anti-Ki67 (30-9) Rabbit | viewing. It is intended for in vitro diagnostic use |
| | | Monoclonal Primary Antibody assay. The | as an aid to the pathologist in the display, |
| | | Ventana Medical Systems, Inc. | detection, counting, review and classification of |
| | | CONFIRMTM anti-Ki67 (30-9) assay is | tissues and cells of clinical interest based on |
| | | indicated for use in assessing the | particular morphology, color, intensity, size, |
| | | proliferative activity of breast cancer tissue. | pattern and shape: |
| | | When used with this assay, the GenASIs | The Virtuoso™ System for Ki67 (30-9) is for |
| | | HiPath IHC Family for Ki67 (30-9) is | digital read and image analysis applications. The |
| | | indicated for use as an aid in the assessment | particular system is intended for use as an aid to |
| | | of Ki-67 status in breast cancer patients (but | the pathologist in the detection and semi-
quantitative measurement of Ki67 (30-9): |
| | | is not the sole basis for treatment). | protein in formalin-fixed, paraffin-embedded |
| | | Note: The GenASIs HiPath IHC Family for | normal and neoplastic tissue. This device is an |
| | | Ki67 (30-9) image capture and analysis | accessory to the Ventana Medical Systems, Inc. |
| | | applications are adjunctive computer- | CONFIRM™ anti-Ki67 (30-9) Rabbit |
| | | assisted methodologies for the qualified | Monoclonal Primary Antibody assay. The |
| | | pathologist in the acquisition and qualitative | Ventana Medical Systems, Inc. CONFIRMTM |
| | | measurement of images from microscope | anti-Ki67 (30-9) assay is indicated for use in |
| | | glass slides of breast cancer specimens | assessing the proliferative activity of normal and |
| | | stained for the presence of Ki67 protein. | neoplastic breast tissue. When used with this |
| | | The pathologist should verify agreement
with the Image Analysis software | assay, the Virtuoso™ System for Ki67 (30-9) is |
| | | application score by reviewing the glass | indicated for use as an aid in the assessment of |
| | | slide under the microscope. The accuracy of | Ki-67 status in breast cancer patients (but is not
the sole basis for treatment). |
| | | the test results depends on the quality of the | Note: The IHC Family for Ki67 (30-9) digital |
| | | immunohistochemical staining. It is the | read and image analysis applications are |
| | | responsibility of a qualified pathologist to | adjunctive computer-assisted methodologies for |
| | | employ appropriate morphological studies | the qualified pathologist in the acquisition and |
| | | and controls as specified in the instructions | measurement of images from microscope glass |
| | | for the CONFIRMTM anti-Ki67 (30-9) | slides of breast cancer specimens stained for the |
| | | Rabbit Monoclonal Primary Antibody assay | presence of Ki67 protein. The pathologist should |
| | | to assure the validity of the GenASIs HiPath | verify agreement with the Image Analysis |
| | | IHC Family for Ki67 (30-9) image capture | software application score. The accuracy of the |
| | | and analysis scores. The actual correlation | test results depends on the quality of the |
| | | of CONFIRMTM anti-Ki67 (30-9) Rabbit | inunmohistochemnical staining. It is the |
| # | Comparison | Proposed device: | Predicate device: |
| | parameter | ASI GenASIs HiPath IHC Family | Virtuoso™ System |
| | | Monoclonal Primary antibody assay to
clinical outcome has not been established | responsibility of a qualified pathologist to
employ appropriate morphological studies and
controls as specified in the instructions for the
CONFIRM™ anti-Ki67 (30-9) Rabbit
Monoclonal Primary Antibody assay to assure
the validity of the Virtuoso "M System for Ki67
(30-9) digital read and image analysis scores.
The actual correlation of CONFIRM 104 anti-
Ki67 (30-9) Rabbit Monoclonal Primary
antibody assay to clinical outcome has not been
established. |
| 4 | Application:
IHC HER2
(4B5) | Detection and semi-quantitative
measurement of HER2 protein in formalin-
fixed, paraffin-embedded breast cancer
tissue | Detection and semi-quantitative measurement of
HER2 protein in formalin-fixed, paraffin-
embedded normal and neoplastic tissue |
| 5 | Application:
IHC PR (1E2) | Detection and qualitative measurement of
progesterone receptor (PR) protein in
formalin-fixed, paraffin-embedded breast
cancer tissue. | Detection and semi-quantitative measurement of
progesterone receptor (PR) protein in formalin-
fixed, paraffin-embedded normal and neoplastic
tissue. |
| б | Application:
IHC ER (SP1) | Detection and qualitative measurement of
Estrogen Receptor (ER) protein in formalin-
fixed, paraffin-embedded breast cancer
tissue. | Detection and semi-quantitative measurement of
Estrogen Receptor (ER) protein in formalin-
fixed, paraffin-embedded normal and neoplastic
tissue. |
| 7 | Application:
IHC Ki67 (30-9) | Detection and qualitative measurement of
Ki67 (30-9): protein in formalin-fixed,
paraffin-embedded breast cancer tissue. | Detection and semi-quantitative measurement of
Ki67 (30-9): protein in formalin-fixed, paraffin-
embedded normal and neoplastic tissue. |
| 8 | Specimen
Identification | By the pathologist, according the single
slide label. | Identified by slide label or barcode. |
| 9 | Calibration | Camera White Balance | Tests must be run with nine custom slides
calibrated for the module which can be obtained
from the sponsor. |
| 10 | Ouality
Control | Performed by the operator as part of the
standard operation procedures using slides
with sub-optimal images. | Performed by the operator before releasing the
images to the pathologist for review. Slides with
sub-optimal images will be rescanned |
| 11 | Slide
acquisition/
Capture | CCD high resolution color camera and racks
for loading the glass slides.
Images to be processed selected via
microscope's eyepiece. | Digital slide bright field scanner (Ventana iScan)
and racks for loading glass slides.
Images to be processed selected from the screen
digital read image. |
| 12 | Device
Components | Microscope, CCD color camera, PC,
keyboard, Mouse, Color Monitor, X-Y stage
and rack for loading 1 glass slide. | Digital slide scanner, PC, keyboard, Mouse,
color
Monitor, racks for loading up to 160 glass slides. |
1. Comparison of Predicate devices:
9
10
11
12
13
2. Substantial Equivalence discussion
Similarities:
Intended Use:
The proposed GenASIs HiPath IHC Family and the legally cleared Virtuoso "14 Systems (K111543, K111869, K130515 and K111755) have the same intended use and indications for use for the following: Acquisition, image capture, management, analysis, and viewing. The proposed GenASIs HiPath IHC Family and the legally cleared Virtuoso "" Systems are intended for in vitro diagnostic 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 proposed GenASIs HiPath IHC Family and the legally cleared Virtuoso™ Systems are indicated as an aid to pathologists in the assessment of HER2, PR, ER and Ki67 (30-9) status in breast cancer patients.
Performance:
The proposed GenASIs HiPath IHC Family and the legally cleared Virtuoso™ Systems are designed for the same IVD applications (H1 sections 3 - 6) using similar hardware and software components and similar analysis tools, the pathologist has to select the ROI for the scoring algorithm (H1 sections 7, 8) and calibration and quality control has to be performed to make sure that scoring results are stable (Table 4.3 sections 10, 11).
Technology:
The proposed GenASIs HiPath IHC Family and the legally cleared Virtuoso™ Systems are using similar hardware and software components, designed to complement the routine workflow of a qualified pathologist in the review of IHC stained histological slides (H1 section 12).
Differences:
Intended Use: No difference
Performance:
-
The legally cleared Virtuoso " Systems are using slide scanner for generating the digital slide while the proposed GenASIs HiPath IHC Family is using a color camera to capture and convert the microscope's image to a digital image.
-
Images to be processed selected from Vituoso's screen digital read image, while in the proposed GenASIs HiPath IHC Family images for processing are selected via microscope's eyepiece (H1 section 11).
-
Calibration and quality control processes are different in both systems (H1 sections 10, 11). 4. Legally cleared Virtuoso 100 Systems are designed for multi slide automatic loading, slide label or automatic barcode for specimen identification method must be used while the GenASIs HiPath IHC Family glass slide loading is manual and the pathologist is responsible for the slide identification (H1 section 9).
The effectiveness of the proposed GenASIs HiPath IHC Family calibration and quality control processes were verified and validated during the clinical studies.
14
Technology:
-
The legally cleared Virtuoso "" Systems use a slide scanner for generating the digital slide while the proposed GenASIs HiPath IHC Family use a color camera to capture and convert the microscope's image to a digital image.
-
Acquisition control software and illumination light sources are different and optimized to the acquisition flow and process (H1, sections 10 - 11).
-
The Virtuoso "10 System have additional hardware components; automatic multi slides loader, slides identifier and slide scanner, as opposed to the proposed GenASIs HiPath IHC Family that is using a magnifying microscope for manual slide capture (H1. section 12).
I. Special Control/ Guidance Document Referenced (if applicable)
The following Special Control and guidance documents are used in the preparation of the 510(K) submission:
-
Guidance for Industry "Guidance for Submission of Immunohistochemistry Applications to the FDA", dated June 3 1998.
-
CLSI I/LA28-A2Q:2009 - uality assurance for design control and implementation of immunohistochemistry assays; approved guidelines-second edition. (InVitro Diagnostics).
-
Guidance for Industry and FDA Staff: "Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests"; March 2007.
-
"Guidance for the Content of Premarket Submission for Software Contained in Medical Device", CDRH, May 2005.
-
Guidance for Industry, Clinical Investigators, Institutional Review Boards and Food and Drug Administration Staff, Doc. 1776 dated November 2013
J. Performance Characteristics
The following information of the device performance characteristics are based on ASI testing and experiments, using the following Ventana Medical Systems, Inc probe kits:
- PATHWAY® anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody .
- CONFIRM™ anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary ● Antibody assay
- CONFIRM™ anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Primary . Antibody
- CONFIRM™ anti-Ki67 (30-9) Rabbit Monoclonal Primary antibody assay ●
The user must use the staining process described in Ventana's user instructions for the above mentioned assay kits. Additionally, clinical sensitivity, clinical specificity and clinical cut-off are also related to the above mentioned assay kits (as per user instructions).
The operators shall be aware of limitations derived from the following performance characteristics:
a. Analytical Performance:
The clinical studies were based on comparison to the measures of agreement test of conventional manual evaluation through the microscope eyepieces, performed by
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pathologist that followed the recommendations of the Ventana user insertions for the different panel antibodies and test analysis performed with the proposed GenASIs HiPath IHC Family system, using the same stained slides.
The comparison study was conducted in three clinical sites, by three different pathologists, according to Applied Spectral Imaging's protocol. The study included a total of:
- · HER2/neu (4B5) - 357 stained samples.
- · PR (1E2) · · · · - 385 stained samples.
- · ER (SP1) · - 427 stained samples
- Ki67 (30-9) - 373 stained samples
The agreement rates of the comparison between manual and GenASIs HiPath IHC Family system statistical test results when pooling all three sites tests are:
HER2/neu (4B5)
Pooled Results; Frequency distribution of agreement of Manual versus GenASIs HiPath IHC Family:
| Manual analysis | ||||
|---|---|---|---|---|
| GenASIs HiPath | ||||
| IHC analysis | Negative (0, 1+) | Positive (2+, 3+) | Total | |
| Negative (0, 1+) | 185 | 5 | 190 | |
| Positive (2+, 3+) | 4 | 163 | 167 | |
| Total | 189 | 168 | 357 | |
| Overall Agreement | 97% | |||
| Positive Agreement | 98% | |||
| Negative Agreement | 97% |
PR (1E2)
Pooled Results; Frequency distribution of agreement of Manual versus GenASIs HiPath IHC Family:
| Manual analysis | ||||
|---|---|---|---|---|
| GenASIs HiPath | ||||
| IHC analysis | Negative (10%) | Total | ||
| Negative (≤10%) | 132 | 6 | 138 | |
| Positive (>10%) | 10 | 225 | 235 | |
| Total | 142 | 231 | 373 | |
| Overall Agreement | 96% | |||
| Positive Agreement | 93% | |||
| Negative Agreement | 97% |
Precision/Reproducibility: b.
Repeatability and reproducibility (R&R) studies were conducted to evaluate the variation in the performance of the automatic system between different runs of the same system and same day, between days of the same system and between systems located on different sites. Separate tests were performed for HER2/neu, ER, PR and Ki-67. For each antibody, forty (40) slides were selected, aiming to cover the samples result categories of the intended population.
The one hundred and sixty (160) slides were selected from a known pool as follows:
- · For ER & PR slides were selected from positive, negative and around-cutoff slides to cover the entire clinically relevant range
- · For Ki67 slides were selected from positive, negative slides to cover the entire clinically relevant range
- · For HER2/neu slides were selected from the 4 classes of 0,1+,2+,3+.
All slides were labeled by slide index and antibody type.
Slides were evaluated by three independent pathologists and than were repeatedly evaluated
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by the GenASIs HiPath IHC family device.
A minimal washout time between manual and GenASIs HiPath analysis was 7 days. The precision of manual and system results is reported separately.
The following factors were used for testing GenASIs HighPath family precision:
- Run Each slide is re-evaluated three times on a same system and on a same day. i)
- ii) Day - Each slide is re-evaluated three times on non-consecutive days (at least 5 days apart) on a same system.
- iii) System Each slide is re-evaluated three times using different systems (at least 7 days apart).
HER2/neu (4B5)
The study includes forty (40) sample slides for each antibody, which represent the range of the intended use.
The R&R agreements for positive and negative sample slides analysis were:
| | Average Positive Agreement
(2+, 3+) | Average Negative Agreement
(0, 1+) |
|----------------|----------------------------------------|---------------------------------------|
| Run 1 vs Run 2 | 97.6% | 97.5% |
| Run 1 vs Run 3 | 95.0% | 95.0% |
| Run 2 vs Run 3 | 97.6% | 97.5% |
Between-Run. Within-Day. Within-System:
Between-Day, Within-System:
| | Average Positive Agreement
(2+, 3+) | Average Negative Agreement
(0, 1+) |
|----------------|----------------------------------------|---------------------------------------|
| Day 1 vs Day 2 | 100% | 100% |
| Day 1 vs Day 3 | 97.6% | 97.5% |
| Day 2 vs Day 3 | 97.6% | 97.5% |
Between-Systems:
| | Average Positive Agreement
(2+, 3+) | Average Negative Agreement
(0, 1+) |
|-----------------|----------------------------------------|---------------------------------------|
| Sys 1 vs Syst 2 | 97.6% | 97.5% |
| Sys 1 vs Sys 3 | 97.5% | 97.6% |
| Sys 2 vs Sys 3 | 95.2% | 95.2% |
PR (1E2)
The study include forty (40) sample slides for each antibody, which represent the range of the intended use.
The R&R agreements for positive and negative sample slides analysis were:
Between-Run, Within-Day, Within-System:
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| | Average Positive Agreement
(≥ 1%) | Average Negative Agreement
(10%) | Average Negative Agreement
(≤10%) |
|----------------|--------------------------------------|--------------------------------------|
| Run 1 vs Run 2 | 97.9% | 97.1% |
| Run 1 vs Run 3 | 89.4% | 84.9% |
| Run 2 vs Run 3 | 91.3% | 88.2% |
Between-Day, Within-System:
| | Average Positive Agreement
(>10%) | Average Negative Agreement
(≤10%) |
|----------------|--------------------------------------|--------------------------------------|
| Day 1 vs Day 2 | 95.8% | 93.8% |
| Day 1 vs Day 3 | 95.8% | 93.8% |
| Day 2 vs Day 3 | 95.8% | 93.8% |
Between-Systems:
| Average Positive Agreement | Average Negative Agreement | |
|---|---|---|
| (>10%) | ( |