(159 days)
Not Found
No
The description mentions image analysis and classification based on color, size, and shape, which are standard image processing techniques, but does not mention AI, ML, or related concepts like neural networks or deep learning. The performance studies focus on agreement and reproducibility, not metrics typically associated with AI/ML model evaluation.
No.
The device is an accessory to aid pathologists in the semi-quantitative measurement of HER2/neu in breast cancer tissue, acting as an aid in assessment for treatment consideration; it does not directly treat or prevent a disease.
Yes
The device is intended to aid a pathologist in the semi-quantitative measurement of HER2/neu (c-erbB-2) in breast cancer tissue, which is a diagnostic activity to assess patients for potential Herceptin® (Trastuzumab) treatment.
Yes
The device is explicitly described as a "standalone software application" and the required hardware (computer, digitizing equipment) is listed as "required but not provided". The 510(k) focuses on the software's functionality and performance in analyzing digitized images.
Based on the provided information, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is an "accessory to the Dako HercepTest® to aid a pathologist in semi-quantitative measurement of HER2/neu (c-erbB-2) in Formalin-fixed, paraffin-embedded breast cancer tissue." This directly relates to the examination of specimens derived from the human body (tissue) to provide information for diagnostic purposes (assessing breast cancer patients for Herceptin treatment).
- Specimen Type: The device analyzes "Formalin-fixed, paraffin-embedded breast cancer tissue," which is a human specimen.
- Diagnostic Purpose: The information provided by the device (semi-quantitative measurement of HER2/neu) is used to "aid in the assessment of breast cancer patients for whom Herceptin® (Trastuzumab) treatment is being considered." This is a clear diagnostic application.
- Accessory to an IVD: The device is described as an "accessory to the Dako HercepTest®," which is itself an IVD used for HER2 testing. Accessories to IVDs that are intended to be used with the IVD to perform its intended function are also considered IVDs.
The fact that it processes digitized images of microscope slides and provides a suggested score to a pathologist for their final interpretation does not negate its IVD status. It is still providing information derived from a human specimen for a diagnostic purpose.
N/A
Intended Use / Indications for Use
BioImagene PATHIAM is intended for use as an accessory to the Dako HercepTest® to aid a pathologist in semi-quantitative measurement of HER2/neu (c-erbB-2) in Formalin-fixed, paraffin-embedded breast cancer tissue. When used with the Dako HercepTest it is indicated as an aid in the assessment of breast cancer patients for whom Herceptin® (Trastuzumab) treatment is being considered.
NOTE: The actual correlation of the Dako HercepTest to Herceptin clinical outcome has not been established.
Product codes
NOT
Device Description
PATHIAM software is a standalone software application that will work on a system with the following features required but not provided:
Computer
- Processor: 2.4 GHz, Pentium IV equivalent
- Memory: 512 MB RAM
- Operating System: Windows 2000 or later
- Hard Drive: minimum 100MB for software installation, 20GB for image storage
- LAN connectivity, minimum 100 MBPS (recommended), support for USB interface, support for HTTP, TCP/IP protocols (using the Operating system)
- High Speed Graphic Accelerator Card (1024 X 768)
- 17" High resolution display monitor
- 24 bit color depth
- Font Setting: Small font (DPI setting: 96 DPI)
Digitizing Equipment: Camera
- Resolution: at least 2048 x 1536 pixels
- Frame rate: 20 fps@1200 x 768 resolution (6 fps @ 2048 x 1536 resolution)
- Sampling Frequency of 6.26 square/um
- Compression format: JPEG 2000, BMP, TIFF, JPEG
- Color: 24-bit (R. G. B)
- Connection to computer
Digitizing Equipment: Digital Side Scanner
- Input Format: 25X75mm microscope slides
- Resolution: 54,000 pixel/inch with 20X objective
- Method: Line-scanning
- File Format: TIFF/JPEG2000; compliant with TIFF 6.0 standard.
- Color: 24-bit (R.G. B)
- Connectivity: 100/1000 MBPS Ethernet
- Compression format: JPEG 2000, BMP, TIFF, JPEG
The software allows both archiving of the digital image, and semi quantitative analysis of extent and intensity of stained tissue, providing the pathologist with an aid to interpretation of level of expression of Her2/neu in breast cancer tissue. The pathologist is presented with a digital image of the tissue section and a suggested staining score (0 to 3). The pathologist then makes an assessment of the digital image and reports his/her score.
Mentions image processing
The imaging software is intended to detect and classify cells of clinical interest by analyzing digitized images of microscope slides based on recognition of cellular objects of particular color, size and shape. The software can be used with a computer and image digitizer with features specified in the labeling.
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Microscope slides, Digital image
Anatomical Site
Breast cancer tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Pathologist
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
Not Found
Summary of Performance Studies
The PATHIAM software was tested for between-laboratory reproducibility by three different pathologists who analyzed images of the same set of 176 stained breast cancer tissue specimens using three different imaging systems across three different laboratories in the US. One laboratory used a microscope with a camera, and two used different models of digital whole slide scanners. The initial score distribution for these samples was 1/6 for score 0, 1/3 for score 1, 1/3 for score 2, and 1/6 for score 3.
Key results:
-
Between-Lab Agreement for Raw PATHIAM- Scores: Ranged from 94% to 95%.
- Lab 1 vs Lab 2: 95% (95% CI: 91-98)
- Lab 1 vs Lab 3: 94% (95% CI: 89-96)
- Lab 2 vs Lab 3: 94% (95% CI: 89-97)
-
Between-Lab Agreement for Pathologist Assisted by PATHIAM Scores: Ranged from 81% to 96%.
- Lab 1 vs Lab 2: 96% (95% CI: 92-98)
- Lab 1 vs Lab 3: 81% (95% CI: 75-87)
- Lab 2 vs Lab 3: 81% (95% CI: 74-89)
-
Between-Lab Agreement for Manual Scores (Microscope Assessment Only): Ranged from 76% to 97%.
- Lab 1 vs Lab 2: 97% (95% CI: 93-99)
- Lab 1 vs Lab 3: 76% (95% CI: 69-82)
- Lab 2 vs Lab 3: 78% (95% CI: 71-84)
-
Percent Agreement Between PATHIAM-Assisted and Manual Scores (within each lab):
- Lab 1: 81% (95% CI: 75-87)
- Lab 2: 84% (95% CI: 78-89)
- Lab 3: 82% (95% CI: 76-88)
-
Percent Agreement between PATHIAM raw scores and Manual Scores (within each lab):
- Lab 1: 81% (95% CI: 74-86)
- Lab 2: 83% (95% CI: 77-88)
- Lab 3: 78% (95% CI: 71-84)
Conclusion: The agreement of manual scores compared to PATHIAM raw scores (Table 5) is more consistent than the inter-pathologist comparison of manual scores (Table 3). Consistency is improved when the PATHIAM score assists the pathologist (Table 2). The comparison of PATHIAM raw scores across the three different setups in three different laboratories is very good (Table 1).
Key Metrics
% Overall Agreement, 95% Confidence Interval (Exact)
Predicate Device(s)
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.
0
KO62756
FEB 2 0 2007
510(K) SUMMARY OF SAFETY AND EFFECTIVENESS
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92(c).
Submitted by: BioImagene, Inc. 1601 S. De Anza Blvd. Suite 212 Cupertino, CA 95014 United States
Contact Person Anna Longwell Longwell and Associates 1900 Embarcadero Road, Suite 107 Palo Alto. CA 94303 Tel 650.213.9162 FAX 650.213.9164 anna.longwell(@fdclaw.com
Date Summary Prepared: 25 August 2006 Date Summary Revised: 11 January 2007
Trade Name: PATHIAM Image Analysis Software for Her2/neu
Classification Name: Unknown
Device Description:
PATHIAM software is a standalone software application that will work on a system with the following features required but not provided:
Computer
- . Processor: 2.4 GHz, Pentium IV equivalent
- Memory: 512 MB RAM .
- Operating System: Windows 2000 or later .
- Hard Drive: minimum 100MB for software installation, 20GB for image . storage
- . LAN connectivity, minimum 100 MBPS (recommended), support for USB interface, support for HTTP, TCP/IP protocols (using the Operating system)
- High Speed Graphic Accelerator Card (1024 X 768) .
- 17" High resolution display monitor .
- 24 bit color depth .
- Font Setting: Small font (DPI setting: 96 DPI) .
Digitizing Equipment: Camera
- Resolution: at least 2048 x 1536 pixels .
- . Frame rate: 20 fps@1200 x 768 resolution (6 fps @ 2048 x 1536 resolution)
- . Sampling Frequency of 6.26 square/um
1
- . Compression format: JPEG 2000, BMP, TIFF, JPEG
- Color: 24-bit (R. G. B) .
- Connection to computer
Digitizing Equipment: Digital Side Scanner
- Input Format: 25X75mm microscope slides .
- . Resolution: 54,000 pixel/inch with 20X objective
- . Method: Line-scanning
- . File Format: TIFF/JPEG2000; compliant with TIFF 6.0 standard.
- . Color: 24-bit (R.G. B)
- Connectivity: 100/1000 MBPS Ethernet .
- . Compression format: JPEG 2000, BMP, TIFF, JPEG
The software allows both archiving of the digital image, and semi quantitative analysis of extent and intensity of stained tissue, providing the pathologist with an aid to interpretation of level of expression of Her2/neu in breast cancer tissue. The pathologist is presented with a digital image of the tissue section and a suggested staining score (0 to 3). The pathologist then makes an assessment of the digital image and reports his/her score.
Indications for Use:
BioImagene PATHIAM is intended for use as an accessory to the Dako HercepTest® to aid a pathologist in semi-quantitative measurement of HER2/neu (c-erbB-2) in Formalin-fixed, paraffin-embedded breast cancer tissue. When used with the Dako HercepTest it is indicated as an aid in the assessment of breast cancer patients for whom Herceptin® (Trastuzumab) treatment is being considered.
NOTE: The actual correlation of the Dako HercepTest to Herceptin clinical outcome has not been established.
Predicate Devices:
Software Her2/neu application of ChromaVision Medical Systems, Inc. Automated Cellular Imaging System (ACIS) for Her2/neu, K032113
Performance
- a. Between laboratory reproducibility: PATHIAM software was tested by three different pathologists, who analyzed images of the same set of 176 stained breast cancer tissue specimens using three different imaging systems in three different laboratories located at three different sites in the US. One laboratory used a microscope with a camera, and two used different models of digital whole slide scanners. The score distribution for these samples, as determined initially, was 1/6 of samples score 0, 1/3 of samples score 1, 1/3 of samples score 2, and 1/6 of samples score 3.
Overall agreement for the PATHIAM values between labs ranged from 94% to 95% (Table 1). For pathologist assisted by PATHIAM, overall agreement
2
between labs was 81% to 96% (Table 2). Overall agreement between laboratories for a manual (microscope assessment only) value ranged from 76% to 97% (Table 3).
| Lab # vs. Lab# | % Overall
Agreement | 95% Confidence Interval
(Exact) |
|----------------|------------------------|------------------------------------|
| 1 v 2 | 95 | 91-98 |
| 1 v 3 | 94 | 89-96 |
| 2 v 3 | 94 | 89-97 |
Table 1. Between-Lab Agreement for Raw PATHIAM- Scores, HercepTest®stained Breast Tissue
Table 2. Between-Lab Agreement for Pathologist Assisted by PATHIAM Scores, HercepTest-stained Breast Tissue
| Lab # vs. Lab# | % Overall
Agreement | 95% Confidence Interval
(Exact) |
|----------------|------------------------|------------------------------------|
| 1 v 2 | 96 | 92-98 |
| 1 v 3 | 81 | 75-87 |
| 2 v 3 | 81 | 74-89 |
Table 3. Between-Lab Agreement for Manual Scores, HercepTest-stained Breast Tissue
| Lab # vs. Lab # | % Overall
Agreement | 95% Confidence Interval
(Exact) |
|-----------------|------------------------|------------------------------------|
| 1 v 2 | 97 | 93-99 |
| 1 v 3 | 76 | 69-82 |
| 2 v 3 | 78 | 71-84 |
- b. Comparison with manual (microscope assessment only) Her2-neu scores were obtained for those same breast cancer tissues from a review of PATHIAM values by the same three trained pathologists, who viewed both the digital images and the score provided by the software, and then selected an appropriate Her2-neu tissue score (0 to 3). One week later, the same pathologist read the same slides manually, using an optical microscope. The table shows the comparison.
3
| Lab # | % Overall
Agreement | 95% Confidence Interval
(Exact) |
|-------|------------------------|------------------------------------|
| 1 | 81 | 75-87 |
| 2 | 84 | 78-89 |
| 3 | 82 | 76-88 |
Table 4. Percent Agreement Between PATHIAM-Assisted and Manual Scores, HercepTest®-stained Breast Tissue
| Table 5. Percent Agreement between PATHIAM raw scores and Manual Scores, | |
|---|---|
| HercepTest-stained breast Tissue |
| Lab # | % Overall
Agreement | 95% Confidence Interval
(Exact) |
|-------|------------------------|------------------------------------|
| 1 | 81 | 74-86 |
| 2 | 83 | 77-88 |
| 3 | 78 | 71-84 |
- c. Conclusion: It can be seen that the agreement of the manual scores compared to the PATHIAM raw scores (Table 5) is more consistent than the inter-pathologist comparison of manual scores (Table 3). Consistency is improved when the PATHIAM score assists the pathologist in their interpretation (Table 2). The comparison of PATHIAM raw scores across the three different setups in three different laboratories is very good (Table 1). Differences may be due to the selection by the pathologists of different fields of view for the analyses.
- d. Specificity, sensitivity and interferences are described in the HercepTest package insert.
- Substantial equivalence: Table 6 shows a comparison of attributes between e. PATHIAM and the predicate
| Attribute | ACIS Her2/neu software
component | PATHIAM |
|--------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended use | The imaging software is
intended to detect and
classify cells of clinical
interest by analyzing digital
images of microscope slides
based on object
identification of cellular | Same |
| Indications for use | objects of particular
intensity, shape, size and
color. The software can be
used with a computer and
image digitizer with
features specified in the
labeling
As an accessory to an assay
which is indicated as an aid
in the assessment of breast
cancer patients for whom
Herceptin® treatment is
considered | As an accessory to the Dako
HercepTest® to aid a
pathologist in semi-
quantitative measurement of
HER2/neu (c-erbB-2) in
Formalin-fixed, paraffin-
embedded breast cancer
tissue.
When used with the Dako
HercepTest it is indicated as
an aid in the assessment of
breast cancer patients for
whom Herceptin®
(Trastuzumab) treatment is
being considered. |
| Specimen Type | Formalin-fixed, paraffin-
embedded specimens
stained by
immunohistochemistry
reagent for Her2/neu | Same |
| Image Analysis System | Histologic observation by a
pathologist through a
controlled
microscope/digital camera
combination | Histologic observation by a
pathologist through a
specified microscope/digital
camera combination or slide
scanner |
| Method of Cell Detection | Colorimetric pattern
recognition by microscopic
examination of prepared
cells by size, shape, hue
and intensity as observed by
a computer-assisted
microscope and by visual
observation by a health care
professional | Object identification of a
digitized field of view of a
pathology slide, using size,
shape, color and intensity as
observed by a software and
by visual observation of the
digitized image by a health
care professional. |
| Hardware components | Computer, microscope,
color monitor, keyboard,
automatic storage of
acquired images | Required but not provided:
computer, either
microscope with digitizing
camera or slide scanner, |
| | | keyboard, mouse, hi-
resolution color monitor,
and hard drive for storage. |
| Assay used | DAKO HercepTest | Same |
Table 6. Comparison to Predicate Devices to Support Substantial Equivalence Determination
4
5
- f. Standards Employed: None under Section 514
- EDA Guidance Guidance for the Content of Premarket Submissions for Software g. contained in Medical Devices, May 11, 2005
6
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" arranged around the perimeter. Inside the circle is a stylized symbol featuring three parallel lines that curve and flow together, resembling a human figure or a flame.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
BioImagene, Inc. c/o Ms. Anna Longwell Longwell and Associates 1900 Embarcadero Rd Suite 107 Palo Alto, CA 94303
FEB 2 0 2007
Re: K062756
Trade/Device Name: PATHIAMTM Imaging Software for Her2/neu Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry Reagents and Kits Regulatory Class: Class II Product Code: NOT Dated: February 12, 2007 Received: February 13, 2007
Dear Ms. Longwell:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The
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Page 2 -
FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Robert H. Becker/
Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
8
Indications for Use
510(k) Number (if known): K062756
్ర
Device Name: PATHIAM™ Imaging software for Her2/neu
Biolmagene PATHIAM is intended for use as an accessory to Indications For Use: the Dako HercepTest® to aid a pathologist in semi-quantitative measurement of HER2/neu (c-erbB-2) in Formalin-fixed, paraffin-embedded breast cancer tissue. When used with the Dako HercepTest it is indicated as an aid in the assessment of breast cancer patients for whom Herceptin® (Trastuzumab) treatment is being considered. NOTE: The actual correlation of the Dako HercepTest to Herceptin clinical outcome has not been established.
The imaging software is intended to detect and classify cells of Intended Use: clinical interest by analyzing digitized images of microscope slides based on recognition of cellular objects of particular color, size and shape. The software can be used with a computer and image digitizer with features specified in the labeling.
Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Mana mchan
Division Sian-Off
Page 1 of 1
Office of In Vitro Dlagnostic Device Evaluation and Safety
510(k) Ko 627356
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