(344 days)
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for in vitro diagnostic use as an aid to pathology professionals for creating, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalin-fixed, paraffin-embedded (FFPE) tissue sections stained with the Dako HercepTest™.
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in digital images of FFPE breast cancer tissue immunohistochemically stained with the Dako HercepTest™ and viewed on a computer monitor.
The Dako HercepTest™ is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended to aid pathology professionals in creating, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalin-fixed, paraffin-embedded (FFPE) tissue sections stained with the Dako HercepTest™.
The system is composed of the following components:
- VL4 Scanner: A hardware device that captures and compresses bright field images of tissue samples.
- Data and Workflow Infrastructure: A set of networked applications which enables case data entry, acquisition, indexing, storage and acceptance of digital images, workflow management, and retrieval of case and image data.
- Histology Workstation: The application which permits the histologist to review or enter case data and check quality of scanned images.
- Pathology Workstation: The application which allows the pathologist to retrieve case data and review and annotate slide images.
Hardware:
The Omnyx™ VL4 scanner is an automated imaging system that can be loaded with up to 4 slides at a time. The VL4 Scanner outputs its images and metadata to the Omnyx Digital Archive, which receives and stores the images and data.
Software:
The Omnyx software is composed of 1) the VL4 scanner software which performs tissue identification, scan planning, focusing, image acquisition, stitching and compression of digital slide images and sends them to the Digital Archive and 2) the DPS software that manages the Histologist and Pathologist workstation functions, image viewer, workflow service, database, interface engine, APLIS service, digital archive, image store and the administrator client application.
Here's a breakdown of the acceptance criteria and the study that proves the Omnyx Manual Read of the Digital HER2 Application meets these criteria, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the clinical comparison and precision/reproducibility studies, aiming to demonstrate non-inferiority to manual microscopy and reliable performance. The studies evaluate agreement between different modalities (manual vs. digital) and within identical modalities but different readers/days/scanners.
| Category | Acceptance Criteria (Implicit) | Reported Device Performance (Summary) |
|---|---|---|
| Inter-Reader/Intra-Modality (MM) | High percent agreement between pathologists reading on conventional manual microscopes. | Trichotomous: Agreements ranged from 80.5% (74%-85%) to 88.0% (83%-92%).Binary: Overall Agreements ranged from 86.2% (81%-90%) to 93.5% (89%-96%). APA and ANA were similarly high. |
| Inter-Reader/Intra-Modality (M-WSI) | High percent agreement between pathologists reading on the Omnyx IDP system (digital WSIs). | Trichotomous: Agreements ranged from 64.4% (57%-71%) to 87.2% (82%-91%).Binary: Overall Agreements ranged from 73.9% (67%-80%) to 89.9% (85%-93%). APA and ANA were similarly high. (Note: One specific pairing showed a slightly lower agreement compared to MM). |
| Inter-Modality/Intra-Reader (MM vs. M-WSI) | High percent agreement for individual pathologists when comparing their manual reads to their digital reads. This demonstrates that the digital system does not introduce significant reading discrepancies. | Trichotomous: Not explicitly reported as a single agreement metric, but individual pathologist data is provided. Implicitly high agreement is claimed.Binary: Overall Percent Agreements ranged from 89.4% (79%-89%) to 93.0% (88%-96%). NPA and PPA were similarly high. |
| Intra-Reader/Inter-Day (M-WSI) | High precision/reproducibility for individual pathologists when reading the same digital slides on different days. | Trichotomous: Agreements ranged from 62.5% (47%-76%) to 97.5% (87%-100%) across three pathologists and three reads. Pathologist 1 had lower scores (62.5%, 77.5%, 85.0%) while Pathologists 2 and 3 had higher scores (all >90%).Binary: Overall Agreements ranged from 70.0% (55%-82%) to 100.0% (91%-100%). NPA and PPA were similarly high, generally consistent with trichotomous results for each pathologist. |
| Inter-Scanner/Intra-Reader (ROIs) | High agreement between ROIs sourced from different scanners when read by the same pathologist, indicating scanner consistency. | Trichotomous: Agreements ranged from 88.8% (80%-94%) to 95.0% (88%-98%) for pairwise scanner comparisons. This indicates "very high reproducibility among scanners." |
2. Sample Size Used for the Test Set and Data Provenance
- Clinical Comparison (MM vs. M-WSI):
- Sample Size: 200 breast cancer cases (samples stained with Dako HercepTest™ and controls).
- Data Provenance: Not explicitly stated, but the study was conducted comparing reads from conventional manual microscopes and the Omnyx IDP system, suggesting it was based on existing clinical samples. It is not specified if the data was retrospective or prospective, or the country of origin.
- Precision & Reproducibility (Intra-Reader/Inter-Day):
- Sample Size: 40 HercepTest™ stained slides.
- Data Provenance: Not explicitly stated (retrospective/prospective, country of origin).
- Precision & Reproducibility (Inter-Scanner/Intra-Reader):
- Sample Size: 80 regions of interest (ROIs) extracted from 40 HercepTest™ slides, with an even distribution of score categories.
- Data Provenance: The three scanners were located in "three different laboratory locations within GE Healthcare and operated by three independent operators." This indicates multi-site internal data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Clinical Comparison (MM vs. M-WSI):
- Number of Experts: Four (4) pathologists.
- Qualifications: Not explicitly stated beyond "pathologists."
- Ground Truth: For the inter-reader/intra-modality analysis, the comparisons are between pathologists, so no single "ground truth" is established by an expert panel; rather, concordance between experts is assessed. For the inter-modality/intra-reader comparison, the glass slide read by each pathologist serves as their imperfect reference for their digital read.
- Precision & Reproducibility (Intra-Reader/Inter-Day):
- Number of Experts: Three (3) pathologists.
- Qualifications: Not explicitly stated beyond "pathologist."
- Ground Truth: Not applicable in this context; the study assesses a single pathologist's reproducibility over time, not against an external "ground truth."
- Precision & Reproducibility (Inter-Scanner/Intra-Reader):
- Number of Experts: A single pathologist.
- Qualifications: Not explicitly stated beyond "a single pathologist."
- Ground Truth: The manual scores by this single pathologist served as the reference for comparing ROIs from different scanners.
4. Adjudication Method for the Test Set
- Clinical Comparison (MM vs. M-WSI): No formal adjudication method is mentioned for establishing a single "ground truth" across readers. The study focuses on pairwise agreement between pathologists and agreement of an individual pathologist across modalities. For the binary agreement calculations, "neither pathologist can be considered a reference in each pairwise reader comparison," so Average Negative Agreement (ANA) and Average Positive Agreement (APA) are used instead of traditional sensitivity/specificity against a single ground truth.
- Precision & Reproducibility (Intra-Reader/Inter-Day): Not applicable; this study assessed intra-reader variability over time.
- Precision & Reproducibility (Inter-Scanner/Intra-Reader): A single pathologist established the scores for the ROIs, effectively acting as the adjudicator/reference for scanner comparisons.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed in the sense of AI assistance improving human reader performance.
- The study design focused on demonstrating that the digital platform (Omnyx IDP System with manual reading) is substantially equivalent to manual microscopy. It evaluates the concordance between pathologists using traditional manual methods and pathologists using the digital system.
- The device described is the "Omnyx Manual Read of the Digital HER2 Application," implying no AI algorithm for automated scoring or triage that would "assist" the human reader. The pathologist still performs the interpretation manually, but on digital images rather than glass slides.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- No. The device is explicitly for "Manual Read of the Digital HER2 Application." Its intended use states it is "an aid to pathology professionals" and "an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu...viewed on a computer monitor." This indicates it's a tool for manual interpretation of digital images, not an automated algorithm for standalone performance.
7. The Type of Ground Truth Used
- Clinical Comparison (MM vs. M-WSI):
- For inter-reader/intra-modality comparisons, concordance between pathologists serves as the metric, not an external "ground truth."
- For inter-modality/intra-reader comparisons ("MM vs. M-WSI"), the glass slide read by each pathologist was used as their respective imperfect reference. This is explicitly stated, indicating that it's considered an imperfect reference rather than a definitive, independently verified ground truth.
- Precision & Reproducibility (Inter-Scanner/Intra-Reader): The 80 ROIs were "manually scored by a single pathologist based on the Dako HercepTest™ scoring guidelines." This single pathologist's score serves as the ground truth for evaluating inter-scanner agreement.
8. The Sample Size for the Training Set
- The document does not explicitly mention a "training set" or "validation set" in the context of an AI algorithm learning to interpret images.
- Since this device is a "Manual Read" application that facilitates human interpretation of digital slides, rather than an AI algorithm for automated diagnosis, the concept of a training set as typically understood for AI models is not applicable or discussed. The studies describe performance evaluation sets for human readers.
9. How the Ground Truth for the Training Set was Established
- As mentioned above, a "training set" for an AI model is not discussed in this document, as the device is for manual interpretation of digital slides. Therefore, the establishment of ground truth for such a set is not applicable here.
{0}------------------------------------------------
K13/140
APR 0 1 2014
510(k) Summary for the Omnyx, LLC. Omnyx Manual Read of the Digital HER2 Application
SUBMITTER/510(K) HOLDER 1.
Omnyx, LLC 1251 Waterfront Place Pittsburgh, PA 15222
Contact Person: Michael C. Montalto, Ph.D. Telephone: 732-457-8135
CONSULTANT/CONTACT 2.
Aptiv Solutions 62 Forest Street Suite 300 Marlborough, MA 01752 Telephone: (main) 508-597-6000 (direct) 508-835-1688 508-597-5789 Facsimile:
Primary Contact: Gail E. Radcliffe, Ph.D. Date Prepared: April 19, 2012
DEVICE NAME 3.
| Proprietary Name: | Omnyx Manual Read of the Digital HER2 Application |
|---|---|
| Common/Usual Name: | Digital Pathology Device |
| Classification: | Class II |
| Product Code: | OEO (automated digital image manual interpretation microscope) |
PREDICATE DEVICES 4.
{1}------------------------------------------------
5. DEVICE DESCRIPTION
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended to aid pathology professionals in creating, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalin-fixed, paraffin-embedded (FFPE) tissue sections stained with the Dako HercepTest™.
The system is composed of the following components:
- · VL4 Scanner: A hardware device that captures and compresses bright field images of tissue samples.
- · Data and Workflow Infrastructure: A set of networked applications which enables case data entry, acquisition, indexing, storage and acceptance of digital images, workflow management, and retrieval of case and image data.
- · Histology Workstation: The application which permits the histologist to review or enter case data and check quality of scanned images.
- · Pathology Workstation: The application which allows the pathologist to retrieve case data and review and annotate slide images.
Hardware:
The Omnyx™ VL4 scanner is an automated imaging system that can be loaded with up to 4 slides at a time. The VL4 Scanner outputs its images and metadata to the Omnyx Digital Archive, which receives and stores the images and data.
Software:
The Omnyx software is composed of 1) the VL4 scanner software which performs tissue identification, scan planning, focusing, image acquisition, stitching and compression of digital slide images and sends them to the Digital Archive and 2) the DPS software that manages the Histologist and Pathologist workstation functions, image viewer, workflow service, database, interface engine, APLIS service, digital archive, image store and the administrator client application.
{2}------------------------------------------------
Principles of Operation:
FFPE tissue sections are stained with the Dako HercepTest™ according to the package insert. Slides are then scanned and digitized using the Omnyx VL4 Scanner. Whole slide images are transferred automatically to the Omnyx Digital Archive (DA) where they are indexed and stored. The Workflow Server contains patient information. These files are then accessed using the Histology Workstation or the Pathologist Workstation. The Histology Workstation is used by histologists or other lab professionals to perform quality checks on scanned slides, confirm that IHC slides/case associations are correct and order re-cuts and re-stains. It also enables the histologist to enter case data manually. The Pathologist Workstation enables the pathologist to flag significant cases and regions of interest. It also allows the pathologist to review the digital HercepTest™ IHC whole slide image (WSI) via the Omnyx Image Viewer and is used by the pathologist for functions such as annotating images and making measurements.
6. INDICATIONS FOR USE/ INTENDED USE
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for in vitro diagnostic use as an aid to pathology professionals for creating, managing, storing, annotating, measuring, and viewing digital Whole Slide Images (WSI) from formalinfixed, paraffin-embedded (FFPE) tissue sections stained with the Dako HercepTest™.
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in digital images of FFPE breast cancer tissue immunohistochemically stained with the Dako HercepTest™ and viewed on a computer monitor.
The Dako HercepTest™ is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
{3}------------------------------------------------
7. SUMMARY OF TECHNOLOGICAL CHARACTERISTICS COMPARED TO THE PREDICATE DEVICES
The following table summarizes the similarities and differences between the Omnyx Manual Read of the Digital HER2 Application and the predicate devices Aperio ScanScope XT System and Virtuoso™ IHC HER2.
| Proposed Device | Predicate | Predicate | |
|---|---|---|---|
| Omnyx Manual Read of the | Aperio ScanScope XT System | Virtuoso™ IHC HER2 | |
| Comparators | Digital HER2 Application | (K071671) | (K111543) |
| Intended use | The Omnyx Manual Read ofthe Digital HER2Application on the OmnyxIDP System is intended forin vitro diagnostic use as anaid to pathologyprofessionals for creating,receiving, managing, storing,annotating, measuring, andviewing digital Whole SlideImages (WSI) fromformalin-fixed, paraffin-embedded (FFPE) tissuesections stained with theDako HercepTest™. | The ScanScope system is anautomated digital slide creation,management, viewing andanalysis system. It is intendedfor in vitro diagnostic use as anaid to the pathologist in thedisplay, detection, counting andclassification of tissues and cellsof clinical interest based onparticular color, intensity, size,pattern and shape. | This device is intended for in vitro(IVD) use.The Virtuoso System providesautomated digital slide creation,management, analysis, and viewing. Itis intended for IVD use as an aid to thepathologist in the display, detection,counting, review and classification oftissues and cells of clinical interest basedon particular morphology, color,intensity, size, pattern and shape. |
| The Omnyx Manual Readof the Digital HER2Application on the OmnyxIDP System is intended foruse as an aid to thepathologist in the detectionand semi-quantitativemeasurement of HER2/neu(c-erbB-2) in digital imagesof FFPE breast cancer tissueimmunohistochemicallystained with the DakoHercepTest™ and viewed ona computer monitor. DakoHercepTest™ is indicatedfor use as an aid in theassessment of breast cancerpatients for whomHERCEPTIN®(Trastuzumab) treatment isbeing considered. | The IHC HER2 Manual Read ofa Digital Slide application isintended for use as an aid to thepathologist in the detection andsemi-quantitative measurementof HER2/neu (c-erbB-2) informalin-fixed, paraffin-embedded normal and neoplastictissue immunohistochemicallystained for HER-2 receptors on acomputer monitor. HER2 resultsare indicated for use as an aid inthe management, prognosis andprediction of therapy outcomes inbreast cancer. | The Virtuoso™ System for IHC HER2(4B5) is for digital read and imageanalysis applications. This particularVirtuoso system is intended for use as anaid to the pathologist in the detectionand semi-quantitative measurement ofHER2 protein in formalin-fixed,paraffin-embedded normal andneoplastic tissue. This device is anaccessory to the Ventana MedicalSystems, Inc. PATHWAY® anti-HER2/neu (4B5) Rabbit MonoclonalPrimary Antibody. The PATHWAY®anti-HER2/neu (4B5) RabbitMonoclonal Primary Antibody isindicated for use as an aid in theassessment of breast cancer patients forwhom HERCEPTIN® (Trastuzumab)treatment is being considered.Note: The IHC HER2 (4B5) DigitalRead and Image Analysis applicationsare adjunctive computer-assistedmethodologies for the qualifiedpathologist in the acquisition andmeasurement of images frommicroscope glass slides of breast cancer | |
| The IHC HER2 Manual Read ofa Digital Slide application isintended for use as an accessoryto the Dako HercepTest™ to aidin the detection and semi-quantitative measurement ofHER2/neu (c-ebB-2) in formalin-fixed, paraffin-embedded normaland neoplastic tissueimmunohistochemically stainedfor HER-2 receptors on acomputer monitor. When usedwith the Dako HercenTest, it is | specimens stained for the presence of | ||
| Proposed Device | Predicate | Predicate | |
| Omnyx Manual Read of the | Aperio ScanScope XT System | Virtuoso™ IHC HER2 | |
| Comparators | Digital HER2 Application | (K071671) | (K111543) |
| indicated for use as an aid in theassessment of breast cancerpatients for whom HERCEPTIN®(Trastuzumab) treatment is beingconsidered. Note: The actualcorrelation of the DakoHercepTest™ to Herceptin®clinical outcome has not beenestablished. | HER-2/neu receptor protein. Thepathologist should verify agreementwith the Image Analysis softwareapplication score. The accuracy of thetest results depends on the quality of theimmunohistochemical staining. It is theresponsibility of a qualified pathologistto employ appropriate morphologicalstudies and controls as specified in theinstructions for the PATHWAY® anti-HER-2.neu (4B5) Rabbit MonoclonalPrimary Antibody assay used to assurethe validity of the iScan System for IHCHER2 Digital Read and Image Analysisscores. The actual correlation ofPATHWAY® anti-HER-2/neu (4B5) toclinical outcome has not beenestablished. | ||
| Specimen Type | Formalin-fixed, paraffin-embedded normal andneoplastic tissueimmunohistochemically stained | Same | Same |
| DeviceComponents | Automated digital slide scanner,computer, color monitor,keyboard, and digital pathologyinformation managementsoftware | Automated digital microscopeslide scanner, computer, colormonitor, keyboard and digitalpathology informationmanagement software | BioImagene (now Ventana) iScan slidescanner, computer, color monitor,proprietary software for HER2 (4B5) |
| ImageAcquisition | Tile sensor technology | Line scanning technology | Same |
| Light Source | LED | Tungsten light | Same |
| PrimaryAntibody(Assay)Reagent | Dako Reagents for HER2(HercepTest™) | Same | Ventana PATHWAY HER2 (4B5)(P990081 S003) |
| Interpretation (Modes ofOperation) | Interpretation is performed bythe pathologist ( Manual digitalread) | Same | Manual and Automated |
Similarities/Differences of Omnyx Manual Read of the Digital HER2 Application with Predicate Devices
Omnyx, LLC Traditional 510(k) K131140 Manual Read of the Digital HER2 Application on the Omnyx IDP System
{4}------------------------------------------------
.
,
i
{5}------------------------------------------------
- SUMMARY OF NON-CLINICAL AND CLINICAL PERFORMANCE TESTING AS BASIS FOR SUBSTANTIAL EQUIVALENCE
CLINICAL COMPARISON TO MANUAL MICROSCOPY
Each of the four (4) pathologists read 200 breast cancer cases, comprising of both the controls and specimen slides stained with the Dako HercepTest™, using a conventional manual microscope (MM) and the Omnyx™ IDP (M-WSI), separated by at least a 2 week washout period. Three (3) VL4 scanners were installed in separate laboratories, with each scanner associated with a different scanner technician. Each pathologist reviewed WSIs obtained from different VL4 scanners, although two (2) of the pathologists received WSIs from the same VL4 scanner. The pairwise percent agreement between all pathologist on both MM and M-WSI modalities (inter-reader/intra-modality) was determined for both binned (0/1+ = neg; 1+/2+ = pos) and trichotomous (0/1+, 2+, 3+) score categories. Furthermore, in order to determine how well each pathologist could recapitulate a slide score for each slide when read on each modality, an analysis of the percent agreement between MM vs. M-WSI (inter-modality/intra-reader) for each pathologist was determined.
| Inter-Reader/Intra-Modality(MM) | Pathologist 2 | Pathologist 3 | Pathologist 4 | Pathologist 3 | Pathologist 4 | Pathologist 4 | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | 0+ | 1+ | 2+ | 3+ | ||
| Pathologist 1 | 0+ | 46 | 9 | 1 | 0 | 50 | 6 | 0 | 0 | 46 | 9 | 0 | 0 | ||||||||||||
| 1+ | 7 | 18 | 8 | 1 | 7 | 22 | 6 | 0 | 1 | 30 | 3 | 0 | |||||||||||||
| 2+ | 0 | 7 | 28 | 4 | 1 | 6 | 32 | 0 | 0 | 23 | 15 | 0 | |||||||||||||
| 3+ | 1 | 0 | 6 | 63 | 0 | 0 | 11 | 59 | 0 | 0 | 12 | 56 | |||||||||||||
| Pathologist 2 | 0 | 50 | 3 | 1 | 0 | 43 | 9 | 1 | 0 | ||||||||||||||||
| 1+ | 7 | 23 | 4 | 0 | 3 | 30 | 2 | 0 | |||||||||||||||||
| 2+ | 1 | 7 | 34 | 1 | 1 | 22 | 19 | 0 | |||||||||||||||||
| 3+ | 0 | 0 | 10 | 58 | 0 | 1 | 8 | 56 | |||||||||||||||||
| Pathologist 3 | 0 | 46 | 11 | 0 | 0 | ||||||||||||||||||||
| 1+ | 1 | 32 | 1 | 0 | |||||||||||||||||||||
| 2+ | 0 | 19 | 26 | 2 | |||||||||||||||||||||
| 3+ | 0 | 0 | 3 | 54 | |||||||||||||||||||||
| % Agreement (95% CI)(Trichotomous) | 85.9% (80%-90%) | 88.0% (83%-92%) | 80.5% (74%-85%) | 87.9% (83%-92%) | 82.1% (76%-87%) | 87.2% (82%-91%) |
Inter-Reader/Intra-Modality on Glass (MM) between four (4) pathologists - Trichotomous score categories
{6}------------------------------------------------
| Inter-Reader/Intra-Modality | Pathologist 2 | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (M-WSI) | 04 | 1+ | 2+ | 34 | 04 | 14 | 2+ | 34 | 0+ | 14 | 24 | 3+ | 0+ | 1+ | 24 | ਤੇ + | 04 | 1+ | 24 | 34 | 04 | 1+ | 2+ | 34 | |
| 0 | 48 | હ | O | 0 | 28 | 21 | ટ | 0 | 29 | 22 | 0 | 0 | |||||||||||||
| 1+ | শ | 22 | 11 | 1 | 1 | 11 | 23 | 3 | 0 | તે વ | ਤੇ | 0 | |||||||||||||
| Pathologist 1 | 24 | 0 | 7 | 26 | ર | ਹੈ | 0 | Pathologist 4Pathologist 3Pathologist 4Pathologist 4Pathologist 32016।191912રવ୧୧ﻠ702102820128ﻠﺴﺎর্ব1212201ਤੇ ਤੋ000022। ਰੇ202220364ತಿടટે પે00025ന002600414080718164.4% (57%-71%)73.4% (67%-79%)82.4% (76%-87%)74.4% (68%-80%)83.5% (78%-88%) | |||||||||||||||||
| 34 | 1 | 0 | 7 | દર્ભ | 0 | 0 | |||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| Pathologist 2 | 1+ | ||||||||||||||||||||||||
| 2+ | |||||||||||||||||||||||||
| 34 | |||||||||||||||||||||||||
| 0 | |||||||||||||||||||||||||
| 1+ | |||||||||||||||||||||||||
| Pathologist 3 | 2+ | ||||||||||||||||||||||||
| 3+ | ટર્ટ | ||||||||||||||||||||||||
| % Agreement (95% Cl)(Trichotomous) | 83.4% (78%-88%) |
Inter-Reader/Intra-Modality on Digital (M-WSI) between four (4) pathologists – Trichotomous score categories
To calculate the negative & positive percent agreements, the 4x4 binary agreements are binned into a 2x2 table with 0/1+ (Negative) combined and 2+/3+ (Positive) combined. Since neither pathologist can be considered a reference in each pairwise reader comparison, analysis for negative and positive score categories is provided as Average Negative Agreement (ANA) and Average Positive Agreement (APA).
| Inter-Reader/Intra-Modality(MM) | Pathologist 2 | Pathologist 3 | Pathologist 4 | Pathologist 3 | Pathologist 4 | Pathologist 4 | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | |||
| Pathologist 1 | Neg | 80 | 10 | 85 | 6 | 86 | 3 | |||||||
| Pos | 8 | 101 | 7 | 102 | 23 | 83 | ||||||||
| Pathologist 2 | Neg | 83 | 5 | 85 | 3 | |||||||||
| Pos | 8 | 103 | 24 | 83 | ||||||||||
| Pathologist 3 | Neg | 90 | 1 | |||||||||||
| Pos | 19 | 85 | ||||||||||||
| Overall PercentAgreement(95% CI) | 91.0%(86%-94%) | 93.5%(89%-96%) | 86.7%(81%-91%) | 93.5%(89%-96%) | 86.2%(81%-90%) | 89.7%(85%-93%) | ||||||||
| Average PositiveAgreement(95% CI) | 89.9%(85%-94%) | 92.9%(88%-96%) | 86.9%(81%-91%) | 92.7%(88%-96%) | 86.3%(81%-90%) | 90.0%(85%-93%) | ||||||||
| Average NegativeAgreement(95% CI) | 91.8%(87%-95%) | 94.0%(90%-96%) | 86.5%(81%-91%) | 94.1%(90%-96%) | 86.0%(80%-90%) | 89.5%(84%-93%) |
Inter-Reader/Intra-Modality on Glass (MM) between four (4) pathologists - Binary score categories
{7}------------------------------------------------
| Inter-Reader/Intra-Modality(M-WSI) | Pathologist 2 | Pathologist 3 | Pathologist 4 | Pathologist 3 | Pathologist 4 | Pathologist 4 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | |
| Pathologist 1 | 80 | 12 | 61 | 31 | 85 | 3 | ||||||
| Pathologist 1 | 8 | 99 | 1 | 106 | 22 | 78 | ||||||
| Pathologist 2 | 62 | 26 | 83 | 1 | ||||||||
| Pathologist 2 | 0 | 111 | 24 | 80 | ||||||||
| Pathologist 3 | 58 | 0 | ||||||||||
| Pathologist 3 | 49 | 81 | ||||||||||
| Overall PercentAgreement(95% CI) | 89.9%(85%-93%) | 83.9%(78%-88%) | 86.7%(81%-91%) | 86.9%(82%-91%) | 86.7%(81%-91%) | 73.9%(67%-80%) | ||||||
| Average PositiveAgreement(95% CI) | 88.9%(83%-93%) | 79.2%(72%-85%) | 87.2%(82%-91%) | 82.7%(76%-88%) | 86.9%(81%-91%) | 70.3%(63%-77%) | ||||||
| Average NegativeAgreement(95% Cl) | 90.8%(86%-94%) | 86.9%(82%-91%) | 86.2%(80%-90%) | 89.5%(85%-93%) | 86.5%(81%-91%) | 76.8%(71%-82%) |
Inter-Reader/Intra-Modality on Digital (M-WSI) between four (4) pathologists - Binary score categories
The inter-modality/intra-reader agreement results evaluating glass vs. digital (MM vs. M-WSI) for all four (4) pathologists are shown below. The washout period between the glass and digital reads was a minimum of 2 weeks.
| Inter-Modality/Intra-Reader(MM vs. M-WSI) | Glass (MM) | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Digital (M-WSI) | Pathologist 1 | Pathologist 2 | Pathologist 3 | Pathologist 4 | ||||||||||||
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | |
| 0 | 50 | 4 | 0 | 0 | 47 | 3 | 2 | 1 | 29 | 1 | 0 | 0 | 29 | 0 | 2 | 0 |
| 1+ | 6 | 26 | 6 | 0 | 5 | 25 | 5 | 0 | 25 | 7 | 0 | 0 | 16 | 54 | 5 | 0 |
| 2+ | 0 | 5 | 32 | 2 | 0 | 7 | 30 | 7 | 4 | 24 | 21 | 0 | 0 | 6 | 20 | 0 |
| 3+ | 0 | 0 | 1 | 67 | 2 | 0 | 6 | 60 | 0 | 2 | 28 | 58 | 0 | 0 | 3 | 5 |
Intra-Reader/Inter-Modality comparing agreement between glass and digital (MM vs. M- WSI) for each of the four (4) pathologists . Trichotomous score categories
To calculate the negative & positive percent agreements, the 4x4 binary agreement tables are binned into a 2x2 table with 0/1+ (Negative) combined and 2+/3+ (Positive) combined. Since the glass scores for each pathologist is used as their respective reference, the analysis is provided as Negative Percent Agreement (NPA) and Positive Percent Agreement (PPA), with the glass reads as the imperfect reference.
{8}------------------------------------------------
| Glass (MM) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Inter-Modality/Intra-Reader(MM vs. M-WSI) | Pathologist 1 | Pathologist 2 | Pathologist 3 | Pathologist 4 | ||||
| Neg | Pos | Neg | Pos | Neg | Pos | Neg | Pos | |
| Digital (M-WSI)Neg | 86 | 8 | 80 | 8 | 62 | 0 | 99 | 7 |
| Digital (M-WSI)Pos | 5 | 75 | 9 | 103 | 30 | 107 | 6 | 75 |
| Overall Percent Agreement(95% CI) | 92.5%(88%-96%) | 91.5%(87%-95%) | 89.4%(79%-89%) | 93.0%(88%-96%) | ||||
| Negative Percent Agreement(95% CI) | 94.5%(88%-98%) | 89.9%(82%-95%) | 67.4%(57%-76%) | 94.3%(88%-97%) | ||||
| Positive Percent Agreement(95% CI) | 90.4%(82%-95%) | 92.8%(86%-96%) | 100%(97%-100%) | 91.5%(83%-96%) |
Intra-Reader/Inter-Modality comparing agreement between glass and digital (MM vs. M- WSI) for each of the four (4) pathologists - Binary score categories
The pairwise inter-reader/intra-modality percent agreements do not differ significantly between MM and M-WSI. Additionally, there are high percent agreements between MM and M-WSI for each pathologist when examined by binary or trichotomous score category.
PRECISION & REPRODUCIBILITY
INTRA-READER/INTER-DAY
In order to compare the intra-reader variability on digital M-WSI, three (3) pathologist performed three (3) independent readings of a set of the HercepTest™ stained slides (n=40) using the M-WSI modality. Each of the three reads was separated by a minimum one week wash out, with the inclusion of wildcards. The results are presented as both trichotomous and binary analysis, with additional negative and positive percent agreements (NPA and PPA).
| Intra-Reader/Inter-Day(M-WSI) | Read 2 | Read 3 | Read 3 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | ||
| Read 1 | 0 | 6 | 3 | 1 | 0 | 8 | 2 | 0 | 0 | ||||
| 1+ | 0 | 3 | 11 | 0 | 0 | 8 | 6 | 0 | |||||
| 2+ | 0 | 0 | 4 | 3 | 0 | 0 | 4 | 3 | |||||
| 3+ | 0 | 0 | 0 | 9 | 0 | 0 | 0 | 9 | |||||
| Read 2 | 0 | 6 | 0 | 0 | 0 | ||||||||
| 1+ | 2 | 4 | 0 | 0 | |||||||||
| 2+ | 0 | 6 | 10 | 0 | |||||||||
| 3+ | 0 | 0 | 0 | 12 | |||||||||
| % Agreement (95% CI)(Trichotomous) | 62.5% (47%-76%) | 77.5% (62%-88%) | 85.0% (71%-93%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 1 – Trichotomous score categories
{9}------------------------------------------------
| Intra-Reader/Inter-Day(M-WSI)Pathologist 1 | Read 2 | Read 3 | Read 3 | ||||
|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Read 1 | Neg | 12 | 12 | 18 | 6 | ||
| Pos | 0 | 16 | 0 | 16 | |||
| Read 2 | Neg | 12 | 0 | ||||
| Pos | 6 | 22 | |||||
| Overall % Agreement(95% CI) | 70.0% (55%-82%) | 85.0% (71%-93%) | 85.0% (71%-93%) | ||||
| Negative % Agreement(95% CI) | 66.7% (50%-80%) | 85.7% (72%-93%) | 80.0% (63%-90%) | ||||
| Positive % Agreement(95% CI) | 72.7% (58%-84%) | 84.2% (70%-93%) | 88.0% (76%-94%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 1 - Binary score categories
| Intra-Reader/Inter-Day(M-WSI) | Read 2 | Read 3 | Read 3 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | ||||
| Read 1 | 0 | 8 | 0 | 0 | 0 | 8 | 0 | 0 | 0 | ||||||
| 1+ | 0 | 8 | 1 | 0 | 1 | 8 | 0 | 0 | |||||||
| 2+ | 0 | 1 | 10 | 0 | 0 | 1 | 10 | 0 | |||||||
| 3+ | 0 | 0 | 0 | 12 | 0 | 0 | 0 | 12 | |||||||
| Read 2 | 1 | 8 | 0 | 0 | 0 | ||||||||||
| 1+ | 1 | 8 | 0 | 0 | |||||||||||
| 2+ | 0 | 1 | 10 | 0 | |||||||||||
| 3+ | 0 | 0 | 0 | 12 | |||||||||||
| % Agreement (95% CI)(Trichotomous) | 95.0% (83%-99%) | 97.5% (87%-100%) | 97.5% (87%-100%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 2 - Trichotomous score categories
| Intra-Reader/Inter-Day(M-WSI)Pathologist 2 | Read 2 | Read 3 | Read 3 | ||||
|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Read 1 | Neg | 16 | 1 | 17 | 0 | ||
| Read 1 | Pos | 1 | 22 | 1 | 22 | ||
| Read 2 | Neg | 17 | 0 | ||||
| Pos | 1 | 22 | |||||
| Overall % Agreement(95% CI) | 95.0% (83%-99%) | 97.5% (87%-100%) | 97.5% (87%-100%) | ||||
| Negative % Agreement(95% CI) | 94.1% (81%-98%) | 97.1% (85%-99%) | 97.1% (85%-99%) | ||||
| Positive % Agreement(95% CI) | 95.7% (85%-99%) | 97.8% (88%-100%) | 97.8% (88%-100%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 2 - Binary score categories
{10}------------------------------------------------
| Intra-Reader/Inter-Day(M-WSI) | Read 2 | Read 3 | Read 3 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | ||
| Read 1 | 0 | 5 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | ||||
| 1+ | 3 | 3 | 0 | 0 | 1 | 5 | 0 | 0 | |||||
| 2+ | 0 | 1 | 15 | 3 | 0 | 0 | 15 | 4 | |||||
| 3+ | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 10 | |||||
| Read 2 | 1 | 5 | 3 | 0 | 0 | ||||||||
| 1+ | 1 | 2 | 1 | 0 | |||||||||
| 2+ | 0 | 0 | 14 | 1 | |||||||||
| 3+ | 0 | 0 | 0 | 13 | |||||||||
| % Agreement (95% CI)(Trichotomous) | 90.0% (77%-96%) | 90.0% (77%-96%) | 95.0% (83%-99%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 3 - Trichotomous score categories
| Intra-Reader/Inter-Day(M-WSI)Pathologist 3 | Read 2 | Read 3 | Read 3 | ||||
|---|---|---|---|---|---|---|---|
| Neg | Pos | Neg | Pos | Neg | Pos | ||
| Read 1 | Neg | 11 | 0 | 11 | 0 | ||
| Pos | 1 | 28 | 0 | 29 | |||
| Read 2 | Neg | 11 | 1 | ||||
| Pos | 0 | 28 | |||||
| Overall % Agreement(95% CI) | 97.5% (87%-100%) | 100.0% (91%-100%) | 97.5% (87%-100%) | ||||
| Negative % Agreement(95% CI) | 95.7% (79%-99%) | 100.0% (85%-100%) | 95.7% (79%-99%) | ||||
| Positive % Agreement(95% CI) | 98.2% (91%-100%) | 100.0% (94%-100%) | 98.2% (91%-100%) |
Intra-Reader/Inter-Day on Digital (MM) for Pathologist 3 - Binary score categories
.
{11}------------------------------------------------
INTER-SCANNER/INTRA-READER
To determine the scanner variability, we performed a subjective inter-scanner study. A set of 80 regions of interest (ROIs) extracted from WSIs of forty (40) HercepTest™ slides, with even distribution of the score categories, were obtained from three (3) different scanners. The three scanners were located in three different laboratory locations within GE Healthcare and operated by three independent operators. Each read session (for each scanner) was separated by a minimum of 1 week washout period, with the inclusion of wildcard ROIs during each scanner's ROI reads. All ROIs were manually scored by a single pathologist based on the Dako HercepTest™ scoring guidelines. Percent agreement between each of the scanner pairs were determined based on the ROI scores.
| Inter-Scanner/Intra-Reader | Scanner 2 | Scanner 3 | Scanner 3 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | 0 | 1+ | 2+ | 3+ | ||
| Scanner 1 | 0 | 25 | 2 | 0 | 0 | 26 | 1 | 0 | 0 | ||||
| 1+ | 3 | 11 | 1 | 0 | 3 | 10 | 2 | 0 | |||||
| 2+ | 0 | 0 | 19 | 3 | 0 | 1 | 15 | 6 | |||||
| 3+ | 0 | 0 | 0 | 16 | 0 | 0 | 0 | 16 | |||||
| Scanner 2 | 0 | 26 | 2 | 0 | 0 | ||||||||
| 1+ | 3 | 9 | 1 | 0 | |||||||||
| 2+ | 0 | 1 | 15 | 4 | |||||||||
| 3+ | 0 | 0 | 1 | 18 | |||||||||
| % Agreement (95% CI)(Trichotomous) | 95.0% (88%-98%) | 88.8% (80%-94%) | 91.3% (83%-96%) |
Inter-Scanner/Intra-Reader Agreement using Region of Interests (ROIs) obtained from 3 VL4 scanners and scored by a single pathologist 2) - Trichotomous score categories
When analyzed trichotomously (0/1+, 2+ and 3+), the inter-scanner/intra-reader variability had high percent agreement across all pairwise scanner comparisons. This data indicates a very high reproducibility among scanners and further suggests that M-WSI inter-scanner variability is primarily due to the subjectivity of score interpretation of the readers and not by scanner to scanner variability.
{12}------------------------------------------------
9. SUMMARY OF OTHER INFORMATION
This submission included a comparison of intended use statements, proposed product labeling, software validation and summary information and labeling on predicate devices.
10. CONCLUSIONS DRAWN FROM NON-CLINICAL AND CLINICAL TESTS
Based on the information provided in this 510(k), Omnyx believes that the proposed Omnyx Manual Read of the Digital HER2 Application is substantially equivalent to the previously cleared products. The proposed device raises no new issues of safety and effectiveness. The non-clinical and clinical testing performed demonstrates that the proposed device met all the specifications and is suitable for its intended use.
{13}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/13/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird-like figure.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
April 1, 2014
Omnyx, LLC. c/o Gail E. Radcliffe. Ph.D. Aptiv Solutions 62 Forest Street, Suite 300 Marlborough, MA 01752
Re: K131140
Trade/Device Name: OmnyxManual Read of the Digital HER2 Application Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: II Product Code: OEO Dated: March 12, 2014 Received: March 13, 2014
Dear Dr. Radcliffe:
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 that I DA has made a actoring administered by other Federal agencies. You must Of any I edical statutes and registments, including, but not limited to: registration and listing (21 comply with an the For 3 requirements, more of 800 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements medical device-related adverse overles (22) regulation (21 CFR Part 820); and if applicable, the as set form in the quality of ovisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
{14}------------------------------------------------
Page 2- Gail E. Radcliffe
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours.
ReenauPhilip-S
for
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
{15}------------------------------------------------
Indications for Use
510(k) Number (if known) K131140
Device Name
Omnyx Manual Read of the Digital HER2 Application
Indications for Use (Describe)
The Omnyx Manual Read of the Digital HER2 Application on the Ominyx IDP System is intended for in vitro diagnostic use as an aid to pathology professionals for creating, storing, annotating, measuring, and viewing digital Whole Shide Images (WS1) from formalin-fixed, parafin-embedded (FFPE) tissue sections stained with the Dako HercepTest™
The Omnyx Manual Read of the Digital HER2 Application on the Omnyx IDP System is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of HER2/neu (c-erbB-2) in digital images of FFPE breast cancer tissue immunohistochemically stained with the Dako HercepTest™ and viewed on a computer monitor.
The Dako HercepTest™ is indicated for use as an aid in the assessment of breast cancer patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Image /page/15/Picture/16 description: The image shows the text "Yun-fDHu-S" in a bold, sans-serif font. The letters "Yun" and "S" are clearly visible and easily readable. The letters between "Yun" and "S" are stylized with decorative patterns, making them less distinct but still recognizable as "fDHu".
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the The burden instructions, search existing data sources, gather and mainlain the data needed and complete lifre to review instructions, search calling data obtrool, games in this burden estimate or any other aspect and rowled the collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
§ 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.