Contains Nonbinding Recommendations 
 
Technical Performance Assessment 
of Digital Pathology Whole Slide 
Imaging Devices 
Guidance for Industry and Food 
and Drug Administration Staff 
Document issued on: April 20, 2016 
The draft of this document was issued on February 25, 2015 
For questions about this document, contact the Division of Molecular Genetics and 
Pathology at 301-796-6179 and Nicholas Anderson at 301-796-4310 or 
nicholas.anderson@fda.hhs.gov or Aldo Badano at 301-796-2534 or 
aldo.badano@fda.hhs.gov. 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
 
Office of In Vitro Diagnostics and Radiological Health 
Division of Molecular Genetics and Pathology 
Molecular Pathology and Cytology Branch 
 
  Contains Nonbinding Recommendations 
Preface 
Public Comment 
You may submit electronic comments and suggestions at any time for Agency 
consideration to http://www.regulations.gov . Submit written comments to the Division of 
Dockets Management, Food and Drug Administration, 5630 Fishers Lane, Room 1061, 
(HFA-305), Rockville, MD 20852. Identify all comments with the docket number [FDA-
2015-D-0230]. Comments may not be acted upon by the Agency until the document is next 
revised or updated. 
Additional Copies 
Additional copies are available from the Internet.  You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance.  Please use the document 
number 1400053 to identify the guidance you are requesting. 
  Contains Nonbinding Recommendations 
Table of Contents 
I.  Introduction...............................................................................................................1
II.  Background...............................................................................................................2
III.  Scope.........................................................................................................................2
IV.  Policy .........................................................................................................................3
IV(A).  Description and Test Methods for Each Component ....................................3
IV(A)(1).  Slide Feeder...........................................................................................5
IV(A)(1)(a).  Description ....................................................................................5
IV(A)(2).  Light Source..........................................................................................5
IV(A)(2)(a).  Description ....................................................................................5
IV(A)(2)(b).  Test Method..................................................................................6
IV(A)(3).  Imaging Optics......................................................................................6
IV(A)(3)(a).  Description ....................................................................................6
IV(A)(3)(b).  Test Methods................................................................................7
IV(A)(4).  Mechanical Scanner Movement............................................................7
IV(A)(4)(a).  Description ....................................................................................7
IV(A)(4)(b).  Test Method..................................................................................8
IV(A)(5).  Digital Imaging Sensor ..........................................................................8
IV(A)(5)(a).  Description ....................................................................................8
IV(A)(5)(b).  Test Methods................................................................................8
IV(A)(6).  Image Processing Software...................................................................9
IV(A)(6)(a).  Description ....................................................................................9
IV(A)(6)(b).  Resources ......................................................................................9
IV(A)(7).  Image Composition...............................................................................9
IV(A)(7)(a).  Description ....................................................................................9
IV(A)(7)(b).  Test Methods .............................................................................. 10
IV(A)(8).  Image Files Formats ............................................................................ 10
IV(A)(8)(a).  Description .................................................................................. 10
IV(A)(9).  Image Review Manipulation Software ................................................ 11
IV(A)(9)(a).  Description .................................................................................. 11
IV(A)(9)(b).  Resources .................................................................................... 11
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IV(A)(10).  Computer Environment ...................................................................... 11
IV(A)(10)(a).  Description ................................................................................ 11
IV(A)(11).  Display ............................................................................................... 12
IV(A)(11)(a).  Description ................................................................................ 12
IV(A)(11)(b).  Test Methods ............................................................................ 12
IV(A)(11)(c).  Resources .................................................................................. 13
IV(B).  System-level Assessment ............................................................................ 14
IV(B)(1).  Color Reproducibility .......................................................................... 15
IV(B)(1)(a).  Description .................................................................................. 15
IV(B)(1)(b).  Test Methods ............................................................................... 15
IV(B)(1)(c).  Resources .................................................................................... 16
IV(B)(2).  Spatial Resolution ................................................................................ 16
IV(B)(2)(a).  Description .................................................................................. 16
IV(B)(2)(b).  Test Methods ............................................................................... 16
IV(B)(3).  Focusing Test ....................................................................................... 16
IV(B)(4).  Whole Slide Tissue Coverage.............................................................. 17
IV(B)(4)(a).  Description .................................................................................. 17
IV(B)(4)(b).  Test Method ................................................................................ 17
IV(B)(5).  Stitching Error ..................................................................................... 18
IV(B)(5)(a).  Description .................................................................................. 18
IV(B)(5)(b).  Test Methods ............................................................................... 18
IV(B)(6).  Turnaround Time ................................................................................. 19
IV(B)(6)(a).  Description .................................................................................. 19
IV(C).  User Interface .............................................................................................. 19
IV(C)(1).  Description........................................................................................... 19
IV(C)(2).  Test Methods ....................................................................................... 19
IV(C)(3).  Resources ............................................................................................. 22
IV(D).  Labeling ...................................................................................................... 22
IV(D)(1).  Test Methods ....................................................................................... 23
IV(D)(2).  Resources ............................................................................................. 23
IV(E).  Quality Control ........................................................................................... 23
   
Technical Performance Assessment 
1
of Digital Pathology Whole Slide 
2
Imaging Devices 
3
4
Guidance for Industry and Food 
5
and Drug Administration Staff 
6
7
8 This guidance represents the current thinking of the Food and Drug Administration 
9 (FDA or Agency) on this topic.  It does not establish any rights for any person and is 
10 not binding on FDA or the public.  You can use an alternative approach if it satisfies 
11 the requirements of the applicable statutes and regulations.  To discuss an alternative 
12 approach, contact the FDA staff or Office responsible for this guidance as listed on the 
13 title page.  
14
I.  Introduction  
15
16
17 FDA is issuing this guidance to provide industry and agency staff with recommendations 
18 regarding the technical performance assessment data that should be provided for 
19 regulatory evaluation of a digital whole slide imaging (WSI) system.  This document 
20 does not cover the clinical submission data that may be necessary to support approval or 
21 clearance.  This document provides our suggestions on how to best characterize the 
22 technical aspects that are relevant to WSI performance for their intended use and 
23 determine any possible limitations that might affect their safety and effectiveness.   
24
25 Recent technological advances in digital microscopy, in particular the development of 
26 whole slide scanning systems, have accelerated the adoption of digital imaging in 
27 pathology, similar to the digital transformation that radiology departments have 
28 experienced over the last decade.  FDA regulates WSI system manufacturers to help 
29 ensure that the images intended for clinical uses are reasonably safe and effective for 
30 such purposes.  Essential to the regulation of these systems is the understanding of the 
31 technical performance of the WSI system and the components in the imaging chain, from 
32 image acquisition to image display and their effect on pathologists diagnostic 
33 performance and workflow.  Prior to performing non-technical analytical studies (i.e., 
34 those using clinical samples) and clinical studies to evaluate a digital imaging systems 
35 performance, the manufacturer should first determine the technical characteristics that are 
36 relevant to such performance for its intended use and determine any possible limitations 
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37 that might affect its safety and effectiveness.  This guidance provides recommendations 
38 for the assessment of technical characteristics of a WSI device. 
39
40 FDA's guidance documents, including this guidance, do not establish legally enforceable 
41 responsibilities.  Instead, guidances describe the Agency's current thinking on a topic and 
42 should be viewed only as recommendations, unless specific regulatory or statutory 
43 requirements are cited.  The use of the word should in Agency guidance means that 
44 something is suggested or recommended, but not required.  
45
II.  Background 
46
47
48 For over a hundred years, the reference method for the diagnosis of cancer and many 
49 other critical clinical conditions has been histopathological examination of tissues using 
50 conventional light microscopy.  This process is known as surgical pathology in the 
51 United States. 
52
53 In surgical pathology, patient tissue from surgery, biopsy or autopsy goes through a 
54 process that includes dissection, fixation, embedding, and cutting of tissue into very thin 
55 slices which are then stained, for example by the hematoxylin and eosin (H&E) protocol, 
56 and permanently mounted onto glass slides.  The slides are examined by a pathologist 
57 under a light microscope by dynamically adjusting the focus and using different 
58 magnifications.  By integrating their interpretations obtained by microscopic examination 
59 of the tissue from all slides pertaining to a case, pathologists arrive at a diagnosis of the 
60 case.  
61
62 WSI refers to the digitization of the stained entire tissue specimen on a glass slide.  The 
63 glass slide is still prepared and stained just as for conventional light microscopy.  
64 Depending on the system used, various magnifications, scanning methodologies, 
65 hardware, and software are employed to convert the optical image of the slide into a 
66 digital whole slide image.  With WSI, the pathologist views the image on a computer 
67 monitor rather than through the microscope oculars.   
68
III.  Scope 
69
70
71 This document provides guidance regarding only the technical performance assessment 
72 of WSI systems for regulatory evaluation.  WSI systems are defined here as those 
73 consisting of (a) an image acquisition subsystem that converts the content of a glass slide 
74 into a digital image file, and (b) a workstation environment for viewing the digital 
75 images.  If not otherwise specified, the term image in the context of whole slide 
76 imaging refers to a pyramid structure consisting of multiple images at different 
77 resolutions. The baseline image has the highest resolution.  This guidance is applicable 
78 for surgical pathology tasks performed in the anatomic pathology laboratory.  It is 
79 intended to provide recommendations to industry and FDA staff regarding only the 
80 technical performance assessment data needed for the regulatory evaluation of a WSI 
81 device.  This document is not meant to provide guidance for special stain techniques or 
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82 fluorescence imaging or for the non-technical analytical studies (utilizing clinical 
83 samples) or pivotal clinical studies necessary to support safety and effectiveness, nor 
84 does this guidance alone suffice to demonstrate safety and effectiveness of WSI systems.  
85 Interpretation of WSI images on mobile platforms is beyond the scope of this guidance.  
86
IV.  Policy 
87
88
89 The following subsections of this section describe the technical performance assessment 
90 data FDA believes will facilitate the regulatory evaluation of a WSI device.    
91
IV(A).  Description and Test Methods for Each Component 
92
93
94 This subsection details the descriptions and the test methods at the component level that 
95 should be included in the technical performance assessment of a WSI device.  For 
96 purposes of this guidance only, a component is a piece of hardware, software, or a 
97 combination of hardware and software that processes the image signals flowing through 
98 the imaging chain.  The concept of a component is based on the transformation of the 
99 image signals.  For example, the digital imaging sensor is a hardware device that converts 
100 optical signals into digital signals.  The image composition component is a software 
101 program that stitches sub-images together to form a whole slide image.  A component 
102 and a physical device need not be in close physical proximity.  For example, the light 
103 source component and the image optics component are usually tightly coupled within the 
104 same device, while the display calibration data is often distributed in both the color 
105 profile in the computer environment component and the on-screen display settings in the 
106 display component. 
107
108 The components in a WSI device can be grouped in two subsystems: image acquisition 
109 and image display.  The image acquisition subsystem digitizes the tissue slide as a digital 
110 image file.  The image display subsystem converts the digital image file into optical 
111 signals for the human reader.  In the paradigm of telemedicine, the digital image file can 
112 be electronically sent to a remote site for reading, so the image acquisition subsystem and 
113 the image display subsystem do not need to be physically coupled.  Methods for 
114 independently testing the image acquisition and display subsystems are described in 
115 Section IV(B). 
116
117 Sponsors should provide a block diagram of the components found in the WSI system in 
118 the premarket submission.  A chart indicating the relationship among the components and 
119 the test methods utilized for the specific system characterization should also be provided.  
120 Diagram 1 on the following page is offered as an example block diagram of typical 
121 components found in current WSI systems.  The components of a particular WSI system 
122 might not include all of those listed in the diagram or may include additional 
123 components.  Sponsors are encouraged to provide additional diagrams, illustrations, and 
124 photographs of their devices as part of their submissions. 
125
126
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127 Diagram 1: Example block diagram of typical components found in current WSI 
128 systems 
129
130  
131  
132  
133  
134  
135  
136  
137  
138  
139  
140  
141  
142  
143  
144  
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148  
149  
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158  
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167
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168 IV(A)(1).  Slide Feeder 
169
170 IV(A)(1)(a).  Description 
171
172 The slide feeder is the mechanism(s) used to introduce the slide(s) to the scanner.  For the 
173 slide feeder, sponsors should provide the following information, if applicable: 
174   Configuration of the slide feed mechanism (a physical description of the 
175 equipment) 
176 o  Slide configuration (physical description of the slide (i.e., custom or 
177 commercial off-the-shelf)) 
178 o  Number of slides in queue (carrier) 
179 o  Class of automation (e.g., robotics, pneumatics, etc.) 
180   User interaction 
181 o  Hardware (e.g., loading of slides into carrier) 
182 o  Software (e.g., does the system recognize the number of slides or is this 
183 specified by the user) 
184 o  Feedback (e.g., alarms, notifications, etc.) 
185 o  Failure Mode and Effects Analysis (FMEA) (including severity, 
186 likelihood, mitigations, etc.) 
187
188 IV(A)(2).   Light Source 
189
190 IV(A)(2)(a).  Description 
191
192 The light source, including the light guide, generates and delivers light to the slide being 
193 imaged.  The two major components are the lamp and condenser.  For the light source, 
194 sponsors should provide the following information and specifications, if applicable: 
195   Lamp 
196 o  Bulb type (e.g., halogen, xenon arc, LED) 
197 o  Manufacturer and model 
198 o  Wattage 
199 o  Spectral power distribution 
200 o  Expected lifetime 
201 o  Output adjustment control (electrical/electronic/mechanical)
202 o  Optical filter(s) 
203   Type (e.g., heat blocking, polarization, neutral density, diffusing) 
204 o  Manufacturer and model 
205 o  Expected intensity variation (coefficient of variation ) 
206   Over the duration of scanning a single slide 
207   Over the course of a single workday 
208   Over the lifetime of the device 
209 o  Expected spectral variation 
210   Over the duration of scanning a single slide 
211   Over the course of a single workday 
212   Over the lifetime of the device 
213 o  Capability of tracking intensity and spectral degradation with lifetime 
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214   Condenser 
215 o  Illumination format (e.g., Kohler, critical) 
216 o  Manufacturer and model 
217 o  Numerical aperture 
218 o  Focal length 
219 o  Working distance 
220
221 IV(A)(2)(b).  Test Method 
222
223 The following steps should be used to measure the spectral distribution of light incident 
224 on the slide.  Position the input of a calibrated spectrometer or monochromator at the 
225 plane where the slide would be placed, centered on the illumination spot from the 
226 condenser.  If desired, the light can be coupled into the spectrometer via light guide (e.g., 
227 fiber optic cable) or an integrating sphere.  The measurement aperture should be at least 
228 as large as the anticipated field of view on the slide at the lowest magnification of the 
229 imaging optics.  The wavelength accuracy and relative spectral efficiency of the 
230 spectrometer or monochromator in the wavelength range of 360-830 nm should be 
231 calibrated prior to measurements and reported.  Plots of the measured spectrum with at 
232 least 10 nm spectral resolution should be provided, using radiometric units (e.g., spectral 
233 irradiance in W/cm2/nm, spectral radiance in W/sr/cm2/nm). 
234
235 IV(A)(3).  Imaging Optics 
236
237 IV(A)(3)(a).  Description 
238
239 The imaging optics comprises the microscope objective and auxiliary lens(es) (e.g., tube 
240 lens), which optically transmit an image of the tissue from the slide to the digital image 
241 sensor.  Sponsors should provide the following information and specifications, if 
242 applicable: 
243   Optical schematic with all optical elements identified from slide (object plane) to 
244 digital image sensor (image plane) 
245   Microscope objective 
246 o  Manufacturer 
247 o  Type  
248 o  Magnification 
249 o  Numerical aperture (NA) 
250 o  Focal length 
251 o  Working distance 
252   Auxiliary lens(es) 
253 o  Manufacturer 
254 o  Lens type 
255 o  Focal length 
256   Magnification of imaging optics: ISO 8039:2014 Optics and optical instruments 
257  Microscopes  Magnification 
258
259
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260 IV(A)(3)(b).  Test Methods 
261
262 Sponsors should conduct the following tests in conformance with the International 
263 Standards, if applicable: 
264   Relative irradiance of imaging optics at image plane per ISO 13653:1996 Optics 
265 and optical instruments  General optical test methods - Measurement of relative 
266 irradiance in the image field 
267   Distortion per ISO 9039:2008 Optics and photonics  Quality evaluation of 
268 optical systems Determination of distortion 
269   Chromatic aberrations per ISO 15795:2002 Optics and optical instruments  
270 Quality evaluation of optical systems  Assessing the image quality degradation 
271 due to chromatic aberrations 
272
273 IV(A)(4).  Mechanical Scanner Movement 
274
275 IV(A)(4)(a).  Description 
276
277 The mechanical scanner addresses the physical characteristics of the stage upon which 
278 the glass slide is affixed.  The key components include stage configuration, movement, 
279 and control.  This information is relevant whether it is only the stage that is moving and 
280 the optics are stationary, or if there is movement on all axes.  For the mechanical scanner, 
281 sponsors should provide the following information and specifications, if applicable: 
282   Configuration of the stage (a physical description of the stage) 
283 o  Stage size 
284 o  Stage manufacturer and model number 
285 o  Stage material (e.g., anodized aluminum) 
286 o  Single multi-axis or multiple stacked linear stages (manufacturer and 
287 model number) 
288 o  Type of guides or ways (e.g., bearings) 
289 o  Sample retention mechanism (slide holder) 
290   Method of movement of the stage (e.g., stepper motor, servomotor, piezomotor, 
291 etc., coupled with belt, ball-screw, lead-screw, etc.) 
292 o  Movement resolution for XY-axes  
293 o  Movement in Z-axis 
294 o  Speed range 
295 o  Travel distance 
296 o  Maximum scanning area 
297 o  Localization and reading of bar code labels 
298   Control of movement of the stage 
299 o  Open or closed loop operation 
300 o  Positional accuracy (calibration) and repeatability 
301   Lost motion compensation (e.g., backlash) 
302 o  Physical control (e.g., joystick) for single-slide, non-batch mode 
303 o  Selection of area to be scanned (in accordance to image composition 
304 software) 
305   whole slide 
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306   automatically determined area with tissue content 
307   Failure Mode and Effects Analysis (FMEA) (including severity, likelihood, 
308 mitigations, etc.) 
309
310 IV(A)(4)(b).  Test Method 
311
312 Sponsors should demonstrate the mechanical performance of the stage with respect to 
313 positional repeatability and accuracy on all relevant axes, in accordance with ISO 230-
314 2:2014 Test code for machine toolsPart 2:  Determination of accuracy and 
315 repeatability of positioning numerically controlled axes. 
316
317 IV(A)(5).  Digital Imaging Sensor 
318
319 IV(A)(5)(a).  Description 
320
321 The digital image sensor is an array of photosensitive elements (pixels) that convert the 
322 optical signals of the slide to digital signals, which consist of a set of values 
323 corresponding to the brightness and color at each point in the optical image.  Please 
324 provide the following information and specifications: 
325   Sensor type (e.g., CMOS, CCD) and manufacturer 
326   Pixel information/specifications 
327 o  Number and dimensions of pixels 
328 o  Design of color filter array 
329   Configuration of color filter array 
330   Spectral transmittance of color filter mask 
331   Responsivity specifications 
332 o  Relative response versus wavelength 
333 o  Linearity 
334 o  Spatial uniformity 
335   Noise specifications 
336 o  Dark current level (electrons per second) 
337 o  Read noise (electrons) 
338   Readout rate (e.g., pixels per second, frames per second) 
339   Digital output format (e.g., bits per pixel, bits per color channel) 
340
341 IV(A)(5)(b).  Test Methods 
342
343 Sponsors should conduct the following tests in conformance with the corresponding 
344 International Standards, if applicable: 
345
346   Opto-electronic conversion function per ISO 14524:2009  Photography  
347 Electronic still-picture cameras  Methods for measuring optoelectronic 
348 conversion functions (OECFs) 
349   Noise measurements per ISO 15739:2013 Photography  Electronic still-picture 
350 imaging  Noise measurements 
351
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352 IV(A)(6).  Image Processing Software 
353
354 IV(A)(6)(a).  Description 
355
356 Image processing software refers to the embedded software components of the image 
357 acquisition device.  It typically includes control algorithms for image capture and 
358 processing algorithms for raw data conversion into the digital image file.  Sponsors 
359 should provide the following information and specifications, if applicable: 
360   Exposure control  
361   White balance 
362   Color correction 
363   Sub-sampling 
364   Pixel-offset correction  
365   Pixel-gain or flat-field correction  
366   Pixel-defect correction 
367
368 IV(A)(6)(b).  Resources 
369
370 See the guidance entitled Guidance for the Content of Premarket Submissions for 
371 Software Contained in Medical Devices 
372 (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocument
373 s/ucm089543.htm) for the information that should be provided. 
374
375 IV(A)(7).  Image Composition 
376
377 IV(A)(7)(a).  Description 
378
379 Image composition is a step present in systems that produce whole slide images as 
380 opposed to individual fields of view.  Whole slide scanning is typically performed in 
381 accordance with the positioning of a stage that moves in submicron steps.  At each 
382 location of the stage movement, an image of the field of view is acquired.  Images can be 
383 acquired with a degree of overlapping (redundancy) between them to avoid gaps in data 
384 collection.  Images can also be acquired at different depths of focus followed by the 
385 application of focusing algorithms.  At the end of this process, all acquired images are 
386 combined (stitched) together to create a composite high resolution image.  There are a 
387 number of features that can affect this process, and they are listed below.  Sponsors 
388 should provide a description of these features, if applicable: 
389   Scanning method 
390 o  Single objective or multiple miniature objectives in an array pattern 
391 o  Scanning pattern: square matrix acquisition (tiling), line scanning, etc. 
392 o  Overlap between scanned regions  
393 o  Merging algorithms that stitch the aligned images together into a 
394 composite image file.  Such algorithms may employ functions to align 
395 adjacent fields of view in accordance to the scanning pattern, overlap, etc. 
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396 o  Automatic background correction functions to eliminate the effect of non-
397 uniformities in the microscopes illumination and image merging 
398 procedure.  These non-uniformities if not corrected might create visible 
399 borders (seams and stitch lines) between the adjacent fields of view. 
400   Scanning speed:  time to scan the whole slide.  This time is dependent on selected 
401 magnification, and the amount of tissue on the glass slide. 
402   Number of planes at the Z-axis to be digitized (stack depth) 
403
404 IV(A)(7)(b).  Test Methods 
405
406 Testing for image composition can be performed on a system level using special 
407 calibration slides (such as grid patterns) that can test for line uniformity and focus 
408 quality.  Sponsors should provide the following outputs for these tests, if applicable: 
409   Images of digitized calibration slides 
410   Analysis of focus quality metrics 
411   Analysis of coverage of the image acquisition for the entire tissue slide 
412
413 IV(A)(8).  Image Files Formats 
414
415 IV(A)(8)(a).  Description 
416
417 The final result from image acquisition can be a whole slide image consisting of a stack 
418 of all acquired fields of view and magnifications during WSI.  The complete digitized 
419 image file usually occupies between 1-20 gigabytes of storage space depending on the 
420 sample and the magnification of the objective lens used.  Images can then be stored in a 
421 number of ways and formats.  Sponsors should provide the following information: 
422   Compression method (e.g., the wavelet-based JPEG2000 compression standard or 
423 TIFF) 
424   Compression ratio:  ratio of uncompressed to compressed file size.  This metric 
425 should be provided along with descriptive information on the data it was 
426 measured from, since compression ratio is dependent on the content of the data 
427 applied to. 
428   Compression type:  lossless or lossy compression 
429   File format: can be formats easily accessible with public domain software such as 
430 JPEG or TIFF, or can be proprietary formats only accessible with specific vendor 
431 viewers.  The file format depends on the file organization and related use. 
432   For systems that interact with DICOM-compliant software and hardware, 
433 sponsors should provide a DICOM compatibility report. 
434   File organization:   
435 o  Single file with multi-resolution information (pyramidal organization) 
436 o  Stack of files at different magnifications 
437
438
439
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440 IV(A)(9).  Image Review Manipulation Software 
441
442 IV(A)(9)(a).  Description 
443
444 For the image review manipulation software, sponsors should provide the following 
445 information, describing software features, if applicable.   
446   Continuous panning (moving in x-y space) and pre-fetching (buffering adjacent 
447 images to speed up panning time) 
448   Continuous zooming (magnification)  
449   Discrete Z-axis displacement 
450   Ability to compare multiple slides simultaneously on multiple windows 
451   Ability to perform annotations 
452   Image enhancement such as sharpening functions  
453   Color manipulation, including color profile, white balance, color histogram 
454 manipulation, and color filters 
455   Annotation tools 
456   Tracking of visited areas and annotations  
457   Digital bookmarks (revisit selected regions of interest) 
458   Virtual multihead microscope (this is when multiple pathologists 
459 simultaneously review the same areas remotely) 
460
461 IV(A)(9)(b).  Resources 
462
463 See the guidance entitled Guidance for the Content of Premarket Submissions for 
464 Software Contained in Medical Devices 
465 (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocument
466 s/ucm089543.htm) for additional information on this subject. 
467
468 IV(A)(10).  Computer Environment 
469
470 IV(A)(10)(a).  Description 
471
472 Computer environment refers to the workstation, including both hardware and software 
473 components, that retrieves the digital image file and drives the display for the user to 
474 review the images.  Sponsors should provide the following information and 
475 specifications, if applicable: 
476   Computer hardware  
477   Operating system  
478   Graphics card 
479   Graphics card driver  
480   Color management settings  
481   Color profile   
482   Display interface (e.g., DVI or DisplayPort) 
483
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484 IV(A)(11).  Display 
485
486 IV(A)(11)(a).  Description 
487
488 The final stage of a WSI system is the display component that presents the scanned image 
489 to the pathologists for reading. Technically, display refers to the optoelectronic device 
490 that converts the digital image signals in the RGB space into optical image signals. For 
491 the display, sponsors should provide the following information and specifications, if 
492 applicable:  
493   Technological characteristics of the display device (e.g., in-plane switching LCD 
494 panel with TFT active-matrix array with fluorescent backlight) 
495   Physical size of the viewable area and aspect ratio 
496   For transmissive displays, backlight type and properties including temporal, 
497 spatial, and spectral characteristics  
498   Frame rate and refresh rate 
499   Pixel array, pitch, pixel aperture ratio and subpixel matrix scheme (e.g., chevron, 
500 RGBW) 
501   Subpixel driving to improve grayscale resolution (e.g., spatial and temporal 
502 dithering)  
503   Supported color spaces 
504   Display Interface  
505   User controls of brightness, contrast, gamma, color space, power-saving options, 
506 etc. via the on-screen display (OSD)  menu 
507   Ambient light adaptation including the ambient light sensing method, 
508 instrumentation, and software tool description 
509   Touch screen technology including method, functionality, and any calibration or 
510 periodical re-tuning requirements 
511   Color calibration tools (sensor hardware and associated software), color profile, 
512 and method for color management 
513   Frequency and nature of quality-control tests to be performed by the user and/or 
514 the physicist with associated action limits. 
515
516 IV(A)(11)(b).  Test Methods 
517
518   User controls: Modes and settings of the display undergoing testing should be 
519 specified, including brightness, contrast, gamma, white point, color space, etc. 
520 See 2.1 Modified-Performance Modes, IDMS 1.03. 
521   Spatial resolution: Measurements of the transfer of information from the image 
522 data to the luminance fields at different spatial frequencies of interest typically 
523 done by reporting the modulation transfer function.  Non-isotropic resolution 
524 properties should be characterized properly by providing two-dimensional 
525 measurements or measurements along at least two representative axes. See 7.7 
526 Effective Resolution, IDMS 1.03. 
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527   Pixel defects (count and map): Measurements (counts) and location of pixel 
528 defects. This is typically provided as a tolerance limit. Pixel defects can interfere 
529 with the visibility of small details in medical images. See 7.6 Defective Pixels, 
530 IDMS 1.03. 
531   Artifacts: Evaluate for image artifacts such as ghosting and/or image sticking 
532 from displaying a fixed test pattern for a period of time. See 4.6 Artifacts and 
533 Irregularities, IDMS 1.03.  
534   Temporal response: Measurements of the temporal behavior of the display in 
535 responding to changes in image values from frame to frame.  Since these 
536 transitions are typically not symmetric, rise and fall time constants are needed to 
537 characterize the system. See 10.2.3 Gray-to-Gray Response Time, IDMS 1.03. 
538   Maximum and minimum luminance (achievable and recommended): 
539 Measurements of the maximum and minimum luminance that the device outputs 
540 as used in the application under recommended conditions and the achievable 
541 values if the device is set to expand the range to the limit. See 2.4 Vantage-Point 
542 Suite of Measurement, IDMS 1.03. 
543   Grayscale: Measurements of the mapping between image values and the 
544 luminance. See 6.1 Grayscale, IDMS 1.03. 
545   Luminance uniformity and Mura test: Measurements of the uniformity of the 
546 luminance across the display screen. See 8.1.2 Sampled Vantage-Point Uniformity 
547 and 8.2.3 Mura Analysis, IDMS 1.03. 
548   Stability of luminance and chromaticity response with temperature and lifetime  
549   Bidirectional reflection distribution function: Measurements of the reflection 
550 coefficients of the display device. Specular and diffuse reflection coefficients can 
551 be used as surrogates for the full bidirectional reflection distribution function. See 
552 11.12 Diagnostic: Characterizing Hemisphere Uniformity, IDMS 1.03. 
553   Gray Tracking: Chromaticity at different luminance levels as indicated by the 
554 color coordinates in an appropriate units system (e.g., CIE uv). See AAPM Task 
555 Group 196 Report. 
556   Color scale: Color coordinates of primary and secondary colors as a function of 
557 the digital driving level and their additivity. See 6. Gray- and Color-Scale 
558 Measurement and 5.4 Color-Signal White, IDMS 1.03. 
559   Color gamut volume: See 5.31 Volume-Color-Reproduction Capability, IDMS 
560 1.03. 
561
562 IV(A)(11)(c).  Resources 
563
564 Those interested in learning more about these types of display considerations should 
565 consider reading: 
566
567   IDMS 1.03 - Information Display Measurements Standard Version 1.03, 
568 International Committee for Display Metrology, Society for Information Display, 
569 www.icdm-sid.org 
570
571   E. Samei, A. Badano, D. Chakraborty, K. Compton, C. Cornelius, K. Corrigan, 
572 M. J. Flynn, B. Hemminger, N. Hangiandreou, J. Johnson, M. Moxley, W. 
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573 Pavlicek, H. Roehrig, L. Rutz, J. Shepard, R. Uzenoff, J. Wang, and C. Willis, 
574 Assessment of display performance for medical imaging systems, Report of the 
575 American Association of Physicists in Medicine (AAPM) Task Group 18, 
576 Technical Report, AAPM (April 2005). 
577
578   IEC 62563-1:2009, Medical electrical equipment  Medical image display 
579 systems  Part 1: Evaluation methods 
580
581   Amendment 1 to IEC 62563-1: Medical image display systems  Part 1: 
582 Evaluation methods 
583
584   The guidance entitled Guidance for Industry and FDA Staff: Display Accessories 
585 for Full-Field Digital Mammography Systems-Premarket Notification (510(k)) 
586 Submissions 
587 (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceD
588 ocuments/ucm107549.htm).  
589
IV(B).  System-level Assessment 
590
591
592 This subsection details the test methods at the system level that should be included in the 
593 technical performance assessment of a WSI device.  In this guidance, system refers to a 
594 series of consecutive components in the imaging chain with clearly defined, measureable 
595 input and output.  For example, a system-level test can be designed for the image 
596 acquisition subsystem, the image display subsystem, or a combination of both.  The goal 
597 of system-level tests is to assess the composite performance of a series of consecutive 
598 components in the imaging chain.  System-level tests should be conducted when the 
599 component-level tests are either unfeasible or unable to capture the interplay between 
600 components. 
601
602 The common framework of the system-level tests described in this section is to compare 
603 the system under test with an ideal system based on the same input, and then report the 
604 difference between their outputs quantitatively.  Designing such a system-level test 
605 typically involves the following steps: (1) define the scope of the system and its input and 
606 output, (2) define the input, which in most cases is a test target or phantom, (3) measure 
607 the input to establish the ground truth that would be generated by an ideal system, (4) 
608 measure the output of the system under test, and (5) calculate the errors between the truth 
609 and the output with a quantitative metric.  The framework of a typical system-level test is 
610 shown in Diagram 2.  Notice that the ideal system is a hypothetical device that generates 
611 the perfect output with respect to the objective of the test such as color or focus.  The 
612 purpose of the ideal system is to define the intended behavior of the system under test.  
613 The ideal system does not need to be implemented.  Instead, the ideal system should be 
614 simulated by a test method that establishes the truth of the input phantom.     
615
616
617
618
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619 Diagram 2: Framework of a typical system-level test. 
620
 
621 System under test  Output 
  Input 
622  f  Error 
(Phantom) 
 
623
Ideal system  Truth 
 
624
625
626 IV(B)(1).  Color Reproducibility 
627
628 IV(B)(1)(a).  Description 
629
630 Color reproducibility is one of the key characteristics of a WSI system. The color 
631 characteristics are determined by every component in the imaging chain. Therefore, the 
632 color characteristics might be best evaluated at the system level. Color reproducibility 
633 indicates the accuracy and precision of the color transformation from the tissue sample on 
634 the slide to the image on the display. The colors of the tissue specimen should be 
635 accurately and precisely reproduced on the display based on the color reproduction intent, 
636 which should be clearly defined and justified by the sponsor. 
637
638 IV(B)(1)(b).  Test Methods 
639
640 The WSI system should be tested with a target slide. The target slide should contain a set 
641 of measurable and representative color patches. Ideally the color patches should have 
642 similar spectral characteristics to stained tissue. The color patches should include a 
643 grayscale ramp for evaluating the grayscale response. The truth of the color patches 
644 should be measured with proper apparatuses separately. 
645
646 For each color patch, the intended color (i.e., the expected output color based on the color 
647 reproduction intent defined by the Sponsor) should be calculated based on the truth of the 
648 color patches. 
649
650 The target slide should be scanned and displayed by the WSI system. The output color of 
651 each color patch should be measured from the display. 
652
653 The three datasets  truth, intended color, and output color  should be compared and 
654 analyzed. The sponsor should provide a rationale if the intended color is different from 
655 the truth.  
656
657
658
659
660
661
662
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663 Diagram 3: Framework of the system-level color reproducibility test. 
664
665
Output Color 
666 WSI under test 
667 T arget 
-  Accuracy 
668  
Slide   
Precision 
669   Color 
Truth 
670   Meter  Reproduction 
Intended Color 
671 Intent 
672
673 IV(B)(1)(c).  Resources 
674
675 Useful references on the subject of color reproducibility can be found at the International 
676 Color Consortium website http://www.color.org. 
677
678 IV(B)(2).  Spatial Resolution 
679
680 IV(B)(2)(a).  Description  
681
682 Spatial resolution is another key characteristic of a WSI system.  The goal of this system-
683 level test is to evaluate the composite optical performance of all components in the image 
684 acquisition phase (i.e., from slide to digital image file). 
685
686 IV(B)(2)(b).  Test Methods 
687
688 The following test is recommended for assessing spatial resolution of the image 
689 acquisition phase: 
690   Resolution and spatial frequency response: ISO 12233:2014(E)  Photography 
691  Electronic still picture imaging  Resolution and spatial frequency responses. 
692
693 IV(B)(3).  Focusing Test  
694  
695   The quality of focus in WSI can be affected by a number of inter-related factors, 
696 including the scanning method and approaches for constructing a focus map.  Due 
697 to a trade-off between the number of focus points and the overall speed of the 
698 scanning process, focusing is typically based on a sample of focus points, 
699 determined automatically (auto-focus) or manually by the user.  Since tissue can 
700 have uneven depth, auto-focus algorithms are needed to detect and adjust for 
701 different depths of focus.   
702
703   Data demonstrating that the focus quality is acceptable, even in the presence of 
704 uneven tissue, should be provided.  Such data with proper justification could be 
705 derived from a phantom study, from clinical data, or both in a complementary 
706 fashion.  The technology of phantom construction for testing focus is under 
707 development and this guidance will be updated as such technologies become 
708 available.  Sponsors could attempt to build their own phantoms for testing depth 
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709 of focus for their device.  Alternatively, sponsors could provide experimental data 
710 using clinical tissue slides.  Sampling of cases for such an experiment should be 
711 enriched for uneven tissue cases within a range representative of typical 
712 laboratory output.   Alternative approaches for assessing the focus quality of a 
713 WSI will be considered along with proper justification.  In addition, the following 
714 specifications should be provided, if applicable:    
715 o  Focus method: auto-focus for high-throughput or user-operated focus 
716 points  
717 o  Instructions for the selection of manual focus points (if applicable), 
718 including number of focus points and location in relation to a tissue 
719 sample 
720 o  Metrics used to evaluate focusing and description of methods to extract 
721 them 
722 o  Methods for constructing focus map from sample focus points 
723
724 Diagram 4: Framework of the system-level focusing test. 
725
726
Actual 
727 WSI under test 
Focus 
728 Phantom 
   f  Error 
729 Slide 
WSI with perfect  Optimal 
730
focusing capability  Focus 
731
732
733
734 IV(B)(4).  Whole Slide Tissue Coverage 
735
736 IV(B)(4)(a).  Description 
737
738 During the scan phase, WSI systems usually skip blank areas where tissue is absent in 
739 order to reduce scan time and file size.  The purpose of the whole slide tissue coverage 
740 test is to demonstrate that all of the tissue specimen on the glass slide is included in the 
741 digital image file.  
742
743 IV(B)(4)(b).  Test Method 
744
745 Sponsors should include a test that demonstrates the completeness of the tissue coverage.  
746 Sponsors should describe the test method and include the following items: 
747   Selection of the input tissue slide 
748   How to determine the complete coverage of the input tissue slide 
749   How to measure the actual coverage of the WSI output 
750   Calculate the ratio of the actual to complete coverage 
751
752
753
754
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755 Diagram 5: Framework of the system-level whole slide tissue coverage test 
756
757  
Actual 
WSI under test 
758  
Coverage 
759 Tissue   
   f  Error 
760   Slide 
WSI with complete  Complete 
761  
coverage capability  Coverage 
762  
763
764 IV(B)(5).  Stitching Error 
765
766 IV(B)(5)(a).  Description 
767
768 Stitching is the technique that enables a WSI system to combine thousands of sub-images 
769 into a single whole-slide image.  Although during the scanning process a certain amount 
770 of overlapping between adjacent sub-images is maintained for alignment purposes, 
771 successful stitching relies on the texture present in the overlapped area.  When the 
772 stitching algorithm fails to align two sub-images seamlessly, the error may or may not be 
773 perceivable by the human reader depending on whether noticeable stitching artifacts are 
774 generated.  Therefore, a system-level test should be conducted when assessing the 
775 stitching quality of the WSI system.   
776
777 IV(B)(5)(b).  Test Methods 
778
779 Sponsors should include a test that evaluates the stitching errors and include the 
780 following items: 
781   Selection of the input test slide 
782   Method for sampling of the stitching boundaries where stitching errors might 
783 occur 
784   How to determine the ideal stitching as the ground truth 
785 o  For example, the region of the stitching boundaries can be re-imaged in 
786 one shot such that there is no stitching artifact.    
787   How to evaluate quality of the actual stitching based on the perfect stitching 
788 o  For example, compare the image of stitching boundaries with the perfect 
789 one that does not have stitching artifact.  The difference between these two 
790 images can be used as a figure of merit of the stitching quality.  
791
792 Diagram 6: Framework of the system-level stitching error test 
793
794  
Actual 
795 WSI under test   
Stitching 
796 Tissue   
   f  Error 
797 Slide   
798   Perfect 
WSI with perfect 
799   Stitching 
stitching capability 
800  
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801
802 IV(B)(6).  Turnaround Time 
803
804 IV(B)(6)(a).  Description 
805
806 Turnaround time is the time required by the WSI system to execute a particular user 
807 operation such as panning/zooming where the software and I/O (input/output) devices 
808 retrieve image data, execute the computation, and refresh the image on the display. The 
809 turnaround time starts when the user enters a command via a keyboard stroke or a mouse 
810 click/movement and finishes when the image is completely updated on the display. 
811 Turnaround time is important for a WSI system when fast and repetitive panning 
812 operations are performed during a search task, which is delay-free in an optical 
813 microscope.  Prolonged, unpredictable turnaround time may impact the users diagnostic 
814 performance. The user interface should properly prompt the user when the operation is 
815 incomplete and the requested image is not available . The turnaround time may vary 
816 greatly depending on the user-requested operation, image content, data size/location, 
817 computer workload, display size, etc. The sponsor should report the typical turnaround 
818 time as well as the test method and test conditions.   
819   
IV(C).  User Interface  
820
821
822 IV(C)(1).  Description 
823
824 The user interface covers all components and accessories of the WSI system with which 
825 users interact while loading the slides and acquiring, manipulating, and reviewing the 
826 images.  It also includes preparing the system for use (e.g., unpacking, set up, 
827 calibration), and performing maintenance.  Elements of the user interface have been 
828 noted in many of the preceding sections and include two broad categories: 
829   Options through which the user operates the WSI system, such as:  
830 o  Software menu options (e.g., scanning parameters) 
831 o  Physical controls (e.g., clips on the slide feeder) 
832 o  Connectors and connections (e.g., cables connecting system components) 
833   Information presented to the user through  
834 o  Visual displays (e.g., scanned image, software menus) 
835 o  Sounds (e.g., tone played when scanning completed)  
836 o  Instructions (e.g., software users manual) 
837 o  Labels 
838
839 IV(C)(2).  Test Methods 
840
841 It is recommended that the analysis to identify the use-related hazards of the WSI system 
842 include the consideration of use errors involving failure to acquire, perceive, read, 
843 interpret, and act on information from the WSI system correctly or at all and the harm 
844 that could be caused by such errors.  A human factors/usability validation test should be 
845 performed to demonstrate that representative users of the WSI system can perform 
846 essential tasks and those critical to safety under simulated use conditions. 
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847
848 When selecting participants for validation testing, sponsors should carefully consider user 
849 capabilities and expectations that could potentially impact the safe and effective use of 
850 the WSI system.  Examples of items that should be considered, if applicable, include 
851 visual acuity and type of vision correction and the impact of expectations formed from 
852 prior experience with other systems (e.g., optical microscope). 
853
854 When selecting the critical tasks to be evaluated, sponsors should incorporate all known 
855 use related errors and problems from similar devices (devices having similar 
856 technological characteristics and indications for use) into the validation testing.  
857 Consideration also should be given to whether task performance changes over time, and 
858 if test duration needs to account for user fatigue.  Examples might include a user altering 
859 a task sequence in response to fatigue from repetitive image selection and manipulation 
860 with mouse or keyboard. 
861
862 When creating the simulated use conditions for validation testing, special consideration 
863 should be given to the location of the WSI system primary workstation, its components, 
864 their arrangement and how their locations affect user performance.  Examples of location 
865 considerations might include multiple monitors, a monitor with sub-optimal display 
866 settings, or glare on a monitor from indoor lighting. 
867
868 A human factors/usability validation test report should generally include the information 
869 found in Table 1. 
870
871 Table 1: Items a Human Factors/Usability Validation Test Report Should Include 
872
Section  Contents 
1  Intended device users, uses, use environments, and training  
  Intended user population(s) and critical differences in 
capabilities between multiple user populations  
  Intended uses and operational contexts of use  
  Use environments and key considerations  
  Training intended for users and provided to test participants  
2  Device user interface  
  Graphical depiction (drawing or photograph) of device user 
interface  
  Verbal description of device user interface  
3  Summary of known use problems  
  Known problems with previous models  
  Known problems with similar devices  
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  Design modifications implemented in response to user 
difficulties  
4  User task selection, characterization and prioritization  
  Risk analysis methods  
  Use-related hazardous situation and risk summary  
  Critical tasks identified and included in HFE/UE validation tests  
5  Summary of formative evaluations  
  Evaluation methods  
  Key results and design modifications implemented  
  Key findings that informed the HFE/UE validation testing 
protocol  
6  Validation testing  
  Rationale for test type selected (i.e., simulated use or clinical 
evaluation)  
  Number and type of test participants and rationale for how they 
represent the intended user populations  
  Test goals, critical tasks and use scenarios studied  
  Technique for capturing unanticipated use errors  
  Definition of performance failures  
  Test results: Number of device uses, success and failure 
occurrences  
  Subjective assessment by test participants of any critical task 
failures and difficulties  
  Description and analysis of all task failures, implications for 
additional risk mitigation  
7  Conclusion 
A statement to the effect that The <device name/model> has been 
found to be reasonably safe and effective for the intended users, uses 
and use environments should be included under the following 
conditions: 
  The methods and results described in the preceding sections 
support this conclusion.  
  Any residual risk that remains after the validation testing would 
not be further reduced by modifications of design of the user 
interface (including any accessories and the Instructions for Use 
(IFU)), is not needed, and is outweighed by the benefits that 
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may be derived from the devices use.  
873
874 Recommended methods for performing a human factors/usability validation test are 
875 described in the resources listed in section IV(C)(3) entitled Resources directly below.  
876 The goal of testing is to assure that users can operate the WSI system successfully for the 
877 intended uses without negative clinical consequences to the patient and that potential use 
878 errors or failures have been eliminated or reduced. 
879
880 IV(C)(3).  Resources 
881
882 FDA recognizes standards published by national and international organizations that 
883 apply human factors engineering/usability engineering (HFE/UE) principles to device 
884 design and testing.  The recognized standards listed below provide suggestions on 
885 conducting an analysis of use-related hazards and a human factors/usability validation 
886 test to assess the safety and effectiveness of the final device design.  
887
888   ISO 14971:2007, Medical Devices  Application of Risk Management to Medical 
889 Devices:  Provides systematic process to manage the risks associated with the use 
890 of medical devices. 
891   AAMI/ANSI HE75:2009, Human Factors Engineering  Design of Medical 
892 Devices:  Comprehensive reference of recommended practices related to human 
893 factors design principles for medical devices. 
894   IEC 62366-1:2015, Medical devices  Application of usability engineering to 
895 medical devices: Describes the process to conduct medical device usability testing 
896 and incorporate results into a risk management plan.  
897 In addition, FDA has published guidance with human factors related recommendations to 
898 assist manufacturers and facilitate premarket review.  The guidance entitled Guidance 
899 for the Content of Premarket Submissions for Software Contained in Medical Devices 
900 (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocument
901 s/ucm089543.htm).  This guidance document provides recommendations to industry 
902 regarding premarket submissions for software devices, including stand-alone software 
903 applications and hardware-based devices that incorporate software.  It includes test 
904 methods to assure that the software conforms to the needs of the user and to check for 
905 proper operation of the software in its actual or simulated use environment.  
906
IV(D).  Labeling 
907
908
909 The premarket application must include labeling in sufficient detail to satisfy the 
910 requirements of 21 CFR Part 801 and 21 CFR 809.10.  The labeling includes 
911 supplementary information necessary to use and care for the WSI system such as 
912 instruction books or direction sheets and software user manuals.   
913
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914 Although instructions, labeling, and training can influence users to use devices safely and 
915 effectively, they should not be the primary strategy used to control risk.  Modification of 
916 the user interface design is a more effective approach to mitigate use-related hazards.  
917
918 IV(D)(1).  Test Methods 
919
920 It is recommended that studies on labeling and training be conducted separately from 
921 other human factors/usability validation testing.  Human factors/usability validation 
922 testing should be conducted with the final version of the labeling and related materials.  
923 Timing and content of training should be consistent with that expected of actual users. 
924
925 IV(D)(2).  Resources 
926
927 FDA has published several guidance documents on labeling to facilitate premarket 
928 review and assist manufacturers. 
929   The guidance entitled Labeling - Regulatory Requirements for Medical Devices 
930 (http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/
931 GuidanceDocuments/UCM095308.pdf).   
932 o  This publication covers labeling issues that device manufacturers, 
933 reconditioners, repackers, and relabelers should consider when a product 
934 requires labeling.  Labeling includes adequate instructions for use, 
935 servicing instructions, adequate warnings against uses that may be 
936 dangerous to health, or information that may be necessary for the 
937 protection of users. 
938   The guidance entitled Device Labeling Guidance #G91-1 (blue book memo) 
939 (http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceD
940 ocuments/ucm081368.htm).   
941 o  This guidance is intended to ensure the adequacy of, and consistency in 
942 device labeling information.  It is intended for use by industry in preparing 
943 device labeling. 
944   The guidance entitled Human Factors Principles for Medical Device Labeling 
945 (http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/
946 GuidanceDocuments/UCM095300.pdf).   
947 o  This report presents the principles of instruction, human factors, and 
948 cognitive psychology that are involved in designing effective labeling for 
949 medical devices. 
950
IV(E).  Quality Control 
951
952
953 Sponsors should provide information on the quality control procedures, including 
954 frequency and testing methods to be performed by the laboratory technologists and/or 
955 field engineers with associated quantitative action limits.  Discussions of tests for 
956 constancy should include discussions of the slide feeder and scanning mechanisms, 
957 coverage of the entire tissue slide, the bar code reader, the light source, the imaging 
958 sensor device, and the calibrations at the component and system level.  A detailed quality 
959 control manual should be provided. 
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