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G I  
UIDANCE FOR  NDUSTRY
 
Electronic Exchange of Documents: 
Electronic File Format 
 
VICH GL53 
 
Submit comments on this guidance at any time.  Submit electronic comments on the guidance to 
http://www.regulations.gov.   Submit written comments to the Division  of Dockets Management 
(HFA-305), Food and Drug Administration,  5630 Fishers Lane, Room 1061, Rockville,  MD 
20852.  All comments should be identified  with the Docket No. FDA-2014-D-1177. 
 
For further information  regarding this document, contact Scott Fontana, Center for Veterinary 
Medicine (HFV-100), Food and Drug Administration,  7500 Standish Place, Rockville,  MD  
20855, 240-402-0656; email:  Scott.Fontana@fda.hhs.gov. 
 
Additional  copies of this guidance document may be requested from the Policy and Regulations 
Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration,  7519 Standish 
Place, Rockville,  MD 20855, and may be viewed on the Internet at either 
http://www.fda.gov/AnimalVeterinary/default.htm  or http://www.regulations.gov. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine 
September 2015 
    Contains Non-Binding  Recommendations 
VICH GL53 (EFF) - ELECTRONIC FILE FORMAT 
For implementation at Step 7 
 
 
 
 
 
 
E E D : 
LECTRONIC  XCHANGE OF  OCUMENTS
E F F  
LECTRONIC  ILE  ORMAT
 
 
 
 
 
 
 
 
Adopted at Step 7 of the VICH Process 
by the VICH Steering Committee in February 2015 
for implementation  by February 2016. 
 
 
 
 
 
 
This Guidance has been developed by the appropriate VICH Expert Working Group and has 
been subject to consultation  by the parties, in accordance with the VICH Process.  At Step 7 of 
the Process the final draft is recommended for adoption to the regulatory bodies of the European 
Union, Japan and the USA. 
 
   
2  Contains Non-Binding  Recommendations 
TABLE OF CONTENTS 
 
1  INTRODUCTION ........................................................................................................ 4 
1.1  Objective ............................................................................................................4 
1.2  Scope..................................................................................................................4 
1.3  Basic Principles...................................................................................................5 
2  Portable Document Format (PDF) File Format............................................................ 6 
2.1  Single-file transfer...............................................................................................6 
2.2  Multiple-file transfer ......................................................................................... 10 
2.3  Best-practice recommendations ......................................................................... 11 
3  Other File Formats ..................................................................................................... 15 
4  References ................................................................................................................... 16 
   
3  Contains Non-Binding  Recommendations 
Guidance for Industry 
 
Electronic Exchange of Documents:  
Electronic File Format 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the 
title page. 
 
1  INTRODUCTION 
 
1.1  Objective  
 
The electronic exchange of regulatory documents concerning veterinary medicinal  products 
between industry and regulatory authorities is commonplace.  Global harmonization  of the 
specifications for the electronic file format of documents is seen as a fundamental starting point 
to realizing  the potential benefits. 
 
FDAs guidance documents, including  this guidance, do not establish legally enforceable 
responsibilities.   Instead, guidances describe the Agencys current thinking  on a topic and 
should be viewed only as recommendations,  unless specific regulatory or statutory 
requirements are cited.  The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required. 
 
1.2  Scope 
 
The scope of this guidance is to cover the electronic file format specifications for individual 
documents and collections  of multiple  related documents that do not need subsequent 
modification  during the regulatory procedure and are utilized  for electronic exchange between 
industry and regulatory authorities in the context of regulatory approval of veterinary medicinal 
products.  It applies to communication  or data exchanged as documents in the context of all 
regulatory procedures where regulatory authorities accept electronic transfer of such documents.  
This may include but is not limited  to applications  for initial  marketing authorizations,  related 
pre-submission  or post-authorization  procedures, applications  for maximum  residue limits, 
clinical  trial applications,  drug / active substance master files or requests for regulatory or 
scientific advice, etc. (depending  on a regional legislative  situation). 
 
This guidance provides different options and specific recommendations related to the electronic 
format of exchanged files.  Following  the recommendations  outlined  in this guidance will  help 
ensure that electronic files are suitable and appropriate for regulatory review but will also 
involve  complying  with specific IT requirements. 
 
4  Contains Non-Binding  Recommendations 
Working documents that need to be maintained  in their native file format for further editing  (e.g., 
Microsoft (MS) Word), such as proposed label texts, are outside the scope of this guidance. 
 
An implementation  period of one year after adoption  of the guidance is recommended.  
However, it may be voluntarily  applied earlier where electronic exchange of documents within 
the scope of this guidance is already accepted by regulatory authorities at the time of adoption of 
this document. 
 
For business processes that are still paper-based, implementation  of this guidance may be 
suspended by regulatory authorities until  electronic exchange can be accepted. 
 
Specific recommendations may apply to country-/region-specific  documents, for example, 
application  forms or facsimile copies of labels for use in the country or region. 
 
The guidance is addressed as a guidance document to industry;  however, voluntary acceptance of 
the principles  of this guidance for documents created by regulatory authorities for exchange with 
industry is also encouraged. 
 
1.3  Basic Principles 
 
A standard interchange file format for documents that do not need to be modified  or extracted 
into databases should fulfill  the following  basic principles: 
 
  can be generated from other electronic source formats or digitized  from paper; 
  is designed for viewing and/or printing; 
  allows the use of a document viewer whose specifications are in the public domain; 
  relies on major international standards like those of the International Organization  for 
Standardization  (ISO); 
  is both device and resolution  independent; 
  retains the content and the layout of the original  document; 
  remains useable and accessible long-term; 
  preserves the visual appearance of file content over time; 
  supports regulatory review needs, including  searchable text; 
  builds on a format that already has broad acceptance among industry and regulatory 
authorities; 
  is a cost-efficient solution  for the veterinary sector. 
 
   
5  Contains Non-Binding  Recommendations 
2  Portable Document Format (PDF) File Format 
 
The following  sections address: 
 
  File format specifications for single files (section 2.1) and additional  specifications  for 
hyperlinked  files (section 2.2).  These specifications may be used as basis for establishing 
pass / fail criteria, i.e., rejection of incompliant  files. 
 
  Best practices, which significantly  enhance the review process, but which should not be a 
ground for rejection of files (section 2.3). 
 
When following  the single file specifications detailed in section 2.1, two options are available: 
 
  Option 1 describes PDF/A-compliant files. This is the easiest way to comply with these file 
format specifications.  Simply  saving a single document as PDF/A file using any PDF/A-
compliant  software does automatically  cover most file format specifications. 
 
  Option 2 describes a minimum  set of specifications  for PDF files without formal PDF/A 
compliance.  This option may for example be preferable in a transition phase, during which 
submitting  applicants are not yet ready to produce fully PDF/A-compliant files. 
 
Publications  should, where possible, follow the format specifications of option 1 or option 2.  As 
they are public source documents and different restrictions for long-term storage appear to be 
acceptable, these files are exempted from the application  of criteria beyond PDF version and file 
integrity. 
 
2.1  Single-file transfer 
 
Option 1: PDF/A-conforming files: 
 
A standard interchange format for electronic transfer of documents that follow the principles  as 
set out in section 1.3 is PDF/A, which restricts PDF in a way that it is optimized  for exchange 
and long-term reproducibility  of the content. 
 
PDF files that conform to [ISO-19005-1:2005],  [ISO-19005-2:2011]  or [ISO-19005-3:2012] are 
accepted for all types of electronic exchange of non-editable  documents between industry and 
regulatory authorities.  Note, however, that the use of embedded files or PDF portfolios  / PDF 
packages, though they may conform to the PDF/A ISO standard, is not adequate for regulatory 
review (see table below and section 2.3 for further details). 
 
Minimum  PDF/A conformance level, i.e., Level B conformance (PDF/A-1b, PDF/A-2b or 
PDF/A-3b) is sufficient and is also recommended as this level is the easiest to comply with. 
Compliance with higher levels of PDF/A conformance such as Level A or Level U is not 
necessary but such files will be accepted as well. 
 
The specification is available from the ISO web site: http://www.iso.org/. 
 
6  Contains Non-Binding  Recommendations 
It is important to note that the PDF/A ISO standard also specifies that the application  (PDF 
reader) that is reading and processing PDF files complying  with a specified conformance level, 
should comply with all relevant specifications as detailed in [ISO-19005] to ensure that the 
document is correctly displayed or printed. 
 
Note that the PDF/A specification  alone cannot ensure that the visual appearance of the content 
accurately reflects the original  source material used to create the conforming  file. 
 
Applicants therefore should control the process used to create a conforming  file to ensure that a 
PDF/A file is an accurate visual representation of the original  source document.  Potential issues 
to be observed are incorrect or missing characters caused by inappropriate  font substitution,  or a 
negative impact on quality of images due to inappropriate down sampling  or poor  e.g., maxium 
lossy - compression.  Applicants should also be aware that the quality of elements like graphics 
is already determined within the authoring software (e.g., the word processing software used). 
 
Option 2: Minimum  specifications for non-PDF/A conforming  files: 
 
Where a document does not conform to the PDF/A ISO standard, applicants should observe the 
following  minimum  specifications. These should be followed to ensure that it is adequate for 
regulatory review, to increase long-term sustainability  and to ease a potential  conversion process 
to an archive format (i.e.,PDF/A) and therefore also make reference to some important PDF/A 
specifications. 
 
Feature  Specification  Comment 
PDF Version  Files have been created and  Based on [ISO 32000-1:2008]  Document 
saved as PDF 1.4, 1.5, 1.6, or  management -- Portable document format -- 
PDF 1.7.  Part 1: PDF 1.7. 
 
Use of PDF Extension Levels to version 1.7 
does not lead to rejection / invalidation  of 
files. 
7  Contains Non-Binding  Recommendations 
Feature  Specification  Comment 
Security  No type of security on  Password protection preventing access to the 
settings  individual  files.  document or restricting permissions,  e.g., to 
prevent printing  or the copying of text, is not 
allowed. 
 
Documents which may not be able to be 
stripped of all security settings are exempted.  
This includes references taken from journals 
and other publications  or PDF forms provided 
by regulatory authorities. 
 
To provide a secure mechanism for exchange 
of confidential  information  between 
applicants and regulatory authorities the use 
of appropriate tools like secure web portals or 
secure gateway-to-gateway communication  is 
recommended.  PDF files in such cases 
should not be password-protected for reasons 
of security.  Password-protected, encrypted 
ZIP or PDF files should be used only in case 
of unprotected transfer (e.g., via email) and if 
agreed between applicant and receiving 
authority.  Note that encrypted PDF files 
cannot be converted to PDF/A.  Please 
consult guidance of national/regional 
authorities concerning available methods for 
file transfer. 
Prohibited  PDF files do not contain:   
PDF features 
    JavaScript and executable  Region-specific  documents like electronic 
file launches  application  forms with JavaScript 
functionality  provided by regulatory 
authorities are exempted. 
    External content references  Note that external hyperlinks  to other PDF 
(Everything needed to  documents if used in a multi-file  submission 
render or print a PDF file  (see section 2.2) or to web pages are in 
must be contained within  conformance with the PDF/A ISO standard.  
the file.) 
    Dynamic content which can   
include audio, video, 3D 
content or other special 
effects and animations 
8  Contains Non-Binding  Recommendations 
Feature  Specification  Comment 
    Attachments (embedded  Embedded files are not adequate for 
files)  regulatory review as they can be easily 
overlooked during compilation  / review of 
documents and may complicate technical 
validation. 
Font  Every font used for visible  text  The PDF/A ISO standard requires embedding 
embedding  should be embedded within the  of fonts used for rendition  of visible text only.  
PDF file.  Thus invisible  fonts used in scanned 
documents for creating searchable text by an 
Optical Character Recognition  (OCR) routine 
may be embedded but are exempted from the 
embedding requirement of the ISO standard. 
 
The PDF/A ISO standard requires only 
embedding of the subset of characters actually 
used in a given font.  Embedding complete 
fonts needlessly increases the size of the PDF 
file. 
 
All embedded fonts must also be legally 
embeddable, i.e., license agreements must 
allow unlimited  embedding  into the PDF file, 
either fully or as a subset, for the purpose of 
printing  or viewing  the document.  Subsetting 
and use of commonly  used fonts is 
recommended from a copyright perspective. 
9  Contains Non-Binding  Recommendations 
Feature  Specification  Comment 
File integrity  Files must not be corrupted.  For technical validation  a check may be 
achieved by opening a file in a PDF reader 
which is compliant  to [ISO 32000-1:2008].   If 
the file opens without error, the PDF file is 
considered to be conformant. 
 
Note that this method may not detect all 
possible errors within a file.  To avoid delays 
in the review process the applicant should 
carefully check file integrity before transfer, 
again preferably using a standard-compliant 
reader.  Browsing the complete document 
page by page will assure that the full content 
is accessible. 
 
In combination  with above technical PDF 
check by regulatory authorities,  this simple 
manual check effectively assures that a 
reviewer can fully access all received 
documents. 
 
2.2  Multiple-file transfer 
 
In case of transfers of multiple  documents some regulatory authorities recommend or even 
request the use of inter-document  hyperlinks  to other PDF files to improve the efficiency of 
navigating  through such submissions. 
 
Note that inter-document  hyperlinks  may become non-functional  when files are maintained 
within a regulatory authoritys document management system which does not support inter-
document hyperlinks.   Therefore, the applicant should consult relevant guidance from 
national/regional  authorities to avoid investing  resources into hyperlinks  when the applicant has 
to submit only to regulatory authorities that are not able to benefit from such improved 
navigation. 
 
Note that external hyperlinks  to other documents in a submission  in principle  are in conformance 
with the PDF/A ISO standard.  Where PDF/A is used, authors however should observe that 
specific hyperlink  actions are forbidden in [ISO-19005] (see section 2.3 for further details), and 
reviewers may need to configure ISO compliant  readers to make external hyperlinks  actionable. 
 
When such inter-document hyperlinks  are requested, in addition  to section 2.1, the following 
specifications apply: 
   
10  Contains Non-Binding  Recommendations 
 
Feature  Specification  Comment 
Inter- Destination  To maintain  the functionality  of hyperlinks,  inter-document 
document  file path  hyperlinks  or bookmarks should refer to other PDF files by using 
hyperlinks  or  relative file paths and all files should remain in the same relative 
bookmarks  location in a folder structure after hyperlinking. 
 
To allow reading on certain devices, using non-Windows 
operating systems, hyperlinks  and bookmarks should be 
configured as specified in [ISO 32000-1:2008].   Specifically  the 
paths should use forward slashes.  Consult the PDF 
specifications as in [ISO 32000-1:2008],  section 7.11.2.3 for 
further detail.  Please note, that some PDF tools display the path 
for the link with backslashes, though the link in the PDF file is 
fully conforming  to these ISO specifications.  Open the PDF file 
with a simple text editor or validate with an appropriate tool to 
confirm conformance in case of doubt. 
 
2.3  Best-practice recommendations 
 
There are additional  features that are considered good practice for preparation of regulatory 
relevant documents. PDF files that are not in conformance with such practice will not be rejected 
by regulatory authorities; however, applicants are reminded that following  these best practices 
will significantly  enhance the efficiency of any review process. 
   
11  Contains Non-Binding  Recommendations 
 
Feature  Recommendation 
File size  File size of a single file should be limited  to 100 MB. 
Fonts  It is recommended to use fonts that are used by most text processors like 
Arial, Courier and Times New Roman or other fonts with similar level of 
usage. No customized fonts should be used. 
 
Use an adequate font size that ensures legibility. 
 
Use black font color for normal text.  Blue font may be used for hypertext 
links. 
 
For languages not based on Latin Characters like Japanese an appropriate 
multi-byte  character font supporting  Unicode should be used. 
Graphics / Images  When creating PDF files containing  graphics or images, use lossless 
compression until the final rendition  is created. Alternatively use the most 
limited  / highest-quality  lossy compression that does not compromise 
visual quality. 
 
For files containing  color images / color photos consider a color model 
based on RGB.  As sRGB (standard RGB color space as specified in 
[International Electrotechnical  Commission  (IEC) 61966-2-1]) is the 
native color space for usual source applications,  operating systems and 
most digital  cameras and scanners, this avoids conversion to another color 
model and potential negative impact on image fidelity. 
12  Contains Non-Binding  Recommendations 
Feature  Recommendation 
Hyperlinks +  Intra-document hyperlinks  and bookmarks should be used to assist the 
bookmarks (general  reviewers in navigating  through the content of a submitted document. 
recommendations)  
Where recommended by regulatory authorities, inter-document  hyperlinks 
and bookmarks should be used to assist the reviewers in navigating 
through the content of a multi-file  submission. 
Text hyperlinks  should be visibly  distinct from other text (e.g., blue text 
may be used). 
When creating bookmarks and hyperlinks,  the magnification  setting 
should be set to Inherit Zoom. 
Where bookmarks are used the initial  view of the PDF file should be set 
as Bookmarks Panel and Page. 
Hyperlinks to web pages may be used if they are active and the 
destination  is given as a valid web address, also known as uniform 
resource locator (URL).  All URLs should be displayed  as a fully 
qualified  URL such as: http://www.vichsec.org/. 
 
As URLs may change after preparation of a document, hyperlinks  to web 
pages should however not be used for any content relevant for the 
assessment of the transferred file(s).  In such cases a PDF rendition  of the 
page(s) should be created and submitted as a separate document. 
13  Contains Non-Binding  Recommendations 
Feature  Recommendation 
Hyperlinks from  When setting hyperlinks  between PDF documents, in the PDF writer the 
PDF to PDF files  link action to jump to a page view of another (remote) PDF file should 
be chosen.  Technically this is known as a Remote Go-To Action.  An 
action to open another file should not be chosen. 
Technical background:   Because JavaScript and executable file launches 
are forbidden in [ISO-19005], a hyperlink  cannot be made by such means.  
Such hyperlinks  may also be lost during PDF/A creation.  Instead, 
hyperlinks  should be provided as specified in [ISO 32000-1:2008], 
section 12.6.4.3 Remote Go-To Actions (GoToR). 
In case of doubt, use of correct hyperlinks  parameters can be confirmed 
with the help of a simple text editor. 
Hyperlinks to other  In exceptional cases, hyperlinks  to open a file of a different file format 
destination  file  may be provided  (e.g., to graphic files as specified in section 3 or to an 
formats  MS Word file).  When setting hyperlinks  to non-PDF documents, in the 
PDF writer the link action to open a web page should be chosen to enter 
the Uniform Resource Identifier (URI) of the destination  file, i.e., the full 
name and where applicable the destination  file path. Technically  this is 
known as an URI Action.  Note that, in addition,  the recommendations 
of section 2.2 for file paths apply. 
 
Technical background:  Note that hyperlinks  based on a Launch Action 
(see [ISO 32000-1:2008],  section 12.6.4.5) are not allowed in [ISO-
19005].  Such hyperlinks  may also be lost during PDF/A creation.  
Therefore hyperlinks  to other file formats should use the URI action as 
specified in [ISO 32000-1:2008],  section 12.6.4.7 URI Actions. 
Page numbering  Pages within an individual  file should be numbered.  The initial  page of 
the source document and PDF document should be numbered page 1. 
Page orientation  Pages should be properly oriented.  For example, you should set the page 
orientation  of landscape pages to landscape prior to saving the PDF 
document in final form to ensure correct page presentation. 
Page view settings 
Use default initial  page view settings for page layout and magnification.   
PDF portfolio  / PDF  The use of PDF portfolios  is in conformance with the PDF/A ISO 
package (portable  standard.  Nevertheless use of such PDF collections  should be avoided as 
collections)  its functionality  may rely on presence of other software and thus may 
cause issues during the review process. 
14  Contains Non-Binding  Recommendations 
Feature  Recommendation 
Print area  Ensure that sufficient page margins and readability are maintained in 
printouts,  regardless of whether ISO 216:2007  A4 (210 x 297 mm) or a 
Letter format (8.5 inches by 11 inches) sheet of paper is used for printing. 
 
This may be achieved either by a smaller print area using only the 
overlapping  area of both formats (allowing  printing  without resizing),  or 
by appropriate formatting of the document to ensure its readability  is not 
adversely affected by resizing to the other format, e.g., by using 
sufficiently  large font sizes. 
 
Files used for local/regional  submission  only (including  mock-ups) are 
exempted. 
Resolution  of  If scanning is unavoidable  the following  scanning parameters should be 
scanned elements  used: 
Scanning of text documents at a resolution  of not less than 300 dots per 
inch (dpi) will  normally balance legibility  and file size. Higher resolution 
may be required for scanned graphics. 
When saving scanned documents, lossy compression should only be used 
with caution as it might compromise legibility.   For example, visible 
artifacts may be created around complex high-contrast image areas like 
text.  Therefore, such images are unsuitable for lossy compression, as 
opposed to continuous-tone  photographic images. 
Source format  PDF files should be created (rendered) directly from their electronic 
source documents, except where the applicant has no access to the 
electronic source document. 
 
In addition,  care should be taken in the settings defined for the PDF writer used to ensure that no 
device-specific options are embedded in the PDF file (i.e., for a specific physical output device 
like a printer) as the file format should be device-independent. 
 
3  Other File Formats 
 
The default file format for narrative documents that need no subsequent editing  is PDF. This 
recommendation  applies likewise to graphic documents.  However, in exceptional cases when 
appropriate for review purposes, the following  file formats may also be used: 
 
  Joint Photographic Experts Group (JPEG), 
  Scalable Vector Graphics (SVG), 
  Graphics Interchange Format (GIF) and 
  Tagged Image File Format (TIFF) [ISO 12234-2:2001]. 
 
15  Contains Non-Binding  Recommendations 
4  References 
 
[IEC 61966-2-1:1999]  Multimedia  systems and equipment  Colour measurement and 
management  Part 2-1: Colour management  Default RGB colour space  sRGB. 
 
[ISO 12234-2:2001]  Electronic still-picture  imaging -- Removable memory -- Part 2: TIFF/EP 
image data format. 
 
[ISO-19005-1:2005]  Document management -- Electronic document file format for long-term 
preservation -- Part 1: Use of PDF 1.4 (PDF/A-1). 
 
[ISO-19005-2:2011]  Document management -- Electronic document file format for long-term 
preservation -- Part 2: Use of ISO 32000-1 (PDF/A-2). 
 
[ISO 19005-3:2012]  Document management -- Electronic document file format for long-term 
preservation -- Part 3: Use of ISO 32000-1 with support for embedded files (PDF/A-3). 
 
[ISO 32000-1:2008]  Document management -- Portable document format -- Part 1: PDF 1.7.1 
 
                                              
1 An ISO approved copy of the ISO 32000-1 standards document is available as a free PDF on the Adobe Web site 
(http://wwwimages.adobe.com/www.adobe.com/content/dam/Adobe/en/devnet/pdf/pdfs/PDF32000_2008.pdf). It is not an 
official ISO document but the technical content is identical and page and section numbers are preserved. 
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