By Mary Waters, Senior Consultant, eCTD Publish Services

Noun; a link from a hypertext file or document to another location or file, typically activated by clicking on a highlighted word (typically blue colored text) or an image on the screen. There is a method to the madness and thought processes associated with the blue colored text for hyperlinks. You can read more about the history of hyperlinks and how the blue text was selected in the Hyperlink Usability: Guidelines for Usable Links (Naji, 2016).

Hyperlink(s) is(are) a reference point to data that the reader can directly follow by clicking, tapping, or hovering. A hyperlink can point to a whole document or just to a specific part within a document.

Hypertext is text with hyperlinks. The text, that is linked from is called the anchor text.

Both internal and external links allow users of the website to navigate to another web page or resource. Users can navigate from one resource to another by clicking on hyperlinks. Internal links help users navigate the same website, whereas external links generally take users to a different webpage or website.

In the eCTD world, there are a few rules that make reviewing documents easier and therefore, with less trouble for your FDA Reviewer. In most submissions, your FDA Reviewer will find many hyperlinks. Here are some best practices that apply to hyperlinks and how to use or apply them in your documents.

  1. Standard practice as per US, EU or other country guidelines typically link to the first reference on the page; and does not link for duplicates found on the page (you would only link the first one on that page as the reviewer can use that link over and over). As with cross-references and destinations located on the same page, you don’t have to link those two together.
  2. For every link in your document, when pointing to or from the same or different document, these links do need to be checked – each one needs to work properly!
  3. Using designated “styles” for your headings, tables and figure captions with the Microsoft Word “insert cross-reference” tool will facilitate the publishing process. When using this tool, the references are automatically updated as your document changes, and hyperlinks are automatically created when you convert to PDF. Tip: be sure to create the heading, table, page number, etc. before creating the link.
  4. Links could be generated automatically using Word PDF Maker or Adobe Pro for internal links and automatically linked in the publishing tool for external links.
  5. Links need to be obvious; reviewers do not want to interact with the interface to find the links.
  6. Pick or create a hyperlink design (style) and make it consistent throughout all of your documents (e.g. font name, Calibri; size 12 pt; colors R-0, G-0, B-255; update the hyperlink style to reflect changes and make the changes default).
  7. It’s helpful for links to change colors after they have been clicked (changing from blue to purple). This helps the reviewer to know when a link has been used.
  8. To emphasizes that the links are clickable, make sure the style changes with mouse-overs.
  9. Don’t use “click here” for the hyperlink text; reword so that the linked word(s) match the title of the destination (paragraph, page, form, etc.)

Hyperlinks and Validation Errors

Listed below are a few of the hyperlink validation errors that might be returned with improperly applied hyperlinks. Some of these links are more problematic than others (high, medium, low). It’s best practice to fix every one that you can before submitting through the ESG.

Broken Hyperlink (number 5200, medium): Documents with one or more hyperlinks pointing to a file that does not exist.

Non-existent Named Destination or Page (number 5202, medium): This is a document with one or more hyperlinks pointing to a “named” destination or page that does not exist.

Corrupt Link (number 5201, medium): One or more documents pointing to a file that cannot be opened.

Multiple Action Hyperlink (number 5203, medium): Links that contain one or more (multiple) actions.

External Hyperlink (number 5205, medium): Web references in a hyperlink (web links, email links); external but do not open in “new window”.

Inactive Hyperlink (number 5210, medium): Document that has one or more inactive links that are functioning.

Non-relative Hyperlink (number 5215, medium): Document that has one or more non-relative (absolute) hyperlinks.


If you’re still having issues with your hyperlinks, let us help you validate them. We’re just an email or phone call away.


Hyperlink Usability: Guidelines for Usable Links


US FDA, eCTD Validation Criteria



Nitisha Pyndiah - Biotech Consulting Services

Mary is an expert provider of electronic Common Technical Documents (eCTD) publishing services. Since joining HW in 2016, Mary has submitted over 225 electronic submissions through the FDA ESG.