How to Prepare PDFs for Regulatory Submissions (eCTD)

To prepare PDFs for regulatory submissions, create them from electronic source files, use an accepted PDF version, embed fonts, keep text searchable, add bookmarks and working hyperlinks, remove passwords and security settings, keep each file within size limits and optimise it for fast web view. The detailed rules come from each agency's current specification.

This checklist is based on three primary documents: the FDA's Portable Document Format (PDF) Specifications (version 4.1, September 2016, the version listed in FDA's eCTD Submission Standards catalogue when we checked), the EMA's Harmonised Technical Guidance for eCTD Submissions in the EU (version 6.0.1, June 2025), and Appendix 7 of the ICH eCTD Specification v3.2.2. These documents are revised over time, and sponsors must follow the current version of each agency's specification. This article is general guidance, not regulatory advice.

Which PDF version should you use?

The FDA accepts PDF versions 1.4 through 1.7, PDF/A-1 and PDF/A-2. The EMA guidance lists the same versions, recommends PDF/A where possible, and states that PDF 1.3 or earlier is not acceptable. You can see a file's PDF version in the document properties of most PDF readers.

The FDA specification also says submitted PDFs must not contain JavaScript, dynamic content such as audio or video, attachments or 3D content, and should not include PDF annotations, with exceptions for promotional material. The EMA guidance says PDFs should not be submitted as a PDF Portfolio.

Are all fonts embedded?

The FDA asks for all non-standard fonts to be fully embedded, with all characters of each font included rather than a subset. The EMA asks for fonts to be embedded where possible. The FDA recommends font sizes from 9 to 12 point, with Times New Roman 12 point for narrative text and 9 to 10 point for tables.

Check embedding in your PDF reader's document properties, usually on a Fonts tab. Font embedding is set when the PDF is created, so if a font is missing, fix it in the source document and your PDF creation settings, then create the PDF again.

Is the text searchable?

Both agencies want text you can search and copy. The FDA says to avoid image-based PDFs whenever possible, to make scanned files text searchable where possible, and to verify that optical character recognition (OCR) has converted the text completely and accurately. The EMA says documents should, wherever possible, be produced from a text source, and that scanned documents should normally include OCR. It lists exceptions, such as GMP certificates, certificates of analysis and pages that contain only a signature.

For scans you cannot avoid, the FDA and ICH documents recommend 300 dpi for typical black and white text. OCR PDF adds an invisible text layer to scanned pages in your browser; proofread the result, as the FDA expects. Our guide on making a PDF searchable with OCR explains the steps.

Do documents have bookmarks and working hyperlinks?

The FDA asks for a hyperlinked table of contents and bookmarks in documents of five pages or longer, a bookmark hierarchy identical to the table of contents, up to four levels deep, and bookmarks and links set to "Inherit Zoom". It also recommends relative paths for links between files, because absolute links to specific drives stop working once a submission is loaded onto agency servers. The EMA guidance quotes ICH: any document with a table of contents is expected to have bookmarks.

Bookmark PDF lets you add, edit and import bookmarks, and Bookmarks Auto Generator suggests bookmarks from heading font sizes and numbering patterns. Both create bookmarks that keep the reader's current zoom level. Review auto-generated bookmarks against the table of contents before use, and set hyperlinks and the initial view (FDA: "Bookmarks Panel and Page") in your publishing software.

How large can each PDF be?

Appendix 7 of the ICH eCTD Specification v3.2.2 states that PDF files should be no larger than 100 megabytes. Check the current regional guidance for any other limit that applies to your submission.

To reduce size, Compress PDF offers Standard and Condense modes, which keep text and links. Avoid its Photon mode for submission documents: it converts pages to images, which removes searchable text and can lose links. The FDA recommends lossless image compression (Zip/Flate or CCITT Group 4) and warns against resampling scans to a lower resolution, so check images remain legible afterwards. See how to compress a PDF for more.

Have all passwords and security settings been removed?

The FDA says not to activate security settings or password protection, and that FDA forms should be submitted with the security settings they come with. The EMA says there must be no security setting to open any file, and no security settings on individual files except in Modules 1.0, 1.2, 3.3, 4.3 and 5.4; where settings cannot be removed, for example on digitally signed documents, printing and content copying must at least be allowed.

For documents you are authorised to change, Decrypt PDF removes an open password when you enter it, and Remove Restrictions removes permission restrictions such as blocks on printing or copying. Either rewrites the file, which can invalidate an existing digital signature. If you protected a draft yourself, our guide on password protecting a PDF explains the settings involved.

Are page size and orientation right?

The FDA asks for the print area to fit 8.5 by 11 inch paper, with a left margin of at least three quarters of an inch and at least three eighths of an inch on the other sides, and notes these margins also allow printing on A4. The ICH specification asks for pages to fit both A4 and Letter. Both ask for landscape pages to be saved in landscape orientation.

Page Dimensions reports each page's size and orientation. Fix Page Size can standardise pages to A4 or Letter, but scaling shrinks content, so check that text stays within the FDA's recommended font sizes.

Is the file optimised for fast web view?

The FDA, EMA and ICH documents all ask for PDFs to be optimised for fast web view, also called linearisation. Linearize PDF linearises files with the open-source qpdf engine running in your browser. Make it the final step, because later changes can undo the optimisation.

A final checklist

1. PDF version 1.4 to 1.7, PDF/A-1 or PDF/A-2.
2. Created from electronic source; scans OCRed and proofread.
3. All non-standard fonts embedded.
4. Bookmarks and hyperlinks working, with relative paths between files.
5. Each file within the size limit that applies.
6. No passwords or security settings, apart from agency exceptions.
7. Correct page size, margins and orientation.
8. File names in lower case, without spaces or special characters other than hyphens and underscores, as the FDA asks.
9. Optimised for fast web view as the last step.

Priya LifePDF can help with individual steps, and it processes files in your browser without uploading them. It is a general-purpose tool, not a validated GxP or eCTD publishing system, and its output is not certified against any agency specification. Your publishing team's validated tools and checks remain the final word.