Creating an FDA-compliant PDF document for regulatory submission is a critical step in ensuring that your submission is acceptable for FDA review. Read on for a guide that breaks down the key steps.
FDA Compliant PDFs Start During Authoring
FDA Compliant PDFs shouldn’t be an afterthought left to your Submission Readiness team to sort out. There are a couple of things you can do to increase efficiency and reduce the potential for rework.
Start With Templates
One of the easiest ways to ensure you have compliant PDFs is to start with Microsoft Word templates that use standard fonts (Times New Roman, Arial and Courier) and consistent styles built in. When a document author uses built-in styles, captioning features, and internal cross-reference functionality, it makes the conversion to PDF much easier because those components will generate bookmarks and internal hyperlinks. This is a great step toward increasing efficiency in your submission readiness process.
Update Fields
Before you convert your Word document, you should make sure all fields have been updated, including the Table of Contents. This should ensure all table, figure and section references are updated to reflect the final numbering. This will also alert you to any “broken” references. If you search for “Error!” you’ll be able to find and correct any references that weren’t able to be resolved. (This typically happens when a section, table or figure was deleted, but the in-text cross-reference wasn’t updated.)
Converting Word Documents Into FDA Compliant PDFs
During conversion, there are a number of things you should do to ensure FDA compliance.
Use the Correct PDF Version
The FDA requires that PDFs for submission should be in version 1.4, 1.5, 1.6, or 1.7, as newer or outdated versions may cause compatibility issues. Anything higher or lower than those versions will cause a low validation error. While this is unlikely to cause a technical rejection, it does increase the risk of compatibility issues which would trigger a remediation request from the agency.
Optimize File Size
Large file sizes can slow down the FDA's review process. It's important to reduce the file size without sacrificing quality. The FDA recommends avoiding excessive resolution for images (300 DPI for color and grayscale, 600 DPI for black and white images is typically sufficient).
Ensure Document Accessibility
The FDA expects that all PDFs submitted are fully searchable and accessible. When a document is converted to PDF from Microsoft Word (or a similar program), this should happen automatically. This is the preferred method for PDF creation. However, sometimes documents are only available as a scanned PDF, whether because they have a wet ink signature or because they are older documents and no source Word files are available. In these instances, scanned documents must undergo Optical Character Recognition (OCR) to convert them into searchable text.
Embed Non-Standard Fonts
If you’re using any fonts that aren’t standard, you’ll need to ensure they are fully embedded, not just subsets.
Avoid Restricted Features
Certain features, such as password protection, encryption, or digital rights management (DRM), are not allowed in FDA submissions. These features can prevent access to important sections of your submission or delay its review. Make sure the document is accessible without any restrictions.
Ensuring PDFs are FDA Compliant After Conversion
Once a Microsoft Word document has been successfully converted to PDF (or a document has been scanned and OCR’d), there are a few steps left to ensure FDA compliance.
Hyperlinks and Bookmarks
If a template was properly used, the PDF should now have properly placed internal hyperlinks and bookmarks that are vital for ease of navigation in lengthy submissions.
If a PDF was converted without bookmarks (e.g., when a scanned document was used) and is at least 5 pages, then the PDF should be bookmarked according to the table of contents or section headings to ensure easy navigation.
If external hyperlinks (i.e., hyperlinks that go from one document to another) need to be added, they should be relative, not absolute, which ensures they remain functional when a submission is transferred to a different device. External hyperlinks should also be set to open in a new window.
Lastly, all bookmarks and hyperlinks should be set to inherit zoom.
FDA reviewers rely on bookmarks and hyperlinks to move through complex documents efficiently, so they should be used judiciously to reference other sections, appendices, or external sources.
Set or Confirm Open Settings
Last but not least, the PDF open settings should be set to Default magnification and layout. If the PDF has bookmarks, the Navigation tab should be set to Bookmarks Panel and Page. If the document has no bookmarks, then it should be set to Page Only.
Confirm PDF Version and Fast Web View
To ensure compliance after modifying a PDF, the document should be re-optimized to ensure a compliant PDF version is used and that the document is saved using the Fast Web View setting.
Conclusion
Creating an FDA-compliant PDF document involves paying attention to formatting, accessibility, and navigability details as outlined in the FDA’s PDF Specifications Guidance. By following these steps, you'll ensure that your submission meets FDA expectations and avoids unnecessary delays during the review process.
If your team is overwhelmed with submission readiness tasks, especially leading up to a major submission like an IND, NDA or BLA, The Sugar Water Operations Team can help! Our submission readiness experts can step in on a short-term basis to get you ready for your big deliverables. Reach out today to chat about how we can help you meet your goals.