Submission Document Granularity - By Scott Cleve

Submission Document Granularity
by Scott Cleve, Director, Regulatory Affairs & Chris Buckley, Regulatory Affairs Associate Director at Astellas.


At its most basic level, increased document granularity within a submission simply means that there will be more documents to process and populate into a submission structure. More documents than what? - might be the next logical question. In the early years of electronic submissions most clinical study reports, were large and all inclusive of attachments and appendices. The drug product and drug substance documents were rolled up into complete files, respectively. Depending on the size of a study, a clinical study report document could exceed 100 MB in size and make the most confident publisher concerned about file corruption and poor performance. At that time, there were no requirements or expectations to sub-divide these documents into small defined granules by ICH or any regulatory authority.

Fast forward to the implementation of the Common Technical Document (CTD) and corresponding eCTD submission format that requires a greater degree of document granularity within a submission. With this emerging standard, the large documents needed to be authored as granular documents while still maintaining the overall content, research, and analysis of the entire topic (e.g. drug substance, drug product, clinical study). A benefit of the granulated approach is the ease of making changes or updates, review and approval, and lifecycle publishing of the granular document(s). On the publishing side, this concept eliminated the need to recreate bookmarks and hyperlinks in a large document and only perform these activities on the granular document(s). A challenge of maintaining granular documents is the need to conduct an impact analysis by the author and/or responsible department(s) to understand how a change to one granular document might impact other granular documents within the submission. A missing document in this analysis could result in an inconsistent message submitted to a regulatory authority, a problem that no sponsor company invites! Another challenge is maintaining the lifecycle links when certain destination documents are replaced or appended. Most current software cannot automatically update hyperlinks; therefore, potentially confusing the reviewer with outdated or broken links.

If you recall the basic concept of submission granularity of using a larger number of documents to create submissions, we have now complicated matters a bit. What was originally perceived as a submissions operations or publishing task is now an organizational, or at least a departmental process and/or strategy to develop granular content for submissions. It is not as simple as taking a large document and breaking it into smaller components. These components need to relate to each other and continue to provide continuity of the science and research of the submission application throughout its lifecycle. That is the entire organization’s responsibility, and not just the concern of the medical writing or publishing function. This change to a granular authoring approach may begin with the submissions operations or publishing group, but to successfully granulate documents the entire organization needs to be invested in developing granular content.

Source: GlobalSubmit Newsletter
http://globalsubmit.com