Responding to FDA Questions

Responding to FDA questions can be a challenge in the eCTD world. Companies often have a goal to respond to questions within a certain time frame. Short turnaround cycles force people to focus on content, and as a result, lifecycle management is often ignored. Over time this can lead to a messy submission with lots of appended information and orphaned responses. It's often challenging to figure out best practices under time pressure, so I've outlined some strategies to address this situation before it arises.


The problems with agency responses usually fall into 3 areas:

  • Updating portions of existing documents under deadline
  • Responding to a request for information that doesn't usually go into a submission
  • Balancing the often conflicting needs to answer the question and maintain clean document lifecycles

Updating Previously-Submitted Information

The first issue arises when the agency requests updates to information that's already been submitted. For example, the original submission contained a discussion of 3 month stability data and the agency wants an update with 6 month data. It's tempting, under deadline, to simply append the new information to the old, but this is penny wise and pound foolish. Authors and Regulatory professionals can be reluctant to replace what they've already submitted, preferring to append. Regulatory Operations often has to persuade them to take the time to update documents in order to use the Replace, rather than Append eCTD lifecycle operation. This is one of those situations where you have to convince people that you really are looking out for their long-term interests, and not trying to make their life difficult by insisting on process for the sake of process.

Sending Information That Isn't Normally Part of a Submission

Sometimes the agency requests information that wouldn't normally be included in a submission. For example, they may request SOPs related to cleaning-in-place procedures, but the company doesn't normally include SOPs in submissions. If you do submit them, you want them to stand apart from the submission, so that you're not setting a precedent, but still make it easy for the reviewers to find the information. In this case, I would include the information in module 1 and link to it from the cover letter. Putting the SOPs in module 3 suggests that's where they would normally go. Putting them in module 1 suggests they're part of a response to questions, not part of the normal submission.

Updating Information Separate From the Response

The third situation arises when you want to update certain information, such as the stability data in the first example, but also respond to the original question outside the normal eCTD structure. In this case, I recommend updating the stability information using the Replace lifecycle operation, and placing a response to questions document in module 1. It's important to explain what you did in the cover letter and include a link to the response document. You should also include links from the response document to the updated information in modules 2-5. This approach ensures that you've checked the box by responding to the question, and you've only included information in modules 2-5 that you want to be part of the ongoing record of that submission. In the future, people can refer back to module 1 to see the responses, but the key data has been included in the relevant technical sections following good document lifecycle practices. Ultimately, you can't control where the agency goes with their review, but you can control how you present and organize the information you submit.

When it comes to responding to agency questions, there is not a one-size-fits-all solution. Take advantage of the structure of the eCTD to organize your responses in a way that makes sense to you and will be easy to explain to your colleagues.