Transitioning from Paper to eCTD

In 2011, I wrote a guest post over at The eCTD Summit about transitioning from paper to eCTD submissions. Surprisingly, much of the advice in that post 6 years ago is still applicable, but the process is even easier today.

FDA’s deadline for converting marketing applications and master files to eCTD has passed, but you have until May 2018 to convert your commercial INDs. So, if you haven’t taken the plunge yet, here’s how.

The Process to Convert a Paper Application to eCTD

In the past, converting an IND from paper to eCTD began with a final paper submission notifying FDA of your intentions. Thankfully, this is no longer necessary. Today, you can convert your IND to eCTD without prior notification to FDA.

Your initial eCTD sequence should be simple – just a cover letter and a 1571. Your cover letter should note:

  • You are converting your application to eCTD format; and
  • All future submissions to this application will be in eCTD format.

This initial eCTD sequence should be coded as an Original Application in the regional metadata (even though it isn’t the actual original application submission). This is so that this conversion sequence can serve as the “anchor” for all future eCTD submissions to the IND.

With the successful completion of this submission, you are officially converted to eCTD!

Other Considerations

Using the Fillable FDA Form 1571

FDA requires that you submit the fillable version of the 1571. They use software to read the form and automatically route your submission appropriately upon receipt. FDA also encourages you to digitally sign this form. There are numerous ways you can accomplish this, including Adobe Acrobat’s built-in capability. If you are unable or unwilling to digitally sign the fillable form, you can use the following workaround:

  • Include the completed, unsigned fillable form in module 1.2; and
  • Include a signed, scanned version of the form in module 1.2.

Using this method, you provide both the required fillable form and the required signature. However, note that this option will likely be phased out in the near future. So, I encourage you to investigate and implement a digital signature option.

Resubmitting Information

A common question about the conversion from paper to eCTD is, “Do we need to resubmit everything we previously submitted in paper?” Thankfully, FDA does not require this. However, you may occasionally find it useful to “backfill” your eCTD application for the convenience of FDA reviewers.

For example, perhaps you’re submitting a protocol amendment as one of your first eCTD submissions, but the Investigator’s Brochure (IB) and the original protocol were submitted in paper. In the new eCTD sequence, you may want to include the IB and original protocol, just to make life easier for FDA reviewers. This will enable them to reference these documents in the eCTD instead of requesting the old paper files from the archives. I would apply a stamp to the IB and the original protocol, marking them as “Previously Submitted in Paper.” You should also explicitly mention them in the cover letter. Note that they:

  • were previously submitted in paper;
  • have not been changed from the versions previously submitted; and
  • are now being provided in the eCTD for the convenience of the reviewer.

This statement allows FDA reviewers to process your submission without re-reviewing these documents as if they were newly submitted information.

Sequence Numbering

According to FDA, you can start with sequence number 0000 or you can use any other sequence number. I recommend that you continue with the sequence numbering you’ve been using in your paper submissions. This will avoid the logistical complications that crop up when you restart the sequence numbering for your first eCTD submission. Your eCTD publishing software should allow you to change the sequence number from the default to any number.

There’s No Going Back

It’s important that you don’t view your conversion as a test drive. Once you convert your application to eCTD, you can’t decide to switch back to paper at a later date. Make sure that your entire team is on board and ready to make the transition before you pull the trigger.