Joel Finkle, Director Regulatory Innovation & IDMP Strategy
Note: This post appeared previously on LinkedIn.com
Some of you have been following my writing for a few years; I’ve got a new home at Acuta.
For others, this may be the first you’ve seen of my posts. I’ve been involved with electronic regulatory submissions since 1991 starting with document conversions for agencies and custom CANDAs (Computer Aided New Drug Applications), and struggled through the evolution of standardized PDF submissions through eCTD (electronic Common Technical Document), the development of RPS (Regulated Product Submissions – I’ll talk about that soon), and electronic drug registration processes from SPL (Structured Product Language), XEVMPD (Extended Eudravigilance Medicinal Product Dictionary) and IDMP (Identification of Medicinal Products). I’ve been on the industry side and as a vendor on the consulting, professional services, and software spaces.
For this debut post at Acuta, let’s look at the closest – and possibly most stressful – change: FDA is requiring that all marketing applications for drugs and biologics must be submitted in the eCTD format, starting May 5, 2017. This includes New Drug Applications (NDAs), Abbreviated NDAs (ANDAs) for generics, and Biological Licensing Applications (BLAs). An additional year is granted for Drug Master Files (DMFs), and Investigational New Drug (IND) filings, (May 5, 2018), and even then, only commercial INDs must comply – research institutes can, if they wish, continue to use a paper or PDF filing method.
This should not be a surprise: FDA set this in motion two years previously, on May 5 of 2015. For most companies, this will not be a difficult task because they’re already compliant. At the recent DIA RSIDM (Regulatory Submissions, Information, and Document Management) Forum in February 2017, Jonathan Resnick of FDA revealed that 99% of BLAs, and more than 95% of NDAs and ANDAs are already in eCTD format. INDs have held steady for several years at nearly 80%. The biggest trouble spot will likely be Drug Master Files, which have doubled their use of NDAs in the last four years from around 18% to 37%, but that’s a very long way from complete. That’s probably why DMF’s, which were supposed to go eCTD-only in 2017, were granted a year extension on that deadline, just in April of 2017.
It’s also a good idea from a financial standpoint: if a drug stands to make a billion dollars a year, every day it’s not on the market is nearly $3Million going to waste. eCTD-based submissions are immediately available to reviewers, compared to paper submissions which must be retrieved, one binder at a time, from agency archives. Following one reference from a summary to a clinical study report could put another day’s delay in the review.
So, what will it take to get compliant? Companies could use a text editor and an internet tool for generating checksums to create the XML ‘backbone’ which serves as the table of contents, but I wouldn’t recommend that for any but the simplest submissions, and by the sort of tech-savvy people who probably need to be doing more valuable work than that. I’ve done it, back before there were eCTD publishing systems, and it’s tedious and error-prone.
There is one tiny down side, though, to electronic submissions: a one-page change to a paper submission can be slipped into a binder in minutes (back in my days in pharma, we once had Regulatory Operations replacing pages in a moving semi-trailer to get it shipped out on time), whereas re-publishing a large submission and submitting to the agency could be many hours.
The next step up is to use a Regulatory Operations service organization, such as the Acuta Regulatory and Clinical Services (ARCS). Our services will include everything needed from cradle to grave including management of the submission planning process, compilation, validation to agency standards, and the actual electronic submission.
If you’d rather be more hands-on, Acuta’s ARIM (Acuta Regulatory Information Management) provides all the tools needed (it had better – it’s what ARCS uses on your behalf). ARIM can be configured as a cloud-based subscription to have you up and running quickly, or installed in your data center (although if you haven’t started planning for that, you’re probably a little late for any submissions that have to go in on May 5, 2017).
One other interesting detail: FDA has changed how the eCTD must be submitted. Originally, they only permitted physical media (overnight shipping a stack of CD-ROMs or a digital linear tape beat the heck out of using a that 18-wheel trailer of paper). They’ve since created the Electronic Submission Gateway, but have permitted CD’s, DVD’s and USB-based hard drives to continue to be submitted. At this point, they will require anything under 10GB of data to use the Gateway, and recommend that anything over 45GB use a USB drive instead of removable media.
For more information on how Acuta can get you ready for the eCTD mandate, contact us so we can get you up to date on technology and processes.