How to avoid rejection

It’s a basic human need: We want our work accepted and valued. Nobody wants to see their work rejected. It’s so obvious, it almost goes without saying. Worse still would be being rejected by a cold, heartless automated computerized system. That would be soul destroying. However, with the FDA’s latest deadline, automated rejections will start to occur.

In this post I’d like to discuss how to avoid rejection of your electronic study data – especially since we are less than two months (September 15, 2021) away from the enforcement of the Technical Rejection Criteria (TRC).

Up to now, failure of the TRC has not resulted in rejection, but instead FDA have simply issued warnings alerting the submitting sponsor to the issue. At the FDA’s recent SBIA (Small Business Industry Assistance) webcast, the agency presented data showing over 200 studies had been issued with such warnings in a single month (March 15, 2021, to April 17, 2021). From September, all such studies would result in a rejection instead of a warning.

I’ve included a link to the TRC at the end of this post and at first look, the rules can seem quite complicated. There’s mention of a TS domain, certain eCTD sections where the TRC does not apply, discussion about the study tagging file and so on.

At Instem, we are well versed in helping our customers navigate the intricacies of the TRC, and for certain studies, this can get quite complicated, however, in its simplest form, the principle is first to check if the eCTD section is applicable, and then to check the study start date.

Certain sections of the eCTD are exempt from TRC. These sections are listed in the TRC so we can easily check if a particular study would be exempt. If the study is to be placed in an applicable section, then the next things to consider are the study start date, submission type and study type.

For an IND submission:

• Single Dose Toxicity, Repeat Dose Toxicity, and Carcinogenicity Studies starting after December 16, 2017 require a full SEND package
• Cardiovascular and Respiratory Safety Pharmacology Studies starting after March 15, 2020 also require a full SEND package.

The NDA/BLA requirement is exactly the same as IND, expect in each case it is a year earlier, so December 16, 2016, for Repeat Dose Toxicity, for example.

However, even if the study starts before these dates, it is still not fully exempt if it still falls in the appropriate eCTD section. In that case, a ‘Simplified ts.xpt’ file is still required. This is an electronic data file stating the Study ID and the start date. While not a SEND file itself, it’s format generally follows the SEND standard for the TS domain, albeit with just a single record.

As I said when I started this post, nobody likes being rejected, so it’s vital that sponsors understand the TRC requirement as it becomes enforced in September. The TRC is just the first step in the process employed by the agency in ensuring they are receiving good quality, usable SEND datasets. Maybe in a future post we can discuss some of the further measures they employ.

Till next time,

Marc

Access the full TRC here: https://www.fda.gov/media/100743/download