It was late 2020, during the FDA public webinar, as part of the CDISC face-to-face meeting, that the agency made the simplest of statements, which seemed to turn the world of SEND upside down:
“The placement of a study into the eCTD format does not determine the SEND requirement”
It was just one little line sitting innocuously amongst many others. Online chat lit up. For years, the CDISC fraternity had proclaimed the eCTD section, together with the study start date, as the key foundations for determining, absolutely, if a study required SEND datasets or not.
On that October morning, without fanfare or forewarning, the agency let us all know, that simply was not the case. What followed was a period of questions and honestly, confusion. Then, last week, the FDA’s Technical Conformance Guide v4.8 was published. Three additional pages of text were added under a new section called, “Scope of SEND”
Well, what does it say? It opens with the line, “The following is the Agency’s current thinking of the scope of SEND…”. So, everything stated is just the ‘current thinking’, and this target is moving.
It then broadly states that SEND datasets are required for as many studies as possible, an idea probably best captured in the line, “If the nonclinical pharmacology or toxicology study is required to support a regulatory decision by the Agency… then the nonclinical study would require SEND.”
Within this sweeping statement, the document then deals with some of the specifics, particularly focusing on areas that we’ve heard questioned over the past year. What happens when one study type incorporates endpoints from another study type? The document uses the example of general toxicity studies that incorporate cardiovascular safety pharmacology or genetic toxicity. It states that the study is still in scope for SEND with the expectation that any data which could be rendered in SEND, should be rendered in SEND.
The guide states that the age of the subject doesn’t impact the decision as to whether or not SEND is required. It states that SEND is required for juvenile studies as long as the study does not “…include multiple phases [which] cannot currently be modelled…”
It further states that, “The requirement for SEND is not limited to the drug substance” nor “…study report status or the finalization of the study report…” Also, regarding the GLP status “As both GLP and non-GLP toxicity studies may be submitted to the FDA to support clinical safety, the decision for inclusion of SEND is independent of GLP status.”
Over the course of three pages, the agency is attempting to be as clear and helpful as they can, to show that if a study can be rendered in SEND, for a study that informs the decision for the clinical safety of the drug, then those study data should be in SEND.
However, the text is littered with caveats and exceptions, and so appears both explicit and vague at the same time. For this reason, it encourages sponsors to enter into “discussion with the review division when there is any ambiguity on the SEND requirement…”. We have to appreciate that this is an effort to clarify the expectations, and though it seems to leave many questions unanswered, one thing is certain, they are encouraging the submission of SEND datasets.
So, does your study require SEND? That question just got a whole lot harder to answer, but certainly the answer is now more likely to be, “Yes.”
Till next time,
Marc
