In my last blog post, I described the content of the two new implementation guides (IGs) that CDISC has just published as part of the SEND standard. These are the SENDIG-Genetox v1.0 and SENDIG-DART v1.2. In this post we’ll discuss the submission implications of the publication of these new IGs. I should caveat this by saying that these are just my interpretations of the FDA submission requirements and I certainly don’t speak on behalf of the agency.
I’m sure we are all aware that the CDISC publication of a standard and FDA requirement are separate. For a new standard, which I believe is the case for SENDIG-Genetox, the industry would have a minimum of two years to implement the standard, starting from the following March. This means that while the agency may appreciate receiving SENDIG-Genetox datasets ahead of time, the earliest we can expect this standard to become a regulatory requirement would be for studies starting March 2026. As described previously, SENDIG-Genetox needs to be used in conjunction with SEND v3.1.1. So, while SEND v3.1.1 has been around for some time, the requirement for the relevant genetic toxicology data wouldn’t be required until 2026.
The picture for SENDIG-DART v1.2 is slightly different. Firstly, this is an update to an existing standard that is already required, and as such, the earliest that v1.2 could be required would be for studies starting March 2025. Secondly, this update is to address a requirement that has already been present in the FDA’s study data Technical Conformance Guide (TCG) for some time. The update demonstrates how to represent data for a juvenile toxicology study that reports by post-natal day (i.e. the age of the subject) rather than by study day. However, I still receive plenty of questions about juvenile studies and SEND, as this complexity isn’t well understood. My simple explanation is that the juvenile studies described in the TCG relate to repeat dose general toxicology studies conducted using younger subjects, and as such:
- If the juvenile study doesn’t include reproductive phases, and is reported by study day, then SEND v3.1 or SEND v3.1.1 can be used.
- If the juvenile study doesn’t include reproductive phases and is reported by post-natal day, then the study can be represented in SENDIG-DART v1.2.
- If the study does include reproductive phases, then it has not yet been modeled in SEND and would be out of scope.
One further complication to this is when the study contains neurobehavior endpoints. CDISC has long had a domain in development to represent these data, however, it has not yet been published. It is called the NV domain and will arrive as part of SEND v4.0; so, currently, it is out of scope. These data could be represented in a custom domain for NV, but technically out of scope.
At the point that SEND 4.0 is published, SENDIG-DART v1.2 could well be required but based on SENDIG 3.1.1, not SEND 4.0. Therefore, we could have our juvenile studies, reported by post-natal day, required for all except the neurobehavior endpoints, even though the NV domain is already published. Again, an NV domain could be supplied, but it would need to be a custom domain.
So, for SENDIG-Genetox, we press on with implementation, on our way to an expected March 2026 requirement. For juvenile studies, we need to consider if this is a study that can be represented in SEND 3.1.1 or if it really needs SENDIG-DART 1.2.
‘til next time
Marc
