Wednesday, June 28, 2023, was a significant day in the calendar for nonclinical data standardization with not one, but two new SEND Implementation Guides (IGs) plus their accompanying Conformance Rules. The new IGs were SENDIG-DART v1.2 and SENDIG-Genetox v1.0. I’ve discussed their content on the blog before, but now that both are published it’s worth taking a closer look and discussing their content.
Let’s start with the simpler of the two: SENDIG-Genetox v1.0. Although it was initially intended to include various in vitro and in vivo genetic toxicology tests, for practical reasons, it has been reduced to only cover subject-level in vivo micronucleus data and comet data from in vivo genetic toxicology studies. Originally planned to remain as a separate child IG, SENDIG-Genetox is now planned to be folded into the main SENDIG and future development of GeneTox for SEND would continue in the main IG, effectively orphaning SENDIG-Genetox once SEND v4.0 is published in a few years’ time.
Regardless of its future roadmap, let’s look at what makes up SENDIG-Genetox v1.0. It is a relatively small IG as it only contains a single domain: GV – Genetic Toxicology – In Vivo. The domain looks similar to the findings domains we are all accustomed to, particularly LB – Laboratory Results. There are no new variables, just the usual suspects of original results, standardized results, units, the typical timing variables, and the like. The IG is intended to be used in conjunction with the main SEND v3.1.1, effectively just providing us one more findings domain for micronucleus and comet assay data.
SENDIG-DART v1.2 is quite a different beast. It was created in direct response to the FDA’s study data Technical Conformance Guide (TCG) adding juvenile toxicology studies to the scope of SEND before any examples were available. Therefore SENDIG-DART v1.2 was quickly created to provide such examples. Effectively these studies look almost indistinguishable from regular general tox studies except that the data are analyzed by the postnatal day (PND i.e., the subject age) rather than the study day.
So SENDIG-DART v1.2 uses the existing domains, variables, and concepts to illustrate how to render a juvenile study in SEND. The only exception to this is the fact that we took the opportunity to add a new domain for developmental markers as, while not unique to these juvenile tox studies, they hold data relevant to understanding the safety implications of the compound on juveniles.
SENDIG-DART v1.2 was developed under this deliberately limited scope; however, it also addresses the key points coming out of the FDA’s recent fit-for-use pilot of SENDIG-DART v1.1. As such, it represents a significant improvement on SENDIG-DART v1.1, and while not changing any of the meaning or intention in that version, certainly makes for an IG that is easier to understand and implement as it removes much of the ambiguity that is present in v1.1.
Next time, I’ll be discussing the submission implications of these new IGs.
‘til next time,
Marc
