Have you heard of ICH S1B (R1)? It’s not currently causing too many waves in the world of SEND, but maybe it should. S1B hasn’t really landed on the SEND horizon yet, so you’d be forgiven for not being fully up to speed with it. Let me give you the 101:
This guideline was finalised in 2022 and it aims to remove unnecessary animal testing, specifically the two-year rat carcinogenicity test, for small molecules. Ultimately, companies can save money and time without compromising patient safety. Win, win and win.
If there’s evidence that a two-year rat carcinogenicity test wouldn’t add value, that evidence can be submitted to regulatory authorities, who will decide if the compound can move forward without it. This submission, called a “weight of evidence,” should address six factors outlined in the ICH S1B guideline:
- Target Biology
- Secondary Pharmacology
- Histopathology
- Hormonal Effects
- Genotoxicity
- Immune Modulation
At this point, you may be able to see where I’m going. Four of these factors involve data that may be present in SEND data prepared for other studies for this compound.
For Histopathology, the guideline specifically calls out a list of histopathology findings as being indicators to include in our S1B Weight of Evidence, such as cellular hypertrophy and cellular hyperplasia. We could easily use our SEND data here.
For the Hormonal Effects, the guideline states we are looking for microscopic changes in endocrine or reproductive tissues and “Biologically significant endocrine and reproductive organ weight changes.”
Again, we can easily search our SEND datasets for these findings. When it comes to organ weight changes, we could do this using SEND, as SEND has all of the weight data, however, it doesn’t list changes in weight, it simply lists the weights recorded. So, we could use the SEND data to run a comparison of the treated subjects against the organ weights of the control subjects, and then see if any changes are biologically significant. We could do that. Or, we could just read the conclusion in the report. We’d probably be better served by just looking in the report. However, if we wanted to include any of the raw data, then we could easily extract those data points from SEND. For Genotoxicity, well this is an area that is relatively new to SEND, as the FDA requirement only kicks in from March next year, so it’s probably unlikely that we have SEND datasets to exploit at the moment. But give it time.
And finally, to Immune Modulation, where the guide uses the term “broad immunosuppression“. To paraphrase the FDA’s Study Data Technical Conformance Guide, Immune results do not have a dedicated domain yet in SEND, but they can be force fit either into the LB – Laboratory Results domain or into a custom IS – Immune System domain. So, if immune data were collected on our study, then they should be present in either LB or IS. But due to this force fitting, this may not be done in a consistent manner. Which certainly impairs any automated searching.
The ICH S1B guidance is making significant ripples across our industry, potentially saving years of effort in the development of a new drug, and SEND can certainly play its part in enabling this. If you are interested in discovering more about this topic, and you are attending this year’s ACT (American College of Toxicology) meeting in Austin, Texas, I will be presenting a deep dive into this subject there, with my partner in crime, Dr Frances Hall. Stop by booth #306 to chat with us and get more info on this presentation.
‘til next time
Marc
