Some things I noticed right off the bat about differences with other guidance documents which are important:
• FDA says to provide a “scientifically justified rationale” if the CPCA is not met. However, they lack the clarity HC and EMA had.
o No mention on what to do with a negative Ames. They mention the EAT protocol, but what do you do with a negative? EMA and HC says TTC is appropriate.
o No mention of what to do with a negative in vivo study. EMA and HC says apply ICH Q3A/B.
o The read-across recommended is more restrictive, only limiting to what seams like a handful of compounds with robust data. Although in practice, other Health Authorities seem to be using a similar approach.
• Category 1 is 26.5 ng/day versus 18 ng/day (not particularly impactful but good to know)
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